Solid dispersion of compound having p2x4 receptor antagonist

Abstract

The present invention provides a solid dispersion containing a compound represented by general formula (I) or (II), or a pharmacologically acceptable salt thereof.

Description

Technical Field

[0001] The present invention relates to a solid dispersion containing a compound represented by the general formula (I) or (II) described below (hereinafter referred to as the "present compound") or a pharmaceutically acceptable salt thereof, which has a strong P2X4 receptor antagonist effect. This application claims priority based on Japanese Patent Application No. 2023-26977 filed in Japan on February 24, 2022, and the contents of which are incorporated herein by reference. Background Art

[0002] ATP receptors are broadly divided into the P2X family of ion channel receptors and the P2Y family of G protein-coupled receptors, and seven (P2X1-7) and eight (P2Y1, 2, 4, 6, 11-14) subtypes have been reported so far, respectively.

[0003] The P2X4 receptor (Genebank No. X87763), which is a subtype of the P2X family, has been reported to be widely expressed in the central nervous system and the like (Non-Patent Documents 1 to 5).

[0004] The exact pathogenesis of chronic or intractable pain, typified by neuropathic pain, remains unclear, and treatment remains unresolved, often with the ineffectiveness of nonsteroidal anti-inflammatory drugs (NSAIDs) and morphine. Consequently, this places a heavy physical and mental burden on patients and their families. Neuropathic pain is often caused by damage to the peripheral or central nervous system, such as postoperative complications, cancer, spinal cord injury, herpes zoster, diabetic neuritis, and trigeminal neuralgia.

[0005] The present inventors have discovered the present compounds as P2X4 receptor antagonists and filed a patent application (Patent Document 1). These compounds are useful as therapeutic agents for neuropathic pain, multiple sclerosis, cough suppression, irritable bowel syndrome, inflammatory bowel disease, various allergies, and the like (Patent Documents 2-6).

[0006] The present inventors have studied the compound disclosed in Patent Document 1 and have found that the compound is poorly water-soluble and that there is room for improvement in its in vivo absorbability when orally administered.

[0007] Methods for improving the in vivo absorbability of poorly soluble compounds include methods for micronizing poorly soluble compounds and methods for preparing solid dispersions. For example, Patent Document 7 discloses a method for finely crystallizing istradefylline, and Patent Document 8 discloses a method for preparing a solid dispersion of a thiazolopyrimidine derivative and a hydroxypropyl methylcellulose derivative. In order to improve the in vivo absorbability of poorly soluble compounds by preparing solid dispersions, the poorly soluble compounds need to be made amorphous. However, the amorphous state is generally unstable to water. By combining the poorly soluble compound with a polymer, the poorly soluble compound will transform from amorphous to crystalline during long-term storage. Therefore, there is a problem that a certain solubility cannot be obtained over time (Non-Patent Documents 6 to 8).

[0008] Prior art literature

[0009] Patent Literature

[0010] Patent Document 1: International Publication No. 2013 / 105608

[0011] Patent Document 2: International Publication No. 2017 / 188365

[0012] Patent Document 3: International Publication No. 2019 / 177117

[0013] Patent Document 4: International Publication No. 2020 / 050253

[0014] Patent Document 5: International Publication No. 2021 / 198745

[0015] Patent Document 6: International Publication No. 2022 / 030428

[0016] Patent Document 7: International Publication No. 2004 / 099207

[0017] Patent Document 8: International Publication No. 2019 / 107412

[0018] Non-patent literature

[0019] Non-patent document 1: Buell et al. (1996) EMBO J. 15: 55-62

[0020] Non-patent document 2: Seguela et al. (1996) J. Neurosci. 16: 448-455

[0021] Non-patent document 3: Bo et al. (1995) FEBS Lett. 375: 129-133

[0022] Non-patent document 4: Soto et al. (1996) Proc Natl. Acad. Sci. USA 93: 3684-3788

[0023] Non-patent document 5: Wang et al. (1996) Biochem. Res. Commun. 220: 196-202

[0024] Non-patent document 6: Shibata Y. Yakuzaigaku., 71(1), 50-54 (2011)

[0025] Non-patent document 7: Imaizumi H. Chem. Pharm. Bull., 31, 2510-2512 (1983)

[0026] Non-patent document 8: Konno H. Yakuzaigaku., 71(2), 109-113 (2011) Summary of the Invention

[0027] The present invention aims to improve the in vivo absorbability of the present compound or a pharmaceutically acceptable salt thereof disclosed in Patent Document 1 and to provide a pharmaceutical composition as a solid dispersion containing the compound or a pharmaceutically acceptable salt thereof as an active ingredient.

[0028] The present inventors have conducted various studies on improving the absorbability of the present compound or a pharmaceutically acceptable salt thereof disclosed in Patent Document 1 and have found that in vivo absorbability can be improved by forming a solid dispersion with a specific polymer or the like, thereby completing the present invention.

[0029] That is, the present invention has the following aspects.

[0030] [1] A solid dispersion comprising a compound represented by the following general formula (I) or (II), or a pharmacologically acceptable salt thereof.

[0031]

[0032] (Where R 1 and R 2and alkyl and alkyl groups 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 by 1 to 3 halogen atoms, an alkoxy group having 1 to 8 carbon atoms substituted by 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),

[0033] or

[0034] R 1 and R 2 Together with the benzene ring to which they are bonded, they can form a condensed 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 1 and R 2 Together and R 1 and R 2 The ring composed of the carbon atoms to which the respective bonds are attached may be substituted by 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 by 1 to 3 halogen atoms, an alkoxy group having 1 to 8 carbon atoms substituted by 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).

[0035] R 3 and R 4 and 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 by 1 to 3 halogen atoms, an alkoxy group having 1 to 8 carbon atoms substituted by 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),

[0036] R 5 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 moiety has 6 to 10 carbon atoms and the alkylene moiety has 1 to 8 carbon atoms),

[0037] R 6 and R 7 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 by 1 to 3 halogen atoms, an alkoxy group having 1 to 8 carbon atoms substituted by 1 to 3 halogen atoms, a halogen atom, a hydroxyl group or an amino group,

[0038] X represents C, CH or N,

[0039] Y represents N, NH or C(=O),

[0040] Among them, when X is N, Y is not N or NH,

[0041] In addition, when X is C or CH, and Y is not C(=O),

[0042] A double line consisting of a solid line and a dashed line represents a single bond or a double bond.

[0043] Z represents an oxygen atom or a sulfur atom,

[0044] A represents a benzene ring which may have 1 to 4 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 aralkyl group (the aryl moiety has 6 to 10 carbon atoms and the alkylene moiety has 1 to 8 carbon atoms), a phenyl ring, a pyridine ring, a thiophene ring, a pyrimidine ring, a naphthalene ring, a quinoline ring, or an indole ring, or represents a bonding site,

[0045] B represents N(R 8 )C(=O)、NHCONH、CON(R 9 )、NHC(=S)NH、N(R 10 )SO2、SO2N(R 11 ) or OSO2,

[0046] Here, R 8 、R 9、R 10 and R 11 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 hydroxy group, or an aralkyl group (the aryl moiety has 6 to 10 carbon atoms and the alkylene moiety has 1 to 8 carbon atoms),

[0047] D represents an alkylene chain having 1 to 6 carbon atoms which may have 1 to 4 substituents 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 or an aralkyl group having 1 to 8 carbon atoms substituted with a hydroxy group (the aryl moiety has 6 to 10 carbon atoms and the alkylene moiety has 1 to 8 carbon atoms), which may be the same or different, and further represents a bonding site,

[0048] E stands for O, S, NR 12 , or bonding sites,

[0049] Here, R 12 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 moiety has 6 to 10 carbon atoms and the alkylene moiety has 1 to 8 carbon atoms),

[0050] G represents an optionally substituted 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 (the aryl moiety has 6 to 10 carbon atoms and the alkylene moiety has 1 to 8 carbon atoms), an optionally substituted phenyl group, an optionally substituted pyridyl group, an optionally substituted imidazolyl group, an optionally substituted oxazolyl, or the same or different substituents in the thiazolyl group which may have a substituent as a substituent, piperazine, piperidine, morpholine, cyclohexane, benzene, naphthalene, quinoline, quinoxaline, benzimidazole, thiophene, imidazole, thiazole, azole, indole, benzofuran, pyrrole, pyridine or pyrimidine,

[0051] Furthermore, m represents an integer of 0-5.

[0052] The following situations are not included:

[0053] R 1 and R 2 When they do not form a ring together, X is C, Y is N, the double line composed of solid and dashed lines is a double bond, Z is an oxygen atom, A is a benzene ring, m is 0, B is C(=O)NH, E is a bonding site, and G is a phenyl group;

[0054] R 1 、R 2 、R 4 、R 5 、R 6 and R 7 is a hydrogen atom, R 3 is a chlorine atom, X is C, Y is N, the double line consisting of a solid line and a dashed line is a double bond, Z is an oxygen atom, A is a bonding site, m is 1, B is NHC(=O), D is a methylene group or a bonding site, E is a bonding site, and G is a phenyl group; and

[0055] R 1 、R 2 、R 3 、R 4 、R 5 、R 6 and R 7 is a hydrogen atom, X is N, Y is C(=O), the double line consisting of a solid line and a dotted line is a single bond, Z is an oxygen atom, A is a bonding site, m is 1, and B is CON(R 9 ), R 9 isopropyl, E is a bonding site, and G is a phenyl group which may be substituted by a methoxy group.

[0056]

[0057] (Where,

[0058] represents a naphthalene ring, a quinoline ring, an isoquinoline ring, a tetrahydronaphthalene ring, an indane ring, a tetrahydroquinoline ring or a tetrahydroisoquinoline ring,

[0059] 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).

[0060] R 3a and R 4a and 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 by 1 to 3 halogen atoms, an alkoxy group having 1 to 8 carbon atoms substituted by 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),

[0061] R 5a 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 moiety has 6 to 10 carbon atoms and the alkylene moiety has 1 to 8 carbon atoms),

[0062] R 6a and R 7a 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 by 1 to 3 halogen atoms, an alkoxy group having 1 to 8 carbon atoms substituted by 1 to 3 halogen atoms, a halogen atom, a hydroxyl group, or an amino group,

[0063] represents a benzene ring, pyridine ring, thiophene ring, pyrimidine ring, naphthalene ring, quinoline ring, or indole ring which may have 1 to 4 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 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 which may have the same or different substituents as a substituent, or represents a bonding site,

[0064] B a N(R 8a )C(=O)、NHCONH、CON(R 9a )、NHC(=S)NH、N(R 10a )SO2、SO2N(R 11a), or OSO2,

[0065] Here, R 8a 、R 9a 、R 10a and R 11a 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 hydroxy group, or an aralkyl group (the aryl moiety has 6 to 10 carbon atoms and the alkylene moiety has 1 to 8 carbon atoms),

[0066] E a Indicates O, S, NR 12a or bonding sites,

[0067] Here, R 12a 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 moiety has 6 to 10 carbon atoms and the alkylene moiety has 1 to 8 carbon atoms),

[0068] G a represents a group which may have 1 to 4 groups 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, an alkylsulfonyl group having 1 to 6 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 which may have a substituent, a pyridyl group which may have a substituent, an imidazolyl group which may have a substituent, and an oxazolyl, or the same or different substituents in the thiazolyl group which may have a substituent as a substituent, piperazine, piperidine, morpholine, cyclohexane, benzene, naphthalene, quinoline, quinoxaline, benzimidazole, thiophene, imidazole, thiazole, azole, indole, benzofuran, pyrrole, pyridine or pyrimidine,

[0069] Furthermore, n represents an integer from 0 to 5.)

[0070] [2] The solid dispersion according to item [1], comprising a combination of hydroxypropyl methylcellulose (HPMC) and sodium lauryl sulfate (SLS), or aminoalkyl methacrylate copolymer E.

[0071] [3] The solid dispersion according to item [2], comprising a combination of hydroxypropyl methylcellulose (HPMC) and sodium lauryl sulfate (SLS).

[0072] [4] The solid dispersion according to any one of items [1] to [3], wherein the compound is B a It is an NHCO group or NHSO2 group bonded to the 3rd or 4th position of the benzene ring, n is 0 to 2, E a is the bonding site, G a A compound represented by the above general formula (II) which is a substituted phenyl group or pyridyl group.

[0073] [5] The solid dispersion according to any one of items [1] to [4], wherein B a is an NHCO group bonded to the 4-position of the benzene ring, n is 0, G a is a substituted phenyl group.

[0074] [6] The solid dispersion according to any one of items [1] to [5], wherein G a is a trifluoromethyl group, a hydroxyl group, an alkyl group, or a halogen atom, G a is a substituted phenyl group.

[0075] [7] The solid dispersion according to any one of items [1] to [3], wherein the compound or a pharmacologically acceptable salt thereof is selected from the following (1) to (214):

[0076] (1) 5-(4-Benzoylaminophenyl)-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0077] (2) 5-[4-[(2-(trifluoromethyl)benzoyl]aminophenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0078] (3) 5-[4-(3-bromobenzoyl)aminophenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0079] (4) 5-[4-[4-(trifluoromethyl)benzoyl]aminophenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0080] (5) 5-[4-(2-methylbenzoyl)aminophenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0081] (6) 5-[4-(2,6-dimethylbenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0082] (7) 5-[4-(2,6-dichlorobenzoyl)aminophenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0083] (8) 5-[4-(3-chlorobenzoyl)aminophenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0084] (9) 5[4-(2-phenylacetylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0085] (10) 1-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-amino)phenyl]-3-phenylthiourea;

[0086] (11) 5-[4-(2,3-dimethoxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0087] (12) 5-[4-(2-methoxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0088] (13) 5-[4-[(2-chlorophenylacetyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0089] (14) 5-[4-(2,3-dimethylbenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0090] (15) 5-[4-(2,5-dimethylbenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0091] (16) 5-[4-(5-bromo-2-chlorobenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0092] (17) 5-[4-(2,4-dichlorobenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0093] (18) 5-[4-(2-hydroxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0094] (19) 5-[4-(2,3-dihydroxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0095] (20) 1-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-amino)phenyl]-3-phenylurea;

[0096] (21) 5-[4-[(2,6-dichlorophenylacetyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0097] (22) 5-[4-[(2-methoxyphenylacetyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0098] (23) 5-[4-[(2-hydroxyphenylacetyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0099] (24) 1-(2-chlorophenyl)-3-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-amino)phenyl]thiourea;

[0100] (25) 5-[4-[3-(trifluoromethyl)benzoylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0101] (26) 5-[4-[2-[(2-trifluoromethyl)phenyl]acetylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0102] (27) 1-(2-chlorophenyl)-3-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-amino)phenyl]urea;

[0103] (28) 5-[4-[(2-phenylpropionyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0104] (29) 5-[4-(2-chloro-3-methoxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0105] (30) 5-[4-(3-phenylpropionylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0106] (31) 5-[4-[(1H-indole-3-carbonyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0107] (32) 5-[4-(2-chloro-3-hydroxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0108] (33) 5-[4-[(2-methyl-2-phenylpropionyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0109] (34) 5-[4-(2-phenoxyacetylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0110] (35) 5-[4-[2-(2-chloro-4-methoxyphenyl)acetylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0111] (36) 5-[4-[(1-methyl-1H-imidazole-2-carbonyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0112] (37) 5-[4-[2-(2,4-dichlorophenyl)acetylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0113] (38) 5-[4-[2-(2-chloro-4-hydroxyphenyl)acetylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0114] (39) 5-[4-(3-phenylpropenylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0115] (40) 5-[4-[(3-pyridylacetyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-diketone hydrochloride;

[0116] (41) 5-[4-(1H-benzimidazole-2-carbonylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0117] (42) 1-[4-(2,3-dimethylbenzoylamino)phenyl]-7-methoxy-1H-1,5-benzodiazepine -2,4(3H,5H)-dione;

[0118] (43) 5-[4-[(Benzoylamino)methyl]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0119] (44) 5-[4-[(2-chlorobenzoylamino)methyl]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0120] (45) 1-[4-(2,3-dimethylbenzoylamino)phenyl]-7-hydroxy-1H-1,5-benzodiazepine -2,4(3H,5H)-dione;

[0121] (46) 5-[4-(2-chlorobenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0122] (47) 5-[4-(2-bromobenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0123] (48) 5-[4-(2-iodobenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0124] (49) 5-[4-(2,3-dimethylbenzoylamino)-3-fluorophenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0125] (50) 5-[4-[2-(2-methylphenyl)acetylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0126] (51) 5-[4-[(quinoxalin-2-yl)carbonylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0127] (52) 5-[4-[(5-methylthiophen-2-yl)carbonylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0128] (53) 5-[3-[(2-chlorophenylacetyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0129] (54) 5-[4-[(2,4,6-trimethylbenzoyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0130] (55) 5-[4-(cyclohexylcarbonylamino)phenyl]-1,2,3,4,8,9,10,11-octahydronaphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0131] (56) 1-[4-(2,3-dimethylbenzoyl)aminophenyl]-6-methyl-1H-1,5-benzodiazepine -2,4(3H,5H)-dione;

[0132] (57) 5-[4-[(2-ethylbenzoyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0133] (58) 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;

[0134] (59) 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;

[0135] (60) 1-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-amino)phenyl]-3-(2-methylphenyl)thiourea;

[0136] (61) 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;

[0137] (62) 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;

[0138] (63) 5-[4-(2,3-dimethylbenzoylamino)-3-hydroxyphenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0139] (64) 5-[4-(2-chloro-3-methoxybenzoylamino)phenyl]-1,3-dihydronaphtho[1,2-e]-1,4-diazepine -2-ketone;

[0140] (65) 5-[4-[(4-dimethylaminobenzoyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0141] (66) 5-[4-[2-(2,4-dichlorophenoxy)acetylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0142] (67) 5-[4-[2-(2-methylphenoxy)acetylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0143] (68) N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-yl)butyl]-2-chloro-3-methoxybenzamide;

[0144] (69) 5-[4-(2-chloro-3-hydroxybenzoylamino)phenyl]-1,3-dihydronaphtho[1,2-e]-1,4-diazepine -2-ketone;

[0145] (70) 5-[4-(2-acetylbenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0146] (71) 5-[4-(2-tert-butylbenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0147] (72) 5-[2-(2-iodobenzoyl)aminoethyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0148] (73) 5-[3-[(2-iodobenzoyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0149] (74) 6,7-dimethyl-1-[4-(2-iodobenzoyl)aminophenyl]-1H-1,5-benzodiazepine -2,4(3H,5H)-dione;

[0150] (75) 5-[4-[(1-methylpiperidin-4-yl)carbonylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-diketone hydrochloride;

[0151] (76) 5[4-[(Benzofuran-2-yl)carbonylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0152] (77) 5-[4-[(1-methyl-1H-indol-3-yl)carbonylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0153] (78) 5-[4-(2-propenylbenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0154] (79) 5-[4-(2-propylbenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0155] (80) 5-[3-fluoro-4-(2-iodobenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0156] (81) 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;

[0157] (82) 5-[4-[(2-isopropoxybenzoyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0158] (83) 5-[4-[(3-methylthiophen-2-yl)carbonylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0159] (84) 5-[4-(2-phenoxypropionylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0160] (85) 5-[4-[2-(4-chloro-2-methylphenoxy)acetylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0161] (86) 5-[4-(4-fluoro-2-trifluoromethylbenzoyl)aminophenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0162] (87) 5-[4-(4-fluoro-2-methoxybenzoyl)aminophenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0163] (88) 5-[4-(4-fluoro-2-hydroxybenzoyl)aminophenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0164] (89) 5-[3-[(2-iodophenylacetyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0165] (90) 5-[4-(2-methyl-2-phenoxypropionylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0166] (91) 5-[4-(2-tert-butylbenzoylamino)phenyl]-1,3-dihydronaphtho[1,2-e]-1,4-diazepine -2-ketone;

[0167] (92) 5-[4-[(3-dimethylaminobenzoyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0168] (93) 5-[4-(4-iodo-2-methoxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0169] (94) 5-[4-(6-fluoro-2-methoxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0170] (95) 5-[4-(2-hydroxy-4-iodobenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0171] (96) 5-[4-(6-fluoro-2-hydroxyamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0172] (97) 5-[4-(2-fluorobenzoyl)aminophenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0173] (98) 5-[4-[(2-dimethylaminobenzoyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0174] (99) 5-[4-(2-methoxy-6-methylbenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0175] (100) 5-[4-(2-hydroxy-6-methylbenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0176] (101) 5-[4-[3-(2-methylphenyl)propionylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0177] (102) 5-(4-phenylcarbamoylphenyl)-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0178] (103) 5-(4-Benzylcarbamoylphenyl)-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0179] (104) 5-[4-[3-(2-methylphenyl)acryloylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0180] (105) 5-[4-[3-(2-chlorophenyl)propionylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0181] (106) 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;

[0182] (107) 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;

[0183] (108) 5-[4-(2-chlorobenzyl)carbamoylphenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0184] (109) 5-[4-[3-(2-chlorophenyl)acryloylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0185] (110) 5-[4-(2-chlorophenyl)carbamoylphenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0186] (111) 5-[4-(6-bromo-2,3-methylenedioxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0187] (112) 5-[4-(6-bromo-2-methoxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0188] (113) 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;

[0189] (114) 5-[2-(2-iodobenzoyl)aminopyridin-5-yl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0190] (115) 5-[4-(6-bromo-2-hydroxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0191] (116) 5-[4-(6-chloro-2-methoxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0192] (117) 5-[4-(2-iodobenzoylamino)phenyl]-1H-[1,4]diazepine 2,3-h]quinoline-2,4(3H,5H)-dione;

[0193] (118) 5-[4-(6-chloro-2-hydroxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0194] (119) 5-[4-(2-hydroxy-6-methoxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0195] (120) 5-[4-[2-methoxy-6-(trifluoromethyl)benzoylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0196] (121) 5-[4-[2-hydroxy-6-(trifluoromethyl)benzoylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0197] (122) 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;

[0198] (123) 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;

[0199] (124) 5-[4-[2-chloro-5-(methylthio)benzoylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0200] (125) 5-[4-[2-(methylthio)benzoylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0201] (126) 5-[4-[3-(methylthio)benzoylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0202] (127) 5-[4-[2-ethyl-6-methoxybenzoylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0203] (128) 5-[4-(3-methylsulfonylbenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0204] (129) 6-ethyl-1-[4-(2-iodobenzoyl)aminophenyl]-1H-1,5-benzodiazepine -2,4(3H,5H)-dione;

[0205] (130) 5-[4-[2-ethyl-6-hydroxybenzoylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0206] (131) 5-[4-(3-methanesulfinylbenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0207] (132) 5-[4-(2-chloro-5-methanesulfinylbenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0208] (133) 5-[4-(2-methanesulfinylbenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0209] (134) 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)-diketone hydrochloride;

[0210] (135) 5-[4-(2-chloro-6-methoxybenzoylamino)phenyl]-1,3-dihydronaphtho[1,2-e]-1,4-diazepine -2-ketone;

[0211] (136) 5-[4-[[(3-chloropyridin-2-yl)carbonyl]amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0212] (137) 5-[4-(2-chloro-6-hydroxybenzoylamino)phenyl]-1,3-dihydronaphtho[1,2-e]-1,4-diazepine -2-ketone;

[0213] (138) 5-[4-(3-chloro-2-methoxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0214] (139) 5-[4-[(3-methylpyridin-2-yl)carbonylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0215] (140) 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;

[0216] (141) 5-[4-(3-chloro-2-hydroxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0217] (142) 5-[4-[[(3-hydroxypyridin-2-yl)carbonyl]amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0218] (143) 5-[4-[(3-vinylpyridin-2-yl)carbonylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0219] (144) 5-[4-[(3-ethylpyridin-2-yl)carbonylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0220] (145) N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho-[1,2-b][1,4]-diazepine -5-amino)phenyl]-2-nitrobenzenesulfonamide;

[0221] (146) N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-amino)phenyl]benzenesulfonamide;

[0222] (147) 3-Bromo-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-amino)phenyl]benzenesulfonamide;

[0223] (148) N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-amino)phenyl]-3-methoxybenzenesulfonamide;

[0224] (149) N-[3-(2-oxo-2,3-dihydro-1H-naphtho[1,2-e][1,4]diazepine -5-amino)phenyl]benzenesulfonamide;

[0225] (150)N-[3-(2,4-dioxo-1,2,3,4-tetrahydronaphtho-[1,2-b][1,4]-diazepine -5-amino)phenyl]-2-nitrobenzenesulfonamide;

[0226] (151)N-[4-(2,4-dioxo-1,2,3,4,8,9,10,11-octahydro-naphtho[1,2-b][1,4]-diazepine -5-amino)phenyl]-2-nitro-benzenesulfonamide;

[0227] (152) N-[4-(2,4-dioxo-1,2,3,4,8,9,10,11-octahydro-naphtho[1,2-b][1,4]-diazepine -5-amino)phenyl]-N-methyl-2-nitrobenzenesulfonamide;

[0228] (153)N-[3-(2,4-dioxo-1,2,3,4-tetrahydronaphtho-[1,2-b][1,4]-diazepine -5-amino)phenyl]-N-methyl-2-nitrobenzenesulfonamide;

[0229] (154) 4-(2,4-dioxo-1,2,3,4,8,9,10,11-octahydronaphtho[1,2-b][1,4]diazepine -5-yl)-N-phenylbenzenesulfonamide;

[0230] (155)N-[3-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b]-[1,4]diazepine -5-yl)phenyl]-2-naphthalenesulfonamide;

[0231] (156) N-[3-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b]-[1,4]diazepine -5-yl)phenyl]-1-naphthalenesulfonamide;

[0232] (157) N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-amino)phenyl]cyclohexanesulfonamide;

[0233] (158) N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-amino)phenyl]-3-pyridinesulfonamide hydrochloride;

[0234] (159)N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-amino)phenyl]-4-isopropylbenzenesulfonamide;

[0235] (160)N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-amino)phenyl]phenylmethanesulfonamide;

[0236] (161)N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-yl)phenyl]-3-pyridinesulfonamide;

[0237] (162) N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-yl)phenyl]-2-naphthalenesulfonamide;

[0238] (163) 4-(2,4-dioxo-1,2,3,4,8,9,10,11-octahydronaphtho-[1,2-b][1,4]diazepine -5-yl)phenyl 3-bromobenzenesulfonate;

[0239] (164) N-benzyl-N-[4-(1-benzyl-2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-amino)phenyl]-2-nitrobenzenesulfonamide;

[0240] (165) N-benzyl-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-amino)phenyl]-2-nitrobenzenesulfonamide;

[0241] (166) 3-Bromo-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-yl)phenyl]-N-methylbenzenesulfonamide;

[0242] (167) N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho-[1,2-b][1,4]-diazepine -5-amino)phenyl]-N-methyl-2-nitrobenzenesulfonamide;

[0243] (168) N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho-[1,2-b][1,4]-diazepine -5-yl)phenyl]-N-(2-hydroxyethyl)-2-nitrobenzenesulfonamide;

[0244] (169) N-[4-(7-chloro-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepine] -1-yl)phenyl]benzenesulfonamide;

[0245] (170) N-[4-(7-bromo-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepine -1-yl)phenyl]benzenesulfonamide;

[0246] (171)N-[4-[(2,4-dioxo-7-(trifluoromethyl)-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepine -1-yl)]phenyl]benzenesulfonamide;

[0247] (172) N-[4-(2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepine -1-yl)phenyl]benzenesulfonamide;

[0248] (173) 1-(2-chlorophenyl)-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-amino)phenyl]methanesulfonamide;

[0249] (174) 1-(3-bromophenyl)-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-amino)phenyl]methanesulfonamide;

[0250] (175) N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho-[1,2-b][1,4]-diazepine -5-yl)phenyl]-2-trifluoromethylbenzenesulfonamide;

[0251] (176) N-[4-(7-bromo-6-methyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepine -1-yl)phenyl]benzenesulfonamide;

[0252] (177) 1-(2-chlorophenyl)-N-[4-(2,4-dioxo-1,2,3,4,8,9,10,11-octahydronaphtho[1,2-b][1,4]diazepine -5-amino)phenyl]methanesulfonamide;

[0253] (178) 3-Bromo-N-[4-(2,4-dioxo-1,2,3,4,8,9,10,11-octahydronaphtho[1,2-b][1,4]diazepine -5-amino)phenyl]benzenesulfonamide;

[0254] (179) N-[4-(2,4-dioxo-1,2,3,4,8,9,10,11-octahydronaphtho[1,2-b][1,4]diazepine -5-amino)phenyl]-3-methoxybenzenesulfonamide;

[0255] (180) 1-(2-bromophenyl)-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-amino)phenyl]methanesulfonamide;

[0256] (181)N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-yl)phenyl]-1-(2-methylphenyl)methanesulfonamide;

[0257] (182) N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-amino)phenyl]-1-(2-nitrophenyl)methanesulfonamide;

[0258] (183)N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-yl)phenyl]-2-phenylethanesulfonamide;

[0259] (184) 1-(2,3-dichlorophenyl)-N-[4-(2,4-dioxo-1,2,3,4,8,9,10,11-octahydronaphtho[1,2-b][1,4]diazepine -5-amino)phenyl]methanesulfonamide;

[0260] (185) 1-(2-chlorophenyl)-N-[4-(2,4-dioxo-7-methoxy-1H-benzo[1,2-b][1,4]diazepine -1-yl)phenyl]methanesulfonamide;

[0261] (186) 1-(2-chlorophenyl)-N-[4-(2,4-dioxo-7-hydroxy-1H-benzo[1,2-b][1,4]diazepine -1-yl)phenyl]methanesulfonamide;

[0262] (187) 1-(4-chlorophenyl)-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-amino)phenyl]methanesulfonamide;

[0263] (188) 1-(2-chlorophenyl)-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-yl)benzyl]methanesulfonamide;

[0264] (189) 1-(2-chlorophenyl)-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-yl)-2-methoxyphenyl]methanesulfonamide;

[0265] (190) 1-(2-chlorophenyl)-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-yl)-2-hydroxyphenyl]methanesulfonamide;

[0266] (191) 1-(2,6-dichlorophenyl)-N-[4-(2,4-dioxo-1,2,3,4,8,9,10,11-octahydronaphtho[1,2-b][1,4]diazepine -5-amino)phenyl]methanesulfonamide;

[0267] (192) 1-(2-chlorophenyl)-N-[4-(2,4-dioxo-6-methyl-1H-benzo[1,2-b][1,4]diazepine -1-yl)phenyl]methanesulfonamide;

[0268] (193) 1-(2-chlorophenyl)-N-[4-(2,4-dioxy-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-amino)propyl]methanesulfonamide;

[0269] (194) 1-(2-chlorophenyl)-N-[2-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-yl)ethyl]methanesulfonamide;

[0270] (195) N-[4-(2,4-dioxo-1,2,3,4,8,9,10,11-octahydronaphtho[1,2-b][1,4]diazepine -5-yl)phenyl]-1-(2-iodophenyl)methanesulfonamide;

[0271] (196) 1-(2-chlorophenyl)-N-[4-(2,4-dioxo-1,2,3,4,8,9,10,11-octahydronaphtho[1,2-b][1,4]diazepine -5-yl)phenyl]-N-methylmethanesulfonamide;

[0272] (197) 1-(2-chlorophenyl)-N-[4-(2-oxo-2,3-dihydro-1H-naphtho[1,2-e][1,4]diazepine -5-amino)phenyl]methanesulfonamide;

[0273] (198) 1-[(2-trifluoromethyl)phenyl]-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-yl)phenyl]phenyl-N-methylmethanesulfonamide;

[0274] (199) 1-(2-ethylphenyl)-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-yl)phenyl]phenyl-N-methylmethanesulfonamide;

[0275] (200) 1-(2,3-dimethylphenyl)-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-yl)phenyl]phenyl-N-methylmethanesulfonamide;

[0276] (201) 2-(2-chlorophenyl)-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-yl)phenyl]phenyl-N-methylethanesulfonamide;

[0277] (202) 1-(2-nitrophenyl)-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-yl)phenyl]phenyl-N-methylmethanesulfonamide;

[0278] (203) 1-(2-aminophenyl)-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-yl)phenyl]phenyl-N-methylmethanesulfonamide;

[0279] (204) 1-(2-dimethylaminophenyl)-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-yl)phenyl]phenyl-N-methylmethanesulfonamide;

[0280] (205) 5-[4-[(pyridin-4-yl)carbonylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-diketone hydrochloride;

[0281] (206) 5-[4-[2-[(pyridin-3-yl)oxy]acetylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-diketone hydrochloride;

[0282] (207) 5-[4-[(pyridin-3-yl)carbonylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-diketone hydrochloride;

[0283] (208) 5-[4-[(2-methylpyridin-3-yl)carbonylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-diketone hydrochloride;

[0284] (209) 5-[4-[(2-chloropyridin-3-yl)carbonylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0285] (210) 5-[4-[2-[(pyridin-2-yl)oxy]acetylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0286] (211) 5-[4-[[4-(trifluoromethyl)pyridin-3-yl]carbonylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0287] (212) 5-[4-[(2-chloropyridin-3-yl)carbonylamino]phenyl]-1H-[1,4]diazepine 2,3-f]isoquinoline-2,4(3H,5H)-dione;

[0288] (213) 5-[4-[(2-chloropyridin-3-yl)carbonylamino]phenyl]-8,9,10,11-tetrahydro-1H-[1,4]diazepine 2,4(3H,5H)-dione; and

[0289] (214) 5-[4-[(2-isopropylbenzoyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione.

[0290] [8] The solid dispersion according to any one of items [1] to [7], wherein the compound or a pharmacologically acceptable salt thereof is amorphous.

[0291] [9] The solid dispersion according to any one of items [1] to [8], wherein the carrier ratio is 1 to 25.

[0292]

[10] The solid dispersion according to any one of items [3] to [9], wherein the SLS ratio is 0.1 to 10.

[0293]

[11] A method for producing a solid dispersion according to any one of items [1] to

[10] , characterized in that the solid dispersion is produced by a spray drying method.

[0294]

[12] A pharmaceutical composition comprising the solid dispersion according to any one of items [1] to

[11] .

[0295]

[13] The pharmaceutical composition according to item

[12] , which is a solid preparation.

[0296] Since the present compound as its active ingredient exhibits high in vivo absorbability, the solid dispersion of the present invention is useful as a therapeutic agent for neuropathic pain, etc. In addition, the pharmaceutical composition of the present invention, which is a solid dispersion, has excellent storage stability. BRIEF DESCRIPTION OF THE DRAWINGS

[0297] Figure 1The dissolution properties of various solid dispersions of compound F48 are shown. (1) Results of dissolution tests of solid dispersions (A to J) of the present compound prepared using 10 types of polymer-containing carriers are shown.

[0298] Figure 2 The dissolution properties of various solid dispersions of compound F48 are shown (2): Results of dissolution tests of various solid dispersions (B1 to B5, E1 to E3) with different carrier ratios and SLS ratios.

[0299] Figure 3 Shown are the results of powder X-ray diffraction of a solid dispersion containing compound F48.

[0300] Figure 4 The analgesic effect of a solid dispersion of compound F48 in the Chung's model is shown. Significant differences were observed compared to the control group (Placevo) (mean ± SE (n = 5-12); #: p < 0.05, ##: p < 0.01, ###: p < 0.001 (30 mg / kg); *: p < 0.05, **: p < 0.01, ***: p < 0.001 (10 mg / kg); $: p < 0.05 (3 mg / kg) (two-way ANOVA / Bonferroni test)).

[0301] Figure 5 Shown are the results of powder X-ray diffraction of a solid dispersion of compound F2 (A) and a solid dispersion of compound F57 (B). DETAILED DESCRIPTION

[0302] Hereinafter, the present invention will be described in detail based on specific embodiments. However, the present invention is not limited to the following embodiments, and can be implemented in any manner without departing from the scope of the present invention.

[0303] It should be noted that all patent publications, patent application publications, non-patent documents, etc. cited in the present disclosure are incorporated herein by reference in their entirety for any purpose.

[0304] In the present disclosure, “to” when applied to numerical values ​​refers to a range of values ​​falling within a range of not less than a predetermined reference value and not more than a predetermined reference value.

[0305] (A) This compound

[0306] In this specification, the present compound is the compound described in Patent Document 1, more specifically, the compound represented by the above-mentioned general formula (I) or general formula (II).

[0307] As the compound of the present invention represented by the general formula (I), the following compounds are preferred.

[0308] (1) A compound represented by the above general formula (I) or a pharmacologically acceptable salt thereof, wherein R 1 and R 2 The groups 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 by 1 to 3 halogen atoms, an alkoxy group having 1 to 8 carbon atoms substituted by 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 number of carbon atoms of the aryl part is 6 to 10 and the number of carbon atoms of the alkylene part is 1 to 8).

[0309] (2) A compound represented by the above general formula (I) or a pharmacologically acceptable salt thereof, wherein R 1 and R 2 Together with the benzene ring to which they are bonded, they form a naphthalene ring or a tetralin ring, and R 1 and R 2 Together and R 1 and R 2 The benzene ring or cyclohexane ring formed by the carbon atoms to which the rings are respectively bonded may be substituted by 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 by 1 to 3 halogen atoms, an alkoxy group having 1 to 8 carbon atoms substituted by 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).

[0310] (3) A compound represented by the above general formula (I) or a pharmacologically acceptable salt thereof, wherein R 1 and R 2 Together with the benzene ring to which they are bonded, they form a naphthalene ring, and R 1 and R 2 Together and R 1 and R 2 The benzene ring formed by the respectively bonded carbon atoms may be substituted by 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 by 1 to 3 halogen atoms, an alkoxy group having 1 to 8 carbon atoms substituted by 1 to 3 halogen atoms, a halogen atom, a hydroxyl group, and an amino group.

[0311] (4) The compound represented by the above general formula (I) or the compound described in (1) to (3) above, or a pharmacologically acceptable salt thereof, wherein R 3 and R 4 The groups 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 by 1 to 3 halogen atoms, an alkoxy group having 1 to 8 carbon atoms substituted by 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 part has 6 to 10 carbon atoms and the alkylene part has 1 to 8 carbon atoms).

[0312] (5) The compound represented by the above general formula (I) or the compound described in (1) to (4) above, or a pharmacologically acceptable salt thereof, wherein R 5 It is a hydrogen atom, an alkyl group having 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).

[0313] (6) The compound represented by the above general formula (I) or the compound described in (1) to (4) above, or a pharmacologically acceptable salt thereof, wherein R 5 A hydrogen atom.

[0314] (7) The compound represented by the above general formula (I) or the compound described in (1) to (6) above, or a pharmacologically acceptable salt thereof, wherein R 6 and R 7 The groups may be the same or different and are 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 by 1 to 3 halogen atoms, or an alkoxy group having 1 to 8 carbon atoms substituted by 1 to 3 halogen atoms.

[0315] (8) The compound represented by the above general formula (I) or the compound described in (1) to (6) above, or a pharmacologically acceptable salt thereof, wherein R 6 and R 7 They are all hydrogen atoms.

[0316] (9) The compound represented by the above general formula (I) or the compound described in (1) to (8) above, or a pharmacologically acceptable salt thereof, wherein X is N, Y is C(=O), and the double line consisting of a solid line and a dotted line is a single bond.

[0317] (10) The compound represented by the above general formula (I) or the compound described in (1) to (8) above, or a pharmacologically acceptable salt thereof, wherein X is C, Y is N, and the double line consisting of a solid line and a dotted line is a double bond.

[0318] (11) The compound represented by the above general formula (I) or the compound described in (1) to (10) above, or a pharmacologically acceptable salt thereof, wherein Z is an oxygen atom.

[0319] (12) A compound represented by the above general formula (I) or a compound described in (1) to (11) above, or a pharmacologically acceptable salt thereof, wherein A is a phenyl or pyridyl group which may have 1 to 4 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 by 1 to 3 halogen atoms, an alkoxy group having 1 to 8 carbon atoms substituted by 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 part has 6 to 10 carbon atoms and the alkylene part has 1 to 8 carbon atoms), a phenyl group or a pyridyl group which may have the same or different substituents as substituents.

[0320] (13) A compound represented by the above general formula (I) or a compound described in (1) to (11) above, or a pharmacologically acceptable salt thereof, wherein A is a phenyl group which may have 1 to 4 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 by 1 to 3 halogen atoms, an alkoxy group having 1 to 8 carbon atoms substituted by 1 to 3 halogen atoms, a halogen atom, a hydroxyl group, a nitro group, a cyano group, or an amino group, which may be the same or different.

[0321] (14) The compound represented by the above general formula (I) or the compound described in (1) to (11) above, or a pharmacologically acceptable salt thereof, wherein A is a bonding site.

[0322] (15) A compound represented by the above general formula (I) or a compound described in (1) to (14) above, or a pharmacologically acceptable salt thereof, wherein B is NHC(=O), NHCONH, CONH, NHC(=S)NH, NHSO2, SO2NH or OSO2.

[0323] (16) The compound represented by the above general formula (I) or the compound described in (1) to (14) above, or a pharmacologically acceptable salt thereof, wherein B is NHC(=O), NHCONH or NHSO2.

[0324] (17) A compound represented by the above general formula (I) or a compound described in (1) to (16) above, or a pharmacologically acceptable salt thereof, wherein D is an alkylene chain having 1 to 6 carbon atoms and having 1 to 4 substituents selected from an alkyl group having 1 to 8 carbon atoms or an alkyl group having 1 to 8 carbon atoms substituted by 1 to 3 halogen atoms, which may be the same or different, as a substituent, and further having a double bond.

[0325] (18) The compound represented by the above general formula (I) or the compound described in (1) to (16) above, or a pharmacologically acceptable salt thereof, wherein D is a bonding site.

[0326] (19) The compound represented by the above-mentioned general formula (I) or the compound described in (1) to (16) above, or a pharmacologically acceptable salt thereof, wherein E is a bonding site.

[0327] (20) A compound represented by the above general formula (I) or a compound described in (1) to (19) above, or a pharmacologically acceptable salt thereof, wherein G is a compound which may have 1 to 4 groups selected from alkyl groups having 1 to 8 carbon atoms, alkenyl groups having 2 to 8 carbon atoms, alkoxy groups having 1 to 8 carbon atoms, alkyl groups having 1 to 8 carbon atoms substituted by 1 to 3 halogen atoms, alkoxy groups having 1 to 8 carbon atoms substituted by 1 to 3 halogen atoms, halogen atoms, hydroxyl groups, nitro groups, or the like. piperazine, piperidine, morpholine, cyclohexane, benzene, naphthalene, quinoline, quinoxaline, benzimidazole, thiophene, imidazole, thiazole, azole, indole, benzofuran, pyrrole, pyridine or pyrimidine.

[0328] (21) A compound represented by the above general formula (I) or a compound described in (1) to (19) above, or a pharmacologically acceptable salt thereof, wherein G is benzene which may have 1 to 4 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 by 1 to 3 halogen atoms, an alkoxy group having 1 to 8 carbon atoms substituted by 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.

[0329] (22) The compound represented by the above-mentioned general formula (I) or the compound described in (1) to (21) above, or a pharmacologically acceptable salt thereof, wherein m is 0.

[0330] As the compound of the present invention represented by the general formula (II), the following compounds are preferred.

[0331] (23) A compound represented by the above-mentioned general formula (II) or a pharmacologically acceptable salt thereof, wherein:

[0332]

[0333] It is a naphthalene ring or a tetrahydronaphthalene ring which may be substituted by 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 by 1 to 3 halogen atoms, an alkoxy group having 1 to 8 carbon atoms substituted by 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).

[0334] (24) A compound represented by the above-mentioned general formula (II) or a pharmacologically acceptable salt thereof, wherein:

[0335]

[0336] It is a naphthalene ring which 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, and an amino group.

[0337] (25) The compound represented by the above general formula (II) or the compound described in (23) or (24) above, or a pharmacologically acceptable salt thereof, wherein R 3a and R 4a The groups 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 by 1 to 3 halogen atoms, an alkoxy group having 1 to 8 carbon atoms substituted by 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 part has 6 to 10 carbon atoms and the alkylene part has 1 to 8 carbon atoms).

[0338] (26) The compound represented by the above general formula (II) or the compound described in (23) to (25) above, or a pharmacologically acceptable salt thereof, wherein R 5a It is a hydrogen atom, an alkyl group having 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).

[0339] (27) The compound represented by the above general formula (II) or the compound described in (23) to (25) above, or a pharmacologically acceptable salt thereof, wherein R 5a A hydrogen atom.

[0340] (28) The compound represented by the above general formula (II) or the compound described in (23) to (27) above, or a pharmacologically acceptable salt thereof, wherein R 6a and R 7a The groups may be the same or different and are 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 by 1 to 3 halogen atoms, or an alkoxy group having 1 to 8 carbon atoms substituted by 1 to 3 halogen atoms.

[0341] (29) The compound represented by the above general formula (II) or the compound described in (23) to (27) above, or a pharmacologically acceptable salt thereof, wherein R 6a and R 7a They are all hydrogen atoms.

[0342] (30) The compound represented by the above general formula (II) or the compound described in (23) to (29) above or a pharmacologically acceptable salt thereof, wherein:

[0343]

[0344] It is a phenyl or pyridyl group which may have 1 to 4 substituents which may be the same or different and 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 by 1 to 3 halogen atoms, an alkoxy group having 1 to 8 carbon atoms substituted by 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 part has 6 to 10 carbon atoms and the alkylene part has 1 to 8 carbon atoms), a phenyl group or a pyridyl group.

[0345] (31) The compound represented by the above general formula (II) or the compound described in (23) to (29) above or a pharmacologically acceptable salt thereof, wherein:

[0346]

[0347] It is a phenyl 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 by 1 to 3 halogen atoms, an alkoxy group having 1 to 8 carbon atoms substituted by 1 to 3 halogen atoms, a halogen atom, a hydroxyl group, a nitro group, a cyano group, or an amino group as a substituent.

[0348] (32) The compound represented by the above general formula (II) or the compound described in (23) to (29) above or a pharmacologically acceptable salt thereof, wherein:

[0349]

[0350] is the bonding site.

[0351] (33) The compound represented by the above general formula (II) or the compound described in (23) to (32) above or a pharmacologically acceptable salt thereof, wherein B a is NHC(=O), NHCONH, CONH, NHC(=S)NH, NHSO2, SO2NH or OSO2.

[0352] (34) The compound represented by the above general formula (II) or the compound described in (23) to (32) above or a pharmacologically acceptable salt thereof, wherein B a is NHC(=O), NHCONH or NHSO2.

[0353] (35) The compound represented by the above general formula (II) or the compound described in (23) to (34) above or a pharmacologically acceptable salt thereof, wherein E a is the bonding site.

[0354] (36) The compound represented by the above general formula (II) or the compound described in (23) to (35) above or a pharmacologically acceptable salt thereof, wherein G a piperazine, piperidine, morpholine, cyclohexane, benzene, naphthalene, quinoline, quinoxaline, benzimidazole, thiophene, imidazole, thiazole, which may have 1 to 4 substituents selected from the group consisting of 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, which may have 1 to 4 substituents selected from the group consisting of azole, indole, benzofuran, pyrrole, pyridine or pyrimidine.

[0355] (37) The compound represented by the above general formula (II) or the compound described in (23) to (35) above or a pharmacologically acceptable salt thereof, wherein G a Benzene which may have 1 to 4 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 by 1 to 3 halogen atoms, an alkoxy group having 1 to 8 carbon atoms substituted by 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.

[0356] (38) The compound represented by the above general formula (II) or the compound described in (23) to (37) above, or a pharmacologically acceptable salt thereof, wherein n is 0.

[0357] As the compound of the present invention represented by the general formula (II), the compounds shown in the following table are more preferred.

[0358] Among the compounds of the general formula (II) used in the solid dispersion of the present invention, preferred compounds include the compounds listed in Table 1.

[0359] [Table 1]

[0360] <![CDATA[B a (Replacement position)]]> n <![CDATA[E a ]]> <![CDATA[G a ]]> Compound number NHCo(4) 0 bonding site Phenyl F1 NHCo(4) 0 bonding site <![CDATA[(2-CF3)phenyl]]> F2 NHCO(4) 0 bonding site (2-I)phenyl F48 NHCO(4) 0 bonding site (2-F)phenyl F97 NHCO(4) 0 bonding site (2-Br)phenyl F47 NHCO(4) 0 bonding site (2-Cl)phenyl F46 NHCO(4) 0 bonding site (2,3-Me)phenyl F14 NHCO(4) 0 bonding site (2-Et)phenyl F57 NHCO(4) 0 bonding site (2-iPr)phenyl F214 NHCO(4) 0 bonding site (2-tBu)phenyl F71 NHCO(4) 0 bonding site (6-C1,2-OH)phenyl F118 NHCO(4) 0 bonding site (2-C1,3-OH)phenyl F32 <![CDATA[NHSO2(4)]]> 0 bonding site Phenyl F146 <![CDATA[NHSO2(4)]]> 0 bonding site (3-Br)phenyl F147 <![CDATA[NHSO2(4)]]> 1 bonding site Phenyl F160 <![CDATA[NHSO2(4)]]> 1 bonding site (2-C1)phenyl F173 <![CDATA[NHSO2(4)]]> 1 bonding site (2-Br)phenyl F180

[0361] As the compound of the present invention represented by the above-mentioned general formula (I) or (II), the following compounds are particularly preferred.

[0362] (Compound F1) 5-(4-Benzoylaminophenyl)-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione;

[0363] (Compound F2) 5-[4-[2-(trifluoromethyl)benzoyl]aminophenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione;

[0364] (Compound F3) 5-[4-(3-bromobenzoyl)aminophenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione;

[0365] (Compound F4) 5-[4-[4-(trifluoromethyl)benzoyl]aminophenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione;

[0366] (Compound F5) 5-[4-(2-Methylbenzoyl)aminophenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione;

[0367] (Compound F6) 5-[4-(2,6-Dimethylbenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione;

[0368] (Compound F7) 5-[4-(2,6-Dichlorobenzoyl)aminophenyl]-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione;

[0369] (Compound F8) 5-[4-(3-chlorobenzoyl)aminophenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0370] (Compound F9) 5-[4-(2-phenylacetylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0371] (Compound F10) 1-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-amino)phenyl]-3-phenylthiourea;

[0372] (Compound F11) 5-[4-(2,3-dimethoxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0373] (Compound F12) 5-[4-(2-methoxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0374] (Compound F13) 5-[4-[(2-chlorophenylacetyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0375] (Compound F14) 5-[4-(2,3-dimethylbenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0376] (Compound F15) 5-[4-(2,5-dimethylbenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0377] (Compound F16) 5-[4-(5-bromo-2-chlorobenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0378] (Compound F17) 5-[4-(2,4-dichlorobenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0379] (Compound F18) 5-[4-(2-hydroxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0380] (Compound F19) 5-[4-(2,3-dihydroxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0381] (Compound F20) 1-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-amino)phenyl]-3-phenylurea;

[0382] (Compound F21) 5-[4-[(2,6-dichlorophenylacetyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0383] (Compound F22) 5-[4-[(2-methoxyphenylacetyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0384] (Compound F23) 5-[4-[(2-hydroxyphenylacetyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0385] (Compound F24) 1-(2-chlorophenyl)-3-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-amino)phenyl]thiourea;

[0386] (Compound F25) 5-[4-[3-(trifluoromethyl)benzoylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0387] (Compound F26) 5-[4-[2-[2-(trifluoromethyl)phenyl]acetylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0388] (Compound F27) 1-(2-chlorophenyl)-3-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-amino)phenyl]urea;

[0389] (Compound F28) 5-[4-[(2-phenylpropionyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0390] (Compound F29) 5-[4-(2-chloro-3-methoxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0391] (Compound F30) 5-[4-(3-phenylpropionylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0392] (Compound F31) 5-[4-[(1H-indole-3-carbonyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0393] (Compound F32) 5-[4-(2-chloro-3-hydroxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0394] (Compound F33) 5-[4-[(2-methyl-2-phenylpropionyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0395] (Compound F34) 5-[4-(2-phenoxyacetylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0396] (Compound F35) 5-[4-[2-(2-chloro-4-methoxyphenyl)acetylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0397] (Compound F36) 5-[4-[(1-methyl-1H-imidazole-2-carbonyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0398] (Compound F37) 5-[4-[2-(2,4-dichlorophenyl)acetylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0399] (Compound F38) 5-[4-[2-(2-chloro-4-hydroxyphenyl)acetylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0400] (Compound F39) 5-[4-(3-phenylpropenylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0401] (Compound F40) 5-[4-[(3-pyridylacetyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-diketone hydrochloride;

[0402] (Compound F41) 5-[4-(1H-benzimidazole-2-carbonylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0403] (Compound F42) 1-[4-(2,3-dimethylbenzoylamino)phenyl]-7-methoxy-1H-1,5-benzodiazepine -2,4(3H,5H)-dione;

[0404] (Compound F43) 5-[4-[(Benzoylamino)methyl]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0405] (Compound F44) 5-[4-[(2-chlorobenzoylamino)methyl]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0406] (Compound F45) 1-[4-(2,3-dimethylbenzoylamino)phenyl]-7-hydroxy-1H-1,5-benzodiazepine -2,4(3H,5H)-dione;

[0407] (Compound F46) 5-[4-(2-chlorobenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0408] (Compound F47) 5-[4-(2-bromobenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0409] (Compound F48) 5-[4-(2-iodobenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0410] (Compound F49) 5-[4-(2,3-dimethylbenzoylamino)-3-fluorophenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0411] (Compound F50) 5-[4-[2-(2-methylphenyl)acetylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0412] (Compound F51) 5-[4-[(Quinoxalin-2-yl)carbonylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0413] (Compound F52) 5-[4-[(5-methylthiophen-2-yl)carbonylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0414] (Compound F53) 5-[3-[(2-chlorophenylacetyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0415] (Compound F54) 5-[4-[(2,4,6-trimethylbenzoyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0416] (Compound F55) 5-[4-(cyclohexylcarbonylamino)phenyl]-1,2,3,4,8,9,10,11-octahydronaphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0417] (Compound F56) 1-[4-(2,3-dimethylbenzoyl)aminophenyl]-6-methyl-1H-1,5-benzodiazepine -2,4(3H,5H)-dione;

[0418] (Compound F57) 5-[4-[(2-ethylbenzoyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0419] (Compound F58) 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;

[0420] (Compound F59) 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;

[0421] (Compound F60) 1-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-amino)phenyl]-3-(2-methylphenyl)thiourea;

[0422] (Compound F61) 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;

[0423] (Compound F62) 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;

[0424] (Compound F63) 5-[4-(2,3-dimethylbenzoylamino)-3-hydroxyphenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0425] (Compound F64) 5-[4-(2-chloro-3-methoxybenzoylamino)phenyl]-1,3-dihydronaphtho[1,2-e]-1,4-diazepine -2-ketone;

[0426] (Compound F65) 5-[4-[(4-dimethylaminobenzoyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0427] (Compound F66) 5-[4-[2-(2,4-dichlorophenoxy)acetylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0428] (Compound F67) 5-[4-[2-(2-methylphenoxy)acetylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0429] (Compound F68) N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-yl)butyl]-2-chloro-3-methoxybenzamide;

[0430] (Compound F69) 5-[4-(2-chloro-3-hydroxybenzoylamino)phenyl]-1,3-dihydronaphtho[1,2-e]-1,4-diazepine -2-ketone;

[0431] (Compound F70) 5-[4-(2-acetylbenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0432] (Compound F71) 5-[4-(2-tert-Butylbenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0433] (Compound F72) 5-[2-(2-iodobenzoyl)aminoethyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0434] (Compound F73) 5-[3-[(2-iodobenzoyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0435] (Compound F74) 6,7-dimethyl-1-[4-(2-iodobenzoyl)aminophenyl]-1H-1,5-benzodiazepine -2,4(3H,5H)-dione;

[0436] (Compound F75) 5-[4-[(1-methylpiperidin-4-yl)carbonylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-diketone hydrochloride;

[0437] (Compound F76) 5-[4-[(Benzofuran-2-yl)carbonylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0438] (Compound F77) 5-[4-[(1-methyl-1H-indol-3-yl)carbonylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0439] (Compound F78) 5-[4-(2-propenylbenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0440] (Compound F79) 5-[4-(2-propylbenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0441] (Compound F80) 5-[3-Fluoro-4-(2-iodobenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0442] (Compound F81) 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;

[0443] (Compound F82) 5-[4-[(2-isopropoxybenzoyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0444] (Compound F83) 5-[4-[(3-methylthiophen-2-yl)carbonylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0445] (Compound F84) 5-[4-(2-phenoxypropionylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0446] (Compound F85) 5-[4-[2-(4-chloro-2-methylphenoxy)acetylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0447] (Compound F86) 5-[4-[(4-fluoro-2-trifluoromethyl)benzoyl]aminophenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0448] (Compound F87) 5-[4-(4-Fluoro-2-methoxybenzoyl)aminophenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0449] (Compound F88) 5-[4-(4-Fluoro-2-hydroxybenzoyl)aminophenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0450] (Compound F89) 5-[3-[(2-iodophenylacetyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0451] (Compound F90) 5-[4-(2-methyl-2-phenoxypropionylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0452] (Compound F91) 5-[4-(2-tert-Butylbenzoylamino)phenyl]-1,3-dihydronaphtho[1,2-e]-1,4-diazepine -2-ketone;

[0453] (Compound F92) 5-[4-[(3-dimethylaminobenzoyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0454] (Compound F93) 5-[4-(4-iodo-2-methoxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0455] (Compound F94) 5-[4-(6-Fluoro-2-methoxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0456] (Compound F95) 5-[4-(2-hydroxy-4-iodobenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0457] (Compound F96) 5-[4-(6-Fluoro-2-hydroxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0458] (Compound F97) 5-[4-(2-Fluorobenzoyl)aminophenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0459] (Compound F98) 5-[4-[(2-dimethylaminobenzoyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0460] (Compound F99) 5-[4-(2-methoxy-6-methylbenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0461] (Compound F100) 5-[4-(2-Hydroxy-6-methylbenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0462] (Compound F101) 5-[4-[3-(2-methylphenyl)propionylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0463] (Compound F102) 5-(4-phenylcarbamoylphenyl)-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0464] (Compound F103) 5-(4-Benzylcarbamoylphenyl)-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0465] (Compound F104) 5-[4-[3-(2-methylphenyl)acryloylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0466] (Compound F105) 5-[4-[3-(2-chlorophenyl)propionylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0467] (Compound F106) 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;

[0468] (Compound F107) 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;

[0469] (Compound F108) 5-[4-(2-chlorobenzyl)carbamoylphenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0470] (Compound F109) 5-[4-[3-(2-chlorophenyl)acryloylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0471] (Compound F110) 5-[4-(2-chlorophenyl)carbamoylphenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0472] (Compound F111) 5-[4-(6-bromo-2,3-methylenedioxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0473] (Compound F112) 5-[4-(6-bromo-2-methoxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0474] (Compound F113) 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;

[0475] (Compound F114) 5-[2-(2-iodobenzoyl)aminopyridin-5-yl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0476] (Compound F115) 5-[4-(6-bromo-2-hydroxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0477] (Compound F116) 5-[4-(6-chloro-2-methoxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0478] (Compound F117) 5-[4-(2-iodobenzoylamino)phenyl]-1H-[1,4]diazepine 2,3-h]quinoline-2,4(3H,5H)-dione;

[0479] (Compound F118) 5-[4-(6-chloro-2-hydroxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0480] (Compound F119) 5-[4-(2-Hydroxy-6-methoxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0481] (Compound F120) 5-[4-[2-methoxy-6-(trifluoromethyl)benzoylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0482] (Compound F121) 5-[4-[2-Hydroxy-6-(trifluoromethyl)benzoylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0483] (Compound F122) 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;

[0484] (Compound F123) 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;

[0485] (Compound F124) 5-[4-[2-chloro-5-(methylthio)benzoylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0486] (Compound F125) 5-[4-[2-(methylthio)benzoylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0487] (Compound F126) 5-[4-[3-(methylthio)benzoylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0488] (Compound F127) 5-[4-[2-ethyl-6-methoxybenzoylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0489] (Compound F128) 5-[4-(3-methylsulfonylbenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0490] (Compound F129) 6-ethyl-1-[4-(2-iodobenzoyl)aminophenyl]-1H-1,5-benzodiazepine -2,4(3H,5H)-dione;

[0491] (Compound F130) 5-[4-[2-ethyl-6-hydroxybenzoylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0492] (Compound F131) 5-[4-(3-methanesulfinylbenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0493] (Compound F132) 5-[4-(2-chloro-5-methanesulfinylbenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0494] (Compound F133) 5-[4-(2-methanesulfinylbenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0495] (Compound F134) 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)-diketone hydrochloride;

[0496] (Compound F135) 5-[4-(2-chloro-6-methoxybenzoylamino)phenyl]-1,3-dihydronaphtho[1,2-e]-1,4-diazepine -2-ketone;

[0497] (Compound F136) 5-[4-[[(3-chloropyridin-2-yl)carbonyl]amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0498] (Compound F137) 5-[4-(2-chloro-6-hydroxybenzoylamino)phenyl]-1,3-dihydronaphtho[1,2-e]-1,4-diazepine -2-ketone;

[0499] (Compound F138) 5-[4-(3-chloro-2-methoxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0500] (Compound F139) 5-[4-[(3-methylpyridin-2-yl)carbonylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0501] (Compound F140) 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;

[0502] (Compound F141) 5-[4-(3-chloro-2-hydroxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0503] (Compound F142) 5-[4-[[(3-Hydroxypyridin-2-yl)carbonyl]amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0504] (Compound F143) 5-[4-[(3-vinylpyridin-2-yl)carbonylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0505] (Compound F144) 5-[4-[(3-ethylpyridin-2-yl)carbonylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0506] (Compound F145) N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho-[1,2-b][1,4]-diazepine -5-amino)phenyl]-2-nitrobenzenesulfonamide;

[0507] (Compound F146) N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine] -5-amino)phenyl]benzenesulfonamide;

[0508] (Compound F147) 3-Bromo-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-amino)phenyl]benzenesulfonamide;

[0509] (Compound F148) N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-amino)phenyl]-3-methoxybenzenesulfonamide;

[0510] (Compound F149) N-[3-(2-oxo-2,3-dihydro-1H-naphtho[1,2-e][1,4]diazepine] -5-amino)phenyl]benzenesulfonamide;

[0511] (Compound F150) N-[3-(2,4-dioxo-1,2,3,4-tetrahydronaphtho-[1,2-b][1,4]-diazepine -5-amino)phenyl]-2-nitrobenzenesulfonamide;

[0512] (Compound F151) N-[4-(2,4-dioxo-1,2,3,4,8,9,10,11-octahydro-naphtho[1,2-b][1,4]-diazepine] -5-amino)phenyl]-2-nitro-benzenesulfonamide;

[0513] (Compound F152) N-[4-(2,4-dioxo-1,2,3,4,8,9,10,11-octahydro-naphtho[1,2-b][1,4]-diazepine -5-amino)phenyl]-N-methyl-2-nitrobenzenesulfonamide;

[0514] (Compound F153) N-[3-(2,4-dioxo-1,2,3,4-tetrahydronaphtho-[1,2-b][1,4]-diazepine -5-amino)phenyl]-N-methyl-2-nitrobenzenesulfonamide;

[0515] (Compound F154) 4-(2,4-dioxo-1,2,3,4,8,9,10,11-octahydronaphtho[1,2-b][1,4]diazepine -5-yl)-N-phenylbenzenesulfonamide;

[0516] (Compound F155) N-[3-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b]-[1,4]diazepine -5-yl)phenyl]-2-naphthalenesulfonamide;

[0517] (Compound F156) N-[3-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b]-[1,4]diazepine -5-yl)phenyl]-1-naphthalenesulfonamide;

[0518] (Compound F157) N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-amino)phenyl]cyclohexanesulfonamide;

[0519] (Compound F158) N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-amino)phenyl]-3-pyridinesulfonamide hydrochloride;

[0520] (Compound F159) N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-amino)phenyl]-4-isopropylbenzenesulfonamide;

[0521] (Compound F160) N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-amino)phenyl]phenylmethanesulfonamide;

[0522] (Compound F161) N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-yl)phenyl]-3-pyridinesulfonamide;

[0523] (Compound F162) N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-yl)phenyl]-2-naphthalenesulfonamide;

[0524] (Compound F163) 4-(2,4-dioxo-1,2,3,4,8,9,10,11-octahydronaphtho-[1,2-b][1,4]diazepine -5-yl)phenyl 3-bromobenzenesulfonate;

[0525] (Compound F164) N-benzyl-N-[4-(1-benzyl-2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-amino)phenyl]-2-nitrobenzenesulfonamide;

[0526] (Compound F165) N-benzyl-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-amino)phenyl]-2-nitrobenzenesulfonamide;

[0527] (Compound F166) 3-Bromo-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-yl)phenyl]-N-methylbenzenesulfonamide;

[0528] (Compound F167) N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho-[1,2-b][1,4]-diazepine -5-amino)phenyl]-N-methyl-2-nitrobenzenesulfonamide;

[0529] (Compound F168) N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho-[1,2-b][1,4]-diazepine -5-yl)phenyl]-N-(2-hydroxyethyl)-2-nitrobenzenesulfonamide;

[0530] (Compound F169) N-[4-(7-chloro-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepine] -1-yl)phenyl]benzenesulfonamide;

[0531] (Compound F170) N-[4-(7-bromo-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepine] -1-yl)phenyl]benzenesulfonamide;

[0532] (Compound F171) N-[4-[(2,4-dioxo-7-(trifluoromethyl)-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepine -1-yl)]phenyl]benzenesulfonamide;

[0533] (Compound F172) N-[4-(2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepine] -1-yl)phenyl]benzenesulfonamide;

[0534] (Compound F173) 1-(2-chlorophenyl)-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-amino)phenyl]methanesulfonamide;

[0535] (Compound F174) 1-(3-Bromophenyl)-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-amino)phenyl]methanesulfonamide;

[0536] (Compound F175) N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho-[1,2-b][1,4]-diazepine -5-yl)phenyl]-2-trifluoromethylbenzenesulfonamide;

[0537] (Compound F176) N-[4-(7-bromo-6-methyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepine] -1-yl)phenyl]benzenesulfonamide;

[0538] (Compound F177) 1-(2-chlorophenyl)-N-[4-(2,4-dioxo-1,2,3,4,8,9,10,11-octahydronaphtho[1,2-b][1,4]diazepine -5-amino)phenyl]methanesulfonamide;

[0539] (Compound F178) 3-Bromo-N-[4-(2,4-dioxo-1,2,3,4,8,9,10,11-octahydronaphtho[1,2-b][1,4]diazepine -5-amino)phenyl]benzenesulfonamide;

[0540] (Compound F179) N-[4-(2,4-dioxo-1,2,3,4,8,9,10,11-octahydronaphtho[1,2-b][1,4]diazepine] -5-amino)phenyl]-3-methoxybenzenesulfonamide;

[0541] (Compound F180) 1-(2-bromophenyl)-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-amino)phenyl]methanesulfonamide;

[0542] (Compound F181) N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-yl)phenyl]-1-(2-methylphenyl)methanesulfonamide;

[0543] (Compound F182) N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-amino)phenyl]-1-(2-nitrophenyl)methanesulfonamide;

[0544] (Compound F183) N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-yl)phenyl]-2-phenylethanesulfonamide;

[0545] (Compound F184) 1-(2,3-dichlorophenyl)-N-[4-(2,4-dioxo-1,2,3,4,8,9,10,11-octahydronaphtho[1,2-b][1,4]diazepine -5-amino)phenyl]methanesulfonamide;

[0546] (Compound F185) 1-(2-chlorophenyl)-N-[4-(2,4-dioxo-7-methoxy-1H-benzo[1,2-b][1,4]diazepine -1-yl)phenyl]methanesulfonamide;

[0547] (Compound F186) 1-(2-chlorophenyl)-N-[4-(2,4-dioxo-7-hydroxy-1H-benzo[1,2-b][1,4]diazepine -1-yl)phenyl]methanesulfonamide;

[0548] (Compound F187) 1-(4-chlorophenyl)-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-amino)phenyl]methanesulfonamide;

[0549] (Compound F188) 1-(2-chlorophenyl)-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-yl)benzyl]methanesulfonamide;

[0550] (Compound F189) 1-(2-chlorophenyl)-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-yl)-2-methoxyphenyl]methanesulfonamide;

[0551] (Compound F190) 1-(2-chlorophenyl)-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-yl)-2-hydroxyphenyl]methanesulfonamide;

[0552] (Compound F191) 1-(2,6-dichlorophenyl)-N-[4-(2,4-dioxo-1,2,3,4,8,9,10,11-octahydronaphtho[1,2-b][1,4]diazepine -5-amino)phenyl]methanesulfonamide;

[0553] (Compound F192) 1-(2-chlorophenyl)-N-[4-(2,4-dioxo-6-methyl-1H-benzo[1,2-b][1,4]diazepine -1-yl)phenyl]methanesulfonamide;

[0554] (Compound F193) 1-(2-chlorophenyl)-N-[4-(2,4-dioxy-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-amino)propyl]methanesulfonamide;

[0555] (Compound F194) 1-(2-chlorophenyl)-N-[2-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-yl)ethyl]methanesulfonamide;

[0556] (Compound F195) N-[4-(2,4-dioxo-1,2,3,4,8,9,10,11-octahydronaphtho[1,2-b][1,4]diazepine] -5-yl)phenyl]-1-(2-iodophenyl)methanesulfonamide;

[0557] (Compound F196) 1-(2-chlorophenyl)-N-[4-(2,4-dioxo-1,2,3,4,8,9,10,11-octahydronaphtho[1,2-b][1,4]diazepine -5-yl)phenyl]-N-methylmethanesulfonamide;

[0558] (Compound F197) 1-(2-chlorophenyl)-N-[4-(2-oxo-2,3-dihydro-1H-naphtho[1,2-e][1,4]diazepine -5-amino)phenyl]methanesulfonamide;

[0559] (Compound F198) 1-[2-(Trifluoromethyl)phenyl]-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-yl)phenyl]phenyl-N-methylmethanesulfonamide;

[0560] (Compound F199) 1-(2-ethylphenyl)-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-yl)phenyl]phenyl-N-methylmethanesulfonamide;

[0561] (Compound F200) 1-(2,3-dimethylphenyl)-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-yl)phenyl]phenyl-N-methylmethanesulfonamide;

[0562] (Compound F201) 2-(2-chlorophenyl)-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-yl)phenyl]phenyl-N-methylethanesulfonamide;

[0563] (Compound F202) 1-(2-nitrophenyl)-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-yl)phenyl]phenyl-N-methylmethanesulfonamide;

[0564] (Compound F203) 1-(2-aminophenyl)-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-yl)phenyl]phenyl-N-methylmethanesulfonamide;

[0565] (Compound F204) 1-(2-dimethylaminophenyl)-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-yl)phenyl]phenyl-N-methylmethanesulfonamide;

[0566] (Compound F205) 5-[4-[(pyridin-4-yl)carbonylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-diketone hydrochloride;

[0567] (Compound F206) 5-[4-[2-[(pyridin-3-yl)oxy]acetylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-diketone hydrochloride;

[0568] (Compound F207) 5-[4-[(pyridin-3-yl)carbonylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-diketone hydrochloride;

[0569] (Compound F208) 5-[4-[(2-methylpyridin-3-yl)carbonylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-diketone hydrochloride;

[0570] (Compound F209) 5-[4-[(2-chloropyridin-3-yl)carbonylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0571] (Compound F210) 5-[4-[2-[(pyridin-2-yl)oxy]acetylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0572] (Compound F211) 5-[4-[[4-(Trifluoromethyl)pyridin-3-yl]carbonylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione;

[0573] (Compound F212) 5-[4-[(2-chloropyridin-3-yl)carbonylamino]phenyl]-1H-[1,4]diazepine 2,3-f]isoquinoline-2,4(3H,5H)-dione;

[0574] (Compound F213) 5-[4-[(2-chloropyridin-3-yl)carbonylamino]phenyl]-8,9,10,11-tetrahydro-1H-[1,4]diazepine 2,4(3H,5H)-dione; and

[0575] (Compound F214) 5-[4-[(2-Isopropylbenzoyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione.

[0576] Examples of the pharmacologically acceptable salts of the compounds represented by the above general formula (I) or (II) include hydrochlorides and alkali metal salts such as sodium, potassium and lithium.

[0577] Furthermore, the compounds of the present invention may exist in optical isomers such as cis-trans isomers, optically active forms, and racemic forms, all of which are encompassed by the present invention.

[0578] The compound represented by the above-mentioned general formula (I) or (II) or a pharmacologically acceptable salt thereof can be produced by a known method, for example, the method described in Patent Document 1.

[0579] (B) Solid dispersion

[0580] In this specification, a solid dispersion refers to a dispersion of an active pharmaceutical ingredient in an inactive matrix (also referred to as a "carrier") in which the active pharmaceutical ingredient may be present in a microcrystalline or amorphous state. The matrix in the solid dispersion typically comprises a polymer. In this specification, the active pharmaceutical ingredient is a P2X4 receptor antagonist, specifically a compound represented by the above-mentioned general formula (I) or (II) or a salt thereof.

[0581] Examples of polymers that can be used in the solid dispersion include cellulose derivatives such as hydroxypropylcellulose and hydroxypropylmethylcellulose (HPMC), cellulose ethers (e.g., cellulose alkyl ethers such as ethylcellulose, ethylmethylcellulose, ethylpropylcellulose, isopropylcellulose, and butylcellulose, cellulose aralkyl ethers such as benzylcellulose, and cellulose cyanoalkyl ethers such as cyanoethylcellulose), cellulose esters (e.g., cellulose fatty acid esters such as cellulose acetate, cellulose propionate, and hydroxymethylcellulose acetate succinate, cellulose aromatic carboxylic acid esters such as cellulose acetate phthalate, hydroxypropylmethylcellulose phthalate, and hydroxypropylmethylcellulose acetate succinate (HPMCAS), and polysaccharides such as hyaluronic acid and pullulan. Among these polysaccharides, HPMCAS and HPMC are preferably used, and HPMC is particularly preferably used. As HPMC, commercially available products can be used. Examples thereof include TC-5R, TC-5E, TC-5M, and Pharmacoat P-606 manufactured by Shin-Etsu Chemical Co., Ltd., and METHOCEL E3 and E5 manufactured by Dupont.

[0582] Examples of polymers that can be used in the solid dispersion include (meth)acrylic acid polymers: (meth)acrylic acid monomers ((meth)acrylic acid or its salts (e.g., ammonium salts, amine salts, alkali metal salts, etc.); (meth)acrylic acid C1-10 alkyl ester monomers such as methyl (meth)acrylate and ethyl (meth)acrylate; (meth)acrylic acid di-C1-4 alkylamino C2-4 alkyl esters such as N,N-dimethylaminoethyl (meth)acrylate or their salts (e.g., quaternary ammonium salts, hydrochlorides, etc.); and copolymers of (meth)acrylic acid monomers and copolymerizable monomers (e.g., styrene monomers, vinyl ester monomers, heterocyclic vinyl monomers, and vinyl monomers such as polymerizable unsaturated dicarboxylic acids or their derivatives). Specific examples include "Eudragit RSPO" (ammonium alkyl methacrylate copolymer), "Eudragit NE30D" (ethyl acrylate / methyl methacrylate copolymer dispersion), and "Eudragit" (ethyl methacrylate / methyl methacrylate copolymer dispersion) manufactured by Rohm Pharma. Trade name "Eudragit RS30D" (ammonium alkyl methacrylate copolymer dispersion), trade name "Eudragit RL30D" (ammonium alkyl methacrylate copolymer dispersion), trade name "Eudragit EPO" (aminoalkyl methacrylate copolymer E), trade name "Eudragit L100-55" (dried methacrylic acid copolymer LD), trade name "Eudragit S-100" (methacrylic acid copolymer S), trade name "Eudragit E100" (aminoalkyl methacrylate copolymer E), etc. Among these, "Eudragit L100-55" and "Eudragit E100" can be preferably used, and "Eudragit E100" can be particularly preferably used.

[0583] Examples of polymers that can be used in solid dispersions include water-soluble synthetic polymers such as polyvinyl pyrrolidone (PVP K90, etc.), polyvinyl alcohol, copovidone, polyvinyl acetate phthalate, polyvinyl acetal diethylaminoacetate, polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (product name: SolPlus), polyvinyl pyrrolidone-vinyl acetate resin (Kollidon (registered trademark) SR, etc.), carboxyvinyl polymers, polyethylene glycol (e.g., PEG6000), and polyoxyethylene / polyoxypropylene block copolymers (e.g., Poloxamer P188).

[0584] The "solid dispersion" of the present invention may contain, in addition to the compound represented by the above-mentioned general formula (I) or (II) or its pharmaceutically acceptable salt, and the above-mentioned polymer, a pharmaceutically acceptable additive as a carrier as needed. As pharmaceutically acceptable additives contained as needed, for example, additives selected from surfactants, pH regulators, sugars and plasticizers can be exemplified. These can be appropriately combined and mixed in the solid dispersion of the present invention in the required amount. In the "solid dispersion" of the present invention, the above-mentioned pharmaceutically acceptable additives can constitute the dispersed phase of the solid dispersion, and can also constitute the continuous phase.

[0585] Examples of surfactants that can be used include sodium bis-(2-ethylhexyl)sulfosuccinate (docusate sodium), cationic surfactants such as alkyltrimethylammonium bromide (e.g., hexadecyltrimethylammonium bromide (cetrimonium bromide)), anionic surfactants such as sodium lauryl sulfate (SLS), polyoxyethylene sorbitan (e.g., Tween TM 20, 40, 60, 80 or 85)), sorbitan fatty acid esters (e.g., Span TM 20, 40, 60, 80 or 85)) such nonionic surfactant. Among these, SLS can be preferably used.

[0586] Examples of usable pH adjusters include acids such as succinic acid, maleic acid, tartaric acid, citric acid, and aspartic acid; and bases such as sodium hydroxide, magnesium oxide, silicon dioxide, sodium hydrogen carbonate, and L-arginine.

[0587] Examples of usable sugars include lactose, sucrose, glucose, fructose, sucrose, maltose, reduced maltose, maltitol, mannitol, erythritol, sorbitol, and xylitol.

[0588] Examples of the plasticizer that can be used include triethyl citrate and triacetin.

[0589] The "solid dispersion" of the present invention contains, as an active pharmaceutical ingredient, a compound represented by the above-mentioned general formula (I) or (II) or a pharmaceutically acceptable salt thereof, and a carrier composed of the above-mentioned polymer and the above-mentioned additives. The weight ratio of the carrier to the active pharmaceutical ingredient (referred to herein as the "carrier ratio") is in the range of 0.5-100, 1-50, 1-25, 1-20, 1-15, 1-10, 1-8, 1-5, 2-50, 2-25, 2-20, 2-15, 2-10, 2-8, 2-5, 3-50, 3-25, 3-20, 3-15, 3-10, 3-8, or 3-5, more preferably 1-25, 1-20, 1-15, 1-10, or 1-5. The carrier ratio of the "solid dispersion" of the present invention is preferably as low as possible, taking into account the size, wettability, and production cost, as long as dissolution, absorption, and stability are sufficient.

[0590] One embodiment of the "solid dispersion" of the present invention comprises, as an active pharmaceutical ingredient, a compound represented by the above-mentioned general formula (I) or (II) or a pharmaceutically acceptable salt thereof, and Eudragit E100, wherein the carrier ratio is in the range of 0.5-100, 1-50, 1-25, 1-20, 1-15, 1-10, 1-8, 1-5, 2-50, 2-25, 2-20, 2-15, 2-10, 2-8, 2-5, 3-50, 3-25, 3-20, 3-15, 3-10, 3-8, or 3-5, more preferably 1-25, 1-20, 1-15, 1-10, or 1-5. The carrier ratio of the "solid dispersion" of the present invention is preferably as low as possible in consideration of bulk, wettability, and production cost, as long as dissolution, absorption, and stability are sufficient.

[0591] One embodiment of the "solid dispersion" of the present invention comprises, as active pharmaceutical ingredients, a compound represented by the above-mentioned general formula (I) or (II) or a pharmaceutically acceptable salt thereof, and HPMC and SLS, wherein the carrier ratio is in the range of 0.5-100, 1-50, 1-25, 1-20, 1-15, 1-10, 1-8, 1-5, 2-50, 2-25, 2-20, 2-15, 2-10, 2-8, 2-5, 3-50, 3-25, 3-20, 3-15, 3-10, 3-8, or 3-5, more preferably 1-25, 1-20, 1-15, 1-10, or 1-5. The carrier ratio of the "solid dispersion" of the present invention is preferably as low as possible in consideration of bulk, wettability, and production cost, as long as dissolution, absorption, and stability are sufficient.

[0592] One embodiment of the "solid dispersion" of the present invention contains as an active pharmaceutical ingredient a compound represented by the above general formula (I) or (II) or a pharmaceutically acceptable salt thereof, HPMC, and SLS, wherein the weight ratio of SLS to the active pharmaceutical ingredient (referred to as "SLS ratio" in this specification) is 0.05-50, 0.1-50, 0.1-25, 0.1-20, 0.1-15, 0.1-10, 0.1-8, 0.1-5, 0.1-4, 0.2-50, 0.2-25, 0.2-20, 0.2-15, 0.2 ~10, 0.2-8, 0.2-5, 0.2-4, 0.3-50, 0.3-25, 0.3-20, 0.3-15, 0.3-10, 0.3-8, 0.3-5, 0.3-4, 0.5-50, 0.5-25, 0.5-20, 0.5-15, 0.5-10, 0.5-8, 0.5-5 or 0.5-4, more preferably 0.1-10, 0.1-8, 0.1-5, 0.1-4, 0.5-10, 0.5-8, 0.5-5 or 0.5-4.

[0593] In the "solid dispersion" of the present invention, the compound represented by general formula (I) or (II) or a pharmaceutically acceptable salt thereof is preferably partially or entirely present in an amorphous form. Here, amorphous refers to a substance in a state in which there is short-range order between atoms or molecules of the compound represented by general formula (I) or (II) or a pharmaceutically acceptable salt thereof, but not long-range order like a crystal. In the present invention, amorphous can be confirmed by the presence of a halo pattern in powder X-ray diffraction.

[0594] In the present invention, preferably 50% by weight or more of the total weight of the compound represented by general formula (I) or (II) or a pharmaceutically acceptable salt thereof is present in an amorphous form, more preferably 80% by weight or more, more preferably 90% by weight or more, further preferably 95% by weight or more, further preferably 98% by weight or more, and 100% by weight may be present. The percentage of amorphous matter can be determined by X-ray diffraction.

[0595] The solid dispersion of the present invention can be produced by a known method per se, for example, a mixing and pulverization method (mechanical chemical method), a solvent method, or a melting method.

[0596] Here, the mixing and pulverizing method refers to mixing the compound represented by the general formula (I) or (II) or a pharmaceutically acceptable salt thereof with a carrier, and then performing the pulverization by a conventional method using a mixer and a pulverizer such as a ball mill or a hammer mill.

[0597] The solvent method refers to a method in which a compound represented by general formula (I) or (II) or a pharmaceutically acceptable salt thereof and a carrier are dissolved or suspended in a solvent (an organic solvent, water or a mixture thereof) and then the solvent is removed to precipitate a solid dispersion, or a solid dispersion is precipitated in the solvent.

[0598] The solvent can be removed by spraying (which can be classified into fluidized bed method, spray drying method (also called spray drying method), rotating bed method, stirring method or supercritical method, etc., depending on the embodiment), filtration method, evaporation method, freeze drying method and the like. The spraying method is preferred, among which the spray drying method is particularly preferred.

[0599] The solvent that can be used in the preparation of the solid dispersion of the present invention is preferably a pharmaceutically acceptable solvent, for example, ethanol, methanol, 2-propanol, n-propanol, butanol, acetone, 2-butanone, methyl ethyl ketone, methyl isobutyl ketone, tetrahydrofuran (THF), tetrahydropyran, 1,4-dihydrofuran ...methyl ethyl ketone, methyl isobutyl ketone, tetrahydrofuran (THF), tetrahydropyran, methyl ethyl ketone, methyl ethyl ketone, methyl isobutyl ketone, tetrahydrofuran (THF), tetrahydropyran, methyl ethyl ketone, methyl ethyl ketone, The solvents used in the reaction may be ethanol, methanol, acetone, THF, a mixture of ethyl acetate and water, or a combination of these solvents.

[0600] In the spray drying method, a solid dispersion can be produced by a method known per se, for example, a compound represented by general formula (I) or (II) or a pharmaceutically acceptable salt thereof and a carrier component are added to the above-mentioned solvent to form a solution or suspension, the solution or suspension is formed into a fine mist using centrifugal spraying based on a rotating disk or pressurized spraying based on a pressure nozzle, and the mist is sprayed into a drying medium (heated air or nitrogen) to obtain a solid dispersion as a powdered dry product. The various components used to constitute the solid dispersion are preferably dissolved in the solvent used.

[0601] In the spray drying method, the temperature of the drying medium is, for example, 50 to 120° C., preferably 50 to 90° C. The drying medium may flow in a certain direction, for example, at a speed of 0.2 to 0.6 m / s. 3 / min, preferably 0.3 to 0.5m 3 / min air volume (Drying Air) flows.

[0602] The melt method involves heating the compound represented by general formula (I) or (II) or a pharmaceutically acceptable salt thereof and a carrier component to a temperature above their melting point or softening point, stirring, or the like, to dissolve or disperse the mixture, followed by rapid cooling. Additives such as plasticizers such as triethyl citrate, polyethylene glycol, or triacetin, and surfactants may be added as needed. Production can be carried out using a stirring granulator equipped with a heating device.

[0603] The solid dispersion of the present invention produced by the above-mentioned production method can be converted into solid dispersion particles having any particle size by a known method, and the solid dispersion particles can be used directly as a powder or granule.

[0604] The pharmaceutical composition containing the solid dispersion of the present invention contains the above-mentioned solid dispersion and other pharmaceutically acceptable additives. As other additives, for example, binders, disintegrants, excipients, lubricants, etc. are appropriately combined and mixed in the required amounts to produce the pharmaceutical composition of the present invention.

[0605] As binders that can be used in the pharmaceutical composition of the present invention, methylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hypromellose, polyvinylpyrrolidone, gelatin, agar, alginic acid, sodium alginate, partially saponified polyvinyl alcohol, pullulan, partially alpha-starch, dextrin, xanthan gum, gum arabic powder, etc. are mentioned. Hydroxypropylcellulose, hypromellose, and polyvinylpyrrolidone are preferred. These can be used alone or as a mixture of two or more.

[0606] Examples of disintegrants that can be used in the pharmaceutical composition of the present invention include crystalline cellulose, carboxymethylcellulose (carboxymethylcellulose), croscarmellose sodium, carboxymethylcellulose calcium, low-substituted hydroxypropyl cellulose, cross-linked polyvinylpyrrolidone, hydroxypropyl starch, starch, partially alpha-starch, and sodium starch glycolate. Cross-linked polyvinylpyrrolidone, sodium starch glycolate, and cross-linked polyvinylpyrrolidone are preferred, and cross-linked polyvinylpyrrolidone is more preferred. The amount of the disintegrant used is preferably 5 to 30% by weight, more preferably 5 to 15% by weight, relative to the total weight of the pharmaceutical composition. Furthermore, when incorporated into tablets, the amount of the disintegrant in the tableting granules is preferably 1 to 10% by weight, more preferably 2 to 6% by weight.

[0607] Excipients that can be used in the pharmaceutical composition of the present invention can be incorporated into the kneaded product, granulated product, and subsequent powder. Examples include celluloses such as crystalline cellulose, ethyl cellulose, hydroxypropyl cellulose, low-substituted hydroxypropyl cellulose, and hydroxypropyl methylcellulose (such as hypromellose); starches such as corn starch, potato starch, wheat starch, rice starch, partially alpha-starch, and hydroxypropyl starch; sugars such as glucose, lactose, white sugar, refined white sugar, powdered sugar, trehalose, dextran, and dextrin; sugar alcohols such as (D-mannitol, xylitol, sorbitol, and erythritol); glycerol fatty acid esters; magnesium aluminometasilicate; synthetic hydrotalcite; anhydrous calcium phosphate, precipitated calcium carbonate, calcium silicate, calcium hydrogen phosphate hydrate; and inorganic salts such as sodium bicarbonate. Preferred examples include crystalline cellulose.

[0608] Lubricants that can be used in the pharmaceutical composition of the invention include stearic acid, sodium stearyl fumarate, magnesium stearate, calcium stearate, sucrose fatty acid esters, polyethylene glycol, light anhydrous silicic acid, hardened oil, glycerol fatty acid esters, talc, etc. Preferred lubricants are sodium stearyl fumarate, magnesium stearate, calcium stearate, and sucrose fatty acid esters. These can be used alone or as a mixture of two or more.

[0609] The pharmaceutical composition of the present invention is formulated into solid preparations such as tablets, capsules, granules, powders, and lozenges, or liquid preparations such as injections, by performing known formulation steps. The injections described above can also be provided as solid preparations and then prepared as injections upon use.

[0610] The present invention also has the effect of suppressing tableting obstacles, so the case where the solid preparation is a tablet is particularly preferred. In addition, these solid preparations can be coated as needed.

[0611] The content of the solid dispersion in the pharmaceutical composition of the present invention may be 10 to 95% by weight, preferably 30 to 90% by weight, and more preferably 60 to 85% by weight, relative to the total weight of the pharmaceutical composition.

[0612] The solid dispersion of the present invention or a pharmaceutical composition containing the solid dispersion can be administered orally or parenterally to humans or other mammals and is useful as a therapeutic agent for neuropathic pain, multiple sclerosis, antitussives, irritable bowel syndrome, inflammatory bowel disease, various allergies, and the like. As used herein, the term "treatment" encompasses not only treatment but also prophylaxis or preventative use.

[0613] One aspect of the present invention is a method for treating neuropathic pain, multiple sclerosis, antitussive, irritable bowel syndrome, inflammatory bowel disease, various allergies, etc., comprising the steps of administering a therapeutically effective amount of the solid dispersion of the present invention or a pharmaceutical composition containing the above-mentioned solid dispersion to a subject in need of treatment for neuropathic pain, multiple sclerosis, antitussive, irritable bowel syndrome, inflammatory bowel disease, various allergies, etc.

[0614] Another aspect of the present invention is the solid dispersion of the present invention or a pharmaceutical composition containing the solid dispersion, which is used for the treatment of neuropathic pain, multiple sclerosis, antitussive, irritable bowel syndrome, inflammatory bowel disease, various allergies, etc.

[0615] Another aspect of the present invention is the use of the solid dispersion of the present invention for the manufacture of therapeutic agents for neuropathic pain, multiple sclerosis, antitussives, irritable bowel syndrome, inflammatory bowel disease, various allergies, and the like.

[0616] The dosage of the solid dispersion of the present invention or the pharmaceutical composition containing the solid dispersion can be adjusted according to the content of the compound represented by general formula (I) or (II) or a pharmaceutically acceptable salt thereof in the solid dispersion of the present invention or the pharmaceutical composition containing the solid dispersion. Furthermore, the dosage can be appropriately determined based on the method of administration, the age, weight, sex, symptoms, and sensitivity of the subject to the drug, and can be adjusted based on the improvement of symptoms.

[0617] The dosage of the solid dispersion of the present invention or the pharmaceutical composition containing the solid dispersion is, for example, calculated as the content of the compound represented by general formula (I) or (II) or a pharmaceutically acceptable salt thereof for an adult, and is generally about 0.1 mg to 1000 mg per day for injection, and about 1 mg to 20,000 mg per day for oral administration. The dosage may be increased or decreased depending on age, symptoms, etc. The frequency of administration may be, for example, 1 to 3 times per day, preferably 1 to 2 times per day.

[0618] Example

[0619] Hereinafter, the present invention will be described in more detail based on Examples, Comparative Examples, and Test Examples, but the present invention is not limited thereto.

[0620] Example 1. Synthesis of compounds

[0621] According to the method described in Patent Document 1, naphthodiazepine Compound F2 (5-[4-[2-(trifluoromethyl)benzoyl]aminophenyl]-1H-naphtho[1,2-b][1,4]diazepine) -2,4(3H,5H)-dione), compound F48 (5-[4-(2-iodobenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione) and compound F57 (5-[4-[(2-ethylbenzoyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine These compounds are poorly soluble in water.

[0622] Example 2. Solid dispersion (1): Study of carrier

[0623] 2-1) Preparation of solid dispersion

[0624] Solid dispersions of Compound F48 (referred to as Solid Dispersions A to J depending on the carrier used) were prepared using the following 10 polymer-containing carriers. 5 mL of a methanol / dichloromethane mixture (all from Wako Pure Chemical Industries, Ltd.) (volume ratio: 3:10) was added to 125 mg of each carrier to dissolve the mixture. 250 mg of Compound F48 was dissolved in 100 mL of tetrahydrofuran (Wako Pure Chemical Industries, Ltd.), 2 mL of which was placed in a 10 mm x 10 mm test tube (As One), and 5 mL of the polymer solution was added. The carrier ratio (weight ratio of Compound F48 to carrier) for each solid dispersion was 25, and the SLS ratio (weight ratio of Compound F48 to SLS) for Solid Dispersion B was 8.3. The mixture was mixed using a vortex mixer until homogeneous and dispensed into four tubes (each containing 1.25 mg of Compound F48). A nitrogen stream was blown through these samples to distill off the organic solvent, and the samples were then dried under reduced pressure (Sato Vacuum, oil rotary vacuum pump) overnight to prepare solid dispersions. In addition, a sample without adding a carrier was prepared as a control.

[0625] Various carriers used in solid dispersions:

[0626] A: Hydroxypropyl methylcellulose (HPMC) (Shin-Etsu Chemical Co., Ltd., variety: TC-5R)

[0627] B: HPMC / sodium lauryl sulfate (SLS) (Tokyo Chemical Industry) (weight ratio 2:1)

[0628] C: Hydroxypropyl methylcellulose acetate succinate (HPMCAS) (Shin-Etsu Chemical Co., Ltd., MF)

[0629] D: Eudragit S100 (Evonik)

[0630] E:Eudragit E100 (Evonik)

[0631] F: Eudragit L100-55(Evonik)

[0632] G: Polyvinylpyrrolidone (PVP) (BASF)

[0633] H: PEG6000 (Wako Pure Chemical Industries, Ltd.)

[0634] I: Cross-linked polyvinylpyrrolidone (BASF)

[0635] J:Poloxamer P188(BASF)

[0636] 2-2) Dissolution test

[0637] Prepare 2 samples of 5 mL of the first solution (pH 1.2) of the Japanese Pharmacopoeia dissolution test and 2 samples of 5 mL of the second solution (pH 6.8) of the Japanese Pharmacopoeia dissolution test added to each prepared solid dispersion sample. After crushing the solid dispersion with a glass rod or a spatula, shake it at 37°C for 2 hours (EYELA, INCUBATOR FMS). Immediately add 200 μL of acetonitrile (Wako Pure Chemical Industries) to 200 μL of the sample solution filtered with a 0.22 μm filter. In addition, the dissolution test was also performed on the sample without adding a carrier as a control. The concentration of compound F48 in the dissolution solution was quantified by HPLC under the following conditions.

[0638] Quantitative conditions

[0639] Device: LC-2010CHT (manufactured by Shimadzu Corporation)

[0640] Column: YMC-Pack ODS-A, particle size 5 μm, inner diameter 4.6 mm, length 15 cm (YMC)

[0641] Detector: UV absorbance spectrophotometer (measurement wavelength: 250 nm)

[0642] Column temperature: 40°C

[0643] Mobile phase: 0.1% formic acid / acetonitrile mixture (1:1)

[0644] exist Figure 1The results of two repetitions of the test from the preparation of the various solid dispersions described above to the determination of the concentration of compound F48 in the dissolution solution are shown. The reproducibility of this test system is good. In the case of the first solution of the Japanese Pharmacopoeia dissolution test under acidic conditions, the dissolution of solid dispersion E using Eudragit E100, a basic polymer, as a carrier was significantly higher. On the other hand, solid dispersion A formed with only HPMC as a carrier had almost no effect on the dissolution of compound F48, but solid dispersion B formed with a carrier of a combination of HPMC and SLS showed a significant improvement in the dissolution of compound F48 in both the first and second solutions of the Japanese Pharmacopoeia dissolution test. When prepared using only SLS as a carrier according to the same process as above, compared to solid dispersion B formed with a combination of HPMC and SLS as a carrier, there was almost no effect on the dissolution of compound F48 (at SLS to compound F48 weight ratios of 5, 2, and 1, the dissolution concentrations of compound F48 were 31.4 μg / mL, 15.0 μg / mL, and 8.5 μg / mL, respectively). It should be noted that for both solid dispersions E and B, the concentration of compound F48 in the eluate reached its maximum value 10 to 20 minutes after the start of dissolution, and this state persisted for at least 2 hours.

[0645] 2-3) PK studies

[0646] Solid dispersions E and B were prepared using a rotary evaporator using the following method. Compound F48 was dissolved in THF to a concentration of 2.5 mg / mL. Each polymer was prepared to a concentration of 25 mg / mL in the same manner as above. Next, the compound F48 solution was added to the polymer solution while stirring at a weight ratio of 1:25 between the compound F48 and the carrier. After the resulting mixed solution was transferred to an eggplant-shaped flask, the organic solvent was distilled off using a rotary evaporator (Yamato Scientific, distillation apparatus). The eggplant-shaped flask was transferred to a desiccator and dried under reduced pressure using a vacuum pump for about 16 hours to obtain solid dispersions E and B.

[0647] Next, Solid Dispersion E dispersed in a 1% carboxymethylcellulose aqueous solution or Solid Dispersion B dissolved in water was orally administered once to fasted male rats (8 weeks old, Wistar (Crlj: WI), Charles River Laboratories, Japan) at a dose of 10 mg / kg of Compound F48 (n = 3 per group). As a control, crystalline Compound F48 was ground in an agate mortar and suspended in a 1% carboxymethylcellulose aqueous solution, and the resulting suspension was administered in the same manner.

[0648] Blood was collected over time before oral administration and 0.5, 1, 3, 5, 8, and 24 hours after oral administration. The concentration of compound F48 in the obtained plasma was measured by HPLC (Hitachi High-Technologies Co., Ltd.). The time to reach the maximum blood concentration (T max ), maximum blood concentration (C max ) and the area under the plasma concentration-time curve (AUC last )(Table 2). Solid dispersion E or B compared with the control, C max , AUC last All showed a significant absorption-improving effect. In addition, unlike the results of the in vitro dissolution test, the pharmacokinetic properties of solid dispersion B in plasma were better than those of solid dispersion E.

[0649] In summary, it was shown that the absorption of the present compound in the body can be improved by solid dispersion using Eudragi TE100 or a combination of HPMC and SLS as a carrier.

[0650] [Table 2]

[0651]

[0652] *: indicates the dosage calculated as compound F48.

[0653] Example 3. Solid dispersion (2): Study of mixing ratio based on dissolution test

[0654] By the same method as in Example 2, various solid dispersions with different mixing ratios were prepared based on solid dispersion E or B (Table 3: solid dispersions E1 to E3, B1 to B5).

[0655] [Table 3]

[0656]

[0657] The solid dispersion obtained was subjected to a dissolution test using the above method. Based on solid dispersion E, the carrier ratio was varied from 25 to 1. The dissolution rate in the first solution (pH 1.2) of the Japanese Pharmacopoeia dissolution test peaked at a carrier ratio of 5 and then decreased ( Figure 1 、 2 : Solid dispersions E, E1 to E3). On the other hand, when the carrier ratio was changed from 25 to 1 based on solid dispersion B, the dissolution rate in the second solution of the Japanese Pharmacopoeia dissolution test (pH 6.8) peaked at a carrier ratio of 5 and then decreased ( Figure 1 、 2: Solid dispersions B, B1-3). In addition, when the weight ratio of SLS contained in the carrier to compound F48, i.e., the SLS ratio, was varied from 8.3 to 0.3, the dissolution rate in the second solution of the Japanese Pharmacopoeia dissolution test (pH 6.8) peaked at an SLS ratio of 3.3 and then decreased ( Figure 1 、 2 : Solid dispersions B, B1-5).

[0658] Example 4. Solid Dispersion (3): Study of Mixing Ratio Based on PK Test

[0659] 4-1) Preparation of solid dispersion

[0660] Next, a PK test was performed to confirm the effect of the carrier ratio and the SLS ratio on the absorption in the organism. The preparation of various solid dispersions was carried out as follows using a spray dry method. 400 mg of compound F48 was dissolved in 160 mL of THF (Kanto Chemical, containing a stabilizer). In addition, 1.6 g of HPMC and 400 mg of SLS (domestic chemical) were dissolved in 80% (v / v) ethanol aqueous solution (100 mL). The two solutions were stirred and mixed for 1 hour to prepare a spray solution with a weight ratio of compound F48 / HPMC / SLS of 1:4:1 (carrier ratio of 5, SLS ratio of 1). The spray solution was pumped into a spray dryer (Yamato, Parvis MiniBed GB22) using a peristaltic pump. From the spray nozzle (Japan Spraying System Contract Co., Ltd., 2050SS, the inner diameter of the nozzle is 508 um) at an inlet temperature of around 85 ° C, an outlet temperature of around 60 ° C, and an air volume (Drying Air) of about 0.3 m 3 / min and spray drying was carried out under the conditions of a constant spray pressure. The primary dried product obtained was further dried for a second time using a vacuum dryer (at 40°C for about 1 day) to obtain 1.63 g of solid dispersion B5 in the form of a white powder. Solid dispersions B1, 5 to 8 shown in Table 4 were prepared in the same manner. In addition, solid dispersion B4 used a solid dispersion prepared by the method using the above-mentioned rotary evaporator. It should be noted that the prepared solid dispersion was subjected to powder X-ray diffraction analysis according to the following measurement conditions. The powder X-ray diffraction pattern of solid dispersion B5 is shown below. Figure 3 The halo pattern shown indicates that compound F48 is in a non-crystalline state.

[0661] Powder X-ray diffraction measurement conditions

[0662] Device: D2Phaser (BRUKER)

[0663] Cathode: Cu

[0664] Measuring angle: 2θ = 5 to 40°

[0665] Scan mode: PSD high-speed scanning

[0666] Counting time: 0.3 sec

[0667] Step width: 0.02°

[0668] Divergence slit: 1.0mm

[0669] Air scattering slot: 3.0mm

[0670] 4-2) PK study

[0671] Under normal conditions, various solid dispersions dissolved or suspended in water were orally administered to male rats (5 weeks old, CD(SD) (Cr1: CD(SD)), Charles River Laboratories, Japan) at a dose of 100 mg / kg of Compound F48 (n = 3 per group). Blood was collected over time at 0.5, 1, 3, 5, 8, and 24 hours after oral administration, and the concentration of Compound F48 in the obtained plasma was measured by HPLC. T was calculated based on the transition of the plasma concentration. max 、C max and AUC last (Table 4: n=3 for each group, mean ± standard deviation) When the carrier ratio of the solid dispersion was reduced from 5 to 3, the pharmacokinetic parameters of compound F48 (C max and AUC last ) decreased (refer to the values ​​of solid dispersions B6 and B5 with an SLS ratio of 1; and solid dispersions B7 and B8 with an SLS ratio of 0.3). In addition, when the SLS ratio was reduced from 3.3 to 0.3, the pharmacokinetic parameters of compound F48 (C max and AUC last ) decreased (refer to the values ​​of solid dispersions B4, B1, B5, and B8 with a carrier ratio of 5; and solid dispersions B6 and B7 with a carrier ratio of 3). It should be noted that a solid dispersion using Tween 80 (Kanto Chemical) instead of SLS (compound F48 / HPMC / Tween 80 weight ratio of 1:3.3:1.7) was prepared using the spray dryer used above and subjected to PK testing. The results showed that the absorption of SLS (solid dispersion B1) was not significantly decreased (C max :8783±572ng / mL,T max :3.7±1.2hr,AUC last : 123463±6401ng·hr / mL).

[0672] [Table 4]

[0673]

[0674] Example 5. Solid dispersion (4): Production based on spray drying method

[0675] 5-1) Preparation of spray liquid

[0676] 50 g of Compound F48 was dissolved in 17.98 kg of THF (Kanto Chemical, containing a stabilizer). Separately, 200 g of HPMC (Shin-Etsu Chemical) and 50 g of SLS (Kohiko Chemical) were added sequentially to a mixed solvent of 7.89 kg of ethanol (Kanto Chemical) and 2.5 kg of ion-exchanged water while stirring. 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 F48 / HPMC / SLS of 1:4:1.

[0677] 5-2) Spray drying and secondary drying

[0678] The prepared spray liquid was pumped into a spray dryer (CL-8i, Okawara Chemical Industry) via a peristaltic pump and spray-dried under the conditions of a stock liquid processing capacity of 4 kg / h, a spray gas pressure of 0.2 MPa in a two-fluid nozzle, an inlet temperature of 120°C, and an outlet temperature of 70°C. The obtained primary dried product (270.18 g) was further dried twice using a vacuum dryer (40°C / 60 hours), thereby obtaining 237.4 g of solid dispersion in the form of white powder (recovery rate 79.1%). The powder X-ray diffraction pattern of the solid dispersion B5 obtained in the above-mentioned manufacture showed the same halo pattern as the powder X-ray diffraction pattern of the solid dispersion B5 prepared in Example 4.

[0679] Example 6. Stability of solid dispersion

[0680] The powder X-ray diffraction of solid dispersion B5 prepared separately by spray drying was measured in the same manner as in Example 4 when stored at room temperature, in a light-shielded, sealed condition. Figure 3 As shown, since the diffraction pattern of the powder X-ray measured at the beginning of storage (0 month) and the diffraction pattern (halo pattern) of the powder X-ray measured about 34 months after the start of storage did not change, it was shown that compound F48 was in an amorphous state and stable even if it was stored for a long time. In addition, the physical stability of the compound F48 was investigated when it was stored in a light-shielding, open, heated and humidified state (stored for 1 week at 60 ° C and 85% humidity). As a result, no peak of the characteristic diffraction angle of the crystal of compound F48 was observed in the powder X-ray diffraction even after storage. In addition, the glass transition temperature (TA Instruments, Q2000) of the solid dispersion B5 was measured according to the manual of the same device, and the result was 100 ° C or more, suggesting that it is stable as an amorphous solid dispersion.

[0681] Example 7. Analgesic effect of solid dispersion

[0682] The analgesic effect of the solid dispersion was investigated using the Chung's variation model (Patent Document 1), a rat model of neuropathic pain. After establishing the Chung's variation model, solid dispersion B5 (vehicle ratio 5, SLS ratio 1; Compound F48 / HPMC / SLS = 1:4:1) prepared in the same manner as in Example 4 was suspended in water for injection on days 8-9. Non-fasted rats (Charles River Laboratories, Wistar, male, 7-8 weeks old) whose pain threshold was sufficiently reduced (paw withdrawal threshold ≤ 5 g) were orally administered with 1, 3, 10, or 30 mg / kg of Compound F48. An HPMC / SLS composition without Compound F48 was administered as a control. Following administration, pain thresholds were measured over time using the up-and-down method using von Frey filaments (STOELTING CO: TOUCH-TEST SENSORY EVALUATOR). As a result, the solid dispersion B5 showed a significant analgesic effect in the group in which the compound F48 was administered at a dose of 3 mg / kg or more compared with the control group ( Figure 4 In addition, in the 10 mg / kg administration group, a significant analgesic effect was shown from 3 hours to 8 hours after administration.

[0683] Example 8. Solid dispersion of compound F2

[0684] 8-1) Preparation of solid dispersion

[0685] A solid dispersion (carrier ratio 3, SLS ratio 0.6; Compound F2 / HPMC / SLS=1:2.4:0.6) was prepared using Compound F2 by the spray drying method described above as follows.

[0686] (1) Preparation of spray liquid

[0687] 25.0 g of Compound F2 was dissolved in 7250 g of THF (Kanto Chemical, containing a stabilizer). Separately, 60.0 g of HPMC (Shin-Etsu Chemical) was dispersed in 1776 g of ethanol (Kanto Chemical), and then 750 g of ion-exchanged water was added and stirred for 30 minutes. After confirming that the HPMC had dissolved, 15.0 g of SLS (Kohiko Chemical) was added and stirred for 20 minutes. The two solutions were mixed and stirred for 1 hour to prepare a spray solution with a weight ratio of Compound F2 / HPMC / SLS of 1:2.4:0.6.

[0688] (2) Spray drying and secondary drying

[0689] The prepared spray liquid was pumped into a spray dryer (CL-8i, Ohkawara Kakoki) via a peristaltic pump and spray-dried under the following conditions: a stock solution throughput of 3.9 kg / h, a two-fluid nozzle spray pressure of 0.2 MPa, an inlet temperature of 120°C, and an outlet temperature of 67°C. The resulting primary dried product (62.05 g) was further dried a second time in a vacuum dryer (40°C / approximately 8 hours), yielding 61.1 g of a solid dispersion as a white powder (recovery rate: 61.1%).

[0690] 8-2) Powder X-ray Diffraction of Solid Dispersion

[0691] The powder X-ray diffraction analysis of the solid dispersion of compound F2 was performed in the same manner as in Example 4. Figure 5 As shown, a halo pattern is presented, indicating that compound F2 is in an amorphous state.

[0692] 8-3) PK study of solid dispersion

[0693] Fasted male rats (8 weeks old, Wistar (Crlj: WI), Charles River Laboratories, Japan) were orally administered with a crystalline form of Compound F2 suspended in a 1% methylcellulose aqueous solution or a solid dispersion containing Compound F2 suspended in water for injection. The dose for each group was 10 mg / kg of Compound F2 (n = 3 per group). Blood was collected over time 0.5, 1, 2, 4, 6, 8, and 24 hours after oral administration, and the concentration of Compound F2 in the obtained plasma was measured using LC-MS / MS (MS / MS: API4000 SCIEX, LC: LC-20AD series Shimadzu Corporation). T was calculated based on the transition of blood drug concentration. max 、C max and AUC last (Table 5) As shown in Table 5, the pharmacokinetic parameters of compound F2 (C max and AUC last In addition, the solid dispersion of compound F2 has a good analgesic effect.

[0694] [Table 5]

[0695]

[0696] *: Indicates the dosage based on compound F2.

[0697] Example 9. Solid dispersion of compound F57

[0698] 9-1) Preparation of solid dispersion

[0699] A solid dispersion was prepared using Compound F57 by the spray drying method described above as follows (carrier ratio 3, SLS ratio 0.6; Compound F57 / HPMC / SLS=1:2.4:0.6).

[0700] (1) Preparation of spray liquid

[0701] 30.0 g of compound F57 was dissolved in 7710 g of THF (Kanto Chemical, containing a stabilizer). Separately, 72.0 g of HPMC (Shin-Etsu Chemical) was added to 2131 g of ethanol (Kanto Chemical) and dispersed therein. Then, 900 g of ion-exchanged water was added and stirred for 30 minutes. After confirming that the HPMC had dissolved, 18.0 g of SLS (domestic chemical) was added and stirred for 20 minutes. The two liquids were mixed and stirred to prepare a spray solution having a weight ratio of compound F57 / HPMC / SLS of 1:2.4:0.6 (a weight ratio of compound F57 to carrier of 1:3).

[0702] (2) Spray drying and secondary drying

[0703] The prepared spray liquid was pumped into a spray dryer (CL-8i, Ohkawara Kakoki) via a peristaltic pump and spray-dried under conditions of a stock liquid throughput of 3.9 kg / h, a two-fluid nozzle spray pressure of 0.17 MPa, an inlet temperature of 120°C, and an outlet temperature of 67°C. The resulting primary dried product (62.05 g) was further dried a second time in a vacuum dryer (40°C / approximately 9 hours), yielding 83.2 g of a solid dispersion as a white powder (recovery rate: 69.3%).

[0704] 9-2) Powder X-ray Diffraction of Solid Dispersion

[0705] The powder X-ray diffraction analysis of the solid dispersion of compound F57 was performed in the same manner as in Example 4. Figure 5 As shown, a halo pattern is presented, indicating that compound F57 is in a non-crystalline state.

[0706] Industrial applicability

[0707] Since the solid dispersion of the present invention exhibits high absorbability and storage stability in the body, it is useful as a therapeutic agent for neuropathic pain and the like.

Claims

1. A solid dispersion comprising a compound represented by the following general formula (I) or (II) or a pharmacologically acceptable salt thereof, In formula (I), R 1 and R 2 are 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 by 1 to 3 halogen atoms, an alkoxy group having 1 to 8 carbon atoms substituted by 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 having 1 to 8 carbon atoms in the alkoxy moiety, a phenyl group which may have a substituent, a pyridyl group which may have a substituent, or an aralkyl group having 6 to 10 carbon atoms in the aryl moiety and 1 to 8 carbon atoms in the alkylene moiety, or R 1 and R 2 Together with the benzene ring to which they are bonded, they can form a condensed 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 in the case where R 1 and R 2 Together and R 1 and R 2 The ring composed of the carbon atoms to which the respective groups are bonded may be substituted by 1 to 4 identical or different substituents 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 by 1 to 3 halogen atoms, an alkoxy group having 1 to 8 carbon atoms substituted by 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 having 1 to 8 carbon atoms in the alkoxy moiety, or an aralkyl group having 6 to 10 carbon atoms in the aryl moiety and 1 to 8 carbon atoms in the alkylene moiety, R 3 and R 4 are 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 by 1 to 3 halogen atoms, an alkoxy group having 1 to 8 carbon atoms substituted by 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 having 1 to 8 carbon atoms in the alkoxy moiety, or an aralkyl group having 6 to 10 carbon atoms in the aryl moiety and 1 to 8 carbon atoms in the alkylene moiety, R 5 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 having 6 to 10 carbon atoms in the aryl moiety and 1 to 8 carbon atoms in the alkylene moiety, R 6 and R 7 are 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 by 1 to 3 halogen atoms, an alkoxy group having 1 to 8 carbon atoms substituted by 1 to 3 halogen atoms, a halogen atom, a hydroxyl group or an amino group, X represents C, CH or N, Y represents N, NH or C(=O), in, When X is N, Y is not N or NH, In addition, when X is C or CH, and Y 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 represents an oxygen atom or a sulfur atom, A represents a benzene ring, a pyridine ring, a thiophene ring, a pyrimidine ring, a naphthalene ring, a quinoline ring, or an indole ring which may have 1 to 4 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 by 1 to 3 halogen atoms, an alkoxy group having 1 to 8 carbon atoms substituted by 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 having 6 to 10 carbon atoms in the aryl moiety and 1 to 8 carbon atoms in the alkylene moiety, a phenyl group, or a pyridyl group, or represents a bonding site, B represents N(R 8 )C(=O)、NHCONH、CON(R 9 )、NHC(=S)NH、N(R 10 )SO2、SO2N(R 11 ) or OSO2, Here, R 8 、R 9 、R 10 and R 11 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 having 6 to 10 carbon atoms in the aryl moiety and 1 to 8 carbon atoms in the alkylene moiety, D represents an alkylene chain having 1 to 6 carbon atoms which may have 1 to 4 substituents 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 hydroxy group, or an aralkyl group having 6 to 10 carbon atoms in the aryl moiety and 1 to 8 carbon atoms in the alkylene moiety, and further optionally having a double bond, or represents a bonding site, E stands for O, S, NR 12 or bonding sites, Here, R 12 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 having 6 to 10 carbon atoms in the aryl moiety and 1 to 8 carbon atoms in the alkylene moiety, G represents a group which may have 1 to 4 groups 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 by 1 to 3 halogen atoms, an alkoxy group having 1 to 8 carbon atoms substituted by 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 having 6 to 10 carbon atoms in the aryl moiety and 1 to 8 carbon atoms in the alkylene moiety, a phenyl group which may have a substituent, a pyridyl group which may have a substituent, an imidazolyl group which may have a substituent, oxazolyl, or the same or different substituents in the thiazolyl group which may have a substituent as a substituent, piperazine, piperidine, morpholine, cyclohexane, benzene, naphthalene, quinoline, quinoxaline, benzimidazole, thiophene, imidazole, thiazole, azole, indole, benzofuran, pyrrole, pyridine or pyrimidine, Furthermore, m represents an integer from 0 to 5, The following situations are not included: R 1 and R 2 When they do not form a ring together, X is C, Y is N, the double line composed of solid and dashed lines is a double bond, Z is an oxygen atom, A is a benzene ring, m is 0, B is C(=O)NH, E is a bonding site, and G is a phenyl group; R 1 、R 2 、R 4 、R 5 、R 6 and R 7 is a hydrogen atom, R 3 is a chlorine atom, X is C, Y is N, the double line consisting of a solid line and a dashed line is a double bond, Z is an oxygen atom, A is a bonding site, m is 1, B is NHC(=O), D is a methylene group or a bonding site, E is a bonding site, and G is a phenyl group; and R 1 、R 2 、R 3 、R 4 、R 5 、R 6 and R 7 is a hydrogen atom, X is N, Y is C(=O), the double line consisting of a solid line and a dotted line is a single bond, Z is an oxygen atom, A is a bonding site, m is 1, and B is CON(R 9 ), R 9 isopropyl, E is the bonding site, and G is a phenyl group which may be substituted by a methoxy group; In formula (II), represents a naphthalene ring, a quinoline ring, an isoquinoline ring, a tetrahydronaphthalene ring, an indane ring, a tetrahydroquinoline ring or a tetrahydroisoquinoline ring, Furthermore, these rings may be substituted by 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 by 1 to 3 halogen atoms, an alkoxy group having 1 to 8 carbon atoms substituted by 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 having 1 to 8 carbon atoms in the alkoxy moiety, or an aralkyl group having 6 to 10 carbon atoms in the aryl moiety and 1 to 8 carbon atoms in the alkylene moiety. R 3a and R 4a are 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 by 1 to 3 halogen atoms, an alkoxy group having 1 to 8 carbon atoms substituted by 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 having 1 to 8 carbon atoms in the alkoxy moiety, or an aralkyl group having 6 to 10 carbon atoms in the aryl moiety and 1 to 8 carbon atoms in the alkylene moiety, R 5a 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 having 6 to 10 carbon atoms in the aryl moiety and 1 to 8 carbon atoms in the alkylene moiety, R 6a and R 7a are 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 by 1 to 3 halogen atoms, an alkoxy group having 1 to 8 carbon atoms substituted by 1 to 3 halogen atoms, a halogen atom, a hydroxyl group, or an amino group, represents a benzene ring, a pyridine ring, a thiophene ring, a pyrimidine ring, a naphthalene ring, a quinoline ring, or an indole ring which may have 1 to 4 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 aralkyl group having 6 to 10 carbon atoms in the aryl moiety and 1 to 8 carbon atoms in the alkylene moiety, a phenyl group, or a pyridyl group, or represents a bonding site, B a N(R 8a )C(=O)、NHCONH、CON(R 9a )、NHC(=S)NH、N(R 10a )SO2、SO2N(R 11a ), or OSO2, Here, R 8a 、R 9a 、R 10a and R 11a 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 having 6 to 10 carbon atoms in the aryl moiety and 1 to 8 carbon atoms in the alkylene moiety, E a Indicates O, S, NR 12a or bonding sites, Here, R 12a 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 having 6 to 10 carbon atoms in the aryl moiety and 1 to 8 carbon atoms in the alkylene moiety, G a represents a group which may have 1 to 4 groups 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 by 1 to 3 halogen atoms, an alkoxy group having 1 to 8 carbon atoms substituted by 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 having 6 to 10 carbon atoms in the aryl moiety and 1 to 8 carbon atoms in the alkylene moiety, a phenyl group which may have a substituent, a pyridyl group which may have a substituent, an imidazolyl group which may have a substituent, oxazolyl, or the same or different substituents in the thiazolyl group which may have a substituent as a substituent, piperazine, piperidine, morpholine, cyclohexane, benzene, naphthalene, quinoline, quinoxaline, benzimidazole, thiophene, imidazole, thiazole, azole, indole, benzofuran, pyrrole, pyridine or pyrimidine, Furthermore, n represents an integer of 0-5.

2. The solid dispersion according to claim 1, wherein Contains a combination of hydroxypropyl methylcellulose (HPMC) and sodium lauryl sulfate (SLS), or aminoalkyl methacrylate copolymer E.

3. The solid dispersion according to claim 2, wherein Contains a combination of hydroxypropyl methylcellulose (HPMC) and sodium lauryl sulfate (SLS).

4. The solid dispersion according to claim 1, wherein The compound is B a It is an NHCO group or NHSO2 group bonded to the 3rd or 4th position of the benzene ring, n is 0 to 2, E a is the bonding site, G a The compound represented by the general formula (II) is a substituted phenyl group or a pyridyl group.

5. The solid dispersion according to claim 4, wherein B a is an NHCO group bonded to the 4-position of the benzene ring, n is 0, G a is a substituted phenyl group.

6. The solid dispersion according to claim 5, wherein G a is a trifluoromethyl group, a hydroxyl group, an alkyl group, or a halogen atom, G a is a substituted phenyl group.

7. The solid dispersion according to claim 1, wherein The compound or its pharmacologically acceptable salt is selected from the following (1) to (214): (1) 5-(4-Benzoylaminophenyl)-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (2) 5-[4-[(2-(trifluoromethyl)benzoyl]aminophenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (3) 5-[4-(3-bromobenzoyl)aminophenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (4) 5-[4-[4-(trifluoromethyl)benzoyl]aminophenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (5) 5-[4-(2-methylbenzoyl)aminophenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (6) 5-[4-(2,6-dimethylbenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (7) 5-[4-(2,6-dichlorobenzoyl)aminophenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (8) 5-[4-(3-chlorobenzoyl)aminophenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (9) 5[4-(2-phenylacetylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (10) 1-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-amino)phenyl]-3-phenylthiourea; (11) 5-[4-(2,3-dimethoxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (12) 5-[4-(2-methoxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (13) 5-[4-[(2-chlorophenylacetyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (14) 5-[4-(2,3-dimethylbenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (15) 5-[4-(2,5-dimethylbenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (16) 5-[4-(5-bromo-2-chlorobenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (17) 5-[4-(2,4-dichlorobenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (18) 5-[4-(2-hydroxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (19) 5-[4-(2,3-dihydroxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (20) 1-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-amino)phenyl]-3-phenylurea; (21) 5-[4-[(2,6-dichlorophenylacetyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (22) 5-[4-[(2-methoxyphenylacetyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (23) 5-[4-[(2-hydroxyphenylacetyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (24) 1-(2-chlorophenyl)-3-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-amino)phenyl]thiourea; (25) 5-[4-[3-(trifluoromethyl)benzoylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (26) 5-[4-[2-[(2-trifluoromethyl)phenyl]acetylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (27) 1-(2-chlorophenyl)-3-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-amino)phenyl]urea; (28) 5-[4-[(2-phenylpropionyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (29) 5-[4-(2-chloro-3-methoxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (30) 5-[4-(3-phenylpropionylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (31) 5-[4-[(1H-indole-3-carbonyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (32) 5-[4-(2-chloro-3-hydroxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (33) 5-[4-[(2-methyl-2-phenylpropionyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (34) 5-[4-(2-phenoxyacetylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (35) 5-[4-[2-(2-chloro-4-methoxyphenyl)acetylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (36) 5-[4-[(1-methyl-1H-imidazole-2-carbonyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (37) 5-[4-[2-(2,4-dichlorophenyl)acetylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (38) 5-[4-[2-(2-chloro-4-hydroxyphenyl)acetylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (39) 5-[4-(3-phenylpropenylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (40) 5-[4-[(3-pyridylacetyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-diketone hydrochloride; (41) 5-[4-(1H-benzimidazole-2-carbonylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (42) 1-[4-(2,3-dimethylbenzoylamino)phenyl]-7-methoxy-1H-1,5-benzodiazepine -2,4(3H,5H)-dione; (43) 5-[4-[(Benzoylamino)methyl]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (44) 5-[4-[(2-chlorobenzoylamino)methyl]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (45) 1-[4-(2,3-dimethylbenzoylamino)phenyl]-7-hydroxy-1H-1,5-benzodiazepine -2,4(3H,5H)-dione; (46) 5-[4-(2-chlorobenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (47) 5-[4-(2-bromobenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (48) 5-[4-(2-iodobenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (49) 5-[4-(2,3-dimethylbenzoylamino)-3-fluorophenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (50) 5-[4-[2-(2-methylphenyl)acetylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (51) 5-[4-[(quinoxalin-2-yl)carbonylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (52) 5-[4-[(5-methylthiophen-2-yl)carbonylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (53) 5-[3-[(2-chlorophenylacetyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (54) 5-[4-[(2,4,6-trimethylbenzoyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (55) 5-[4-(cyclohexylcarbonylamino)phenyl]-1,2,3,4,8,9,10,11-octahydronaphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (56) 1-[4-(2,3-dimethylbenzoyl)aminophenyl]-6-methyl-1H-1,5-benzodiazepine -2,4(3H,5H)-dione; (57) 5-[4-[(2-ethylbenzoyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (58) 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; (59) 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; (60) 1-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-amino)phenyl]-3-(2-methylphenyl)thiourea; (61) 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; (62) 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; (63) 5-[4-(2,3-dimethylbenzoylamino)-3-hydroxyphenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (64) 5-[4-(2-chloro-3-methoxybenzoylamino)phenyl]-1,3-dihydronaphtho[1,2-e]-1,4-diazepine -2-ketone; (65) 5-[4-[(4-dimethylaminobenzoyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (66) 5-[4-[2-(2,4-dichlorophenoxy)acetylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (67) 5-[4-[2-(2-methylphenoxy)acetylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (68) N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-yl)butyl]-2-chloro-3-methoxybenzamide; (69) 5-[4-(2-chloro-3-hydroxybenzoylamino)phenyl]-1,3-dihydronaphtho[1,2-e]-1,4-diazepine -2-ketone; (70) 5-[4-(2-acetylbenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (71) 5-[4-(2-tert-butylbenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (72) 5-[2-(2-iodobenzoyl)aminoethyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (73) 5-[3-[(2-iodobenzoyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (74) 6,7-dimethyl-1-[4-(2-iodobenzoyl)aminophenyl]-1H-1,5-benzodiazepine -2,4(3H,5H)-dione; (75) 5-[4-[(1-methylpiperidin-4-yl)carbonylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-diketone hydrochloride; (76) 5[4-[(Benzofuran-2-yl)carbonylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (77) 5-[4-[(1-methyl-1H-indol-3-yl)carbonylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (78) 5-[4-(2-propenylbenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (79) 5-[4-(2-propylbenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (80) 5-[3-fluoro-4-(2-iodobenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (81) 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; (82) 5-[4-[(2-isopropoxybenzoyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (83) 5-[4-[(3-methylthiophen-2-yl)carbonylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (84) 5-[4-(2-phenoxypropionylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (85) 5-[4-[2-(4-chloro-2-methylphenoxy)acetylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (86) 5-[4-(4-fluoro-2-trifluoromethylbenzoyl)aminophenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (87) 5-[4-(4-fluoro-2-methoxybenzoyl)aminophenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (88) 5-[4-(4-fluoro-2-hydroxybenzoyl)aminophenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (89) 5-[3-[(2-iodophenylacetyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (90) 5-[4-(2-methyl-2-phenoxypropionylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (91) 5-[4-(2-tert-butylbenzoylamino)phenyl]-1,3-dihydronaphtho[1,2-e]-1,4-diazepine -2-ketone; (92) 5-[4-[(3-dimethylaminobenzoyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (93) 5-[4-(4-iodo-2-methoxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (94) 5-[4-(6-fluoro-2-methoxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (95) 5-[4-(2-hydroxy-4-iodobenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (96) 5-[4-(6-fluoro-2-hydroxyamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (97) 5-[4-(2-fluorobenzoyl)aminophenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (98) 5-[4-[(2-dimethylaminobenzoyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (99) 5-[4-(2-methoxy-6-methylbenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (100) 5-[4-(2-hydroxy-6-methylbenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (101) 5-[4-[3-(2-methylphenyl)propionylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (102) 5-(4-phenylcarbamoylphenyl)-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (103) 5-(4-Benzylcarbamoylphenyl)-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (104) 5-[4-[3-(2-methylphenyl)acryloylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (105) 5-[4-[3-(2-chlorophenyl)propionylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (106) 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; (107) 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; (108) 5-[4-(2-chlorobenzyl)carbamoylphenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (109) 5-[4-[3-(2-chlorophenyl)acryloylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (110) 5-[4-(2-chlorophenyl)carbamoylphenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (111) 5-[4-(6-bromo-2,3-methylenedioxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (112) 5-[4-(6-bromo-2-methoxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (113) 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; (114) 5-[2-(2-iodobenzoyl)aminopyridin-5-yl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (115) 5-[4-(6-bromo-2-hydroxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (116) 5-[4-(6-chloro-2-methoxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (117) 5-[4-(2-iodobenzoylamino)phenyl]-1H-[1,4]diazepine 2,3-h]quinoline-2,4(3H,5H)-dione; (118) 5-[4-(6-chloro-2-hydroxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (119) 5-[4-(2-hydroxy-6-methoxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (120) 5-[4-[2-methoxy-6-(trifluoromethyl)benzoylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (121) 5-[4-[2-hydroxy-6-(trifluoromethyl)benzoylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (122) 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; (123) 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; (124) 5-[4-[2-chloro-5-(methylthio)benzoylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (125) 5-[4-[2-(methylthio)benzoylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (126) 5-[4-[3-(methylthio)benzoylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (127) 5-[4-[2-ethyl-6-methoxybenzoylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (128) 5-[4-(3-methylsulfonylbenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (129) 6-ethyl-1-[4-(2-iodobenzoyl)aminophenyl]-1H-1,5-benzodiazepine -2,4(3H,5H)-dione; (130) 5-[4-[2-ethyl-6-hydroxybenzoylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (131) 5-[4-(3-methanesulfinylbenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (132) 5-[4-(2-chloro-5-methanesulfinylbenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (133) 5-[4-(2-methanesulfinylbenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (134) 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)-diketone hydrochloride; (135) 5-[4-(2-chloro-6-methoxybenzoylamino)phenyl]-1,3-dihydronaphtho[1,2-e]-1,4-diazepine -2-ketone; (136) 5-[4-[[(3-chloropyridin-2-yl)carbonyl]amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (137) 5-[4-(2-chloro-6-hydroxybenzoylamino)phenyl]-1,3-dihydronaphtho[1,2-e]-1,4-diazepine -2-ketone; (138) 5-[4-(3-chloro-2-methoxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (139) 5-[4-[(3-methylpyridin-2-yl)carbonylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (140) 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; (141) 5-[4-(3-chloro-2-hydroxybenzoylamino)phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (142) 5-[4-[[(3-hydroxypyridin-2-yl)carbonyl]amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (143) 5-[4-[(3-vinylpyridin-2-yl)carbonylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (144) 5-[4-[(3-ethylpyridin-2-yl)carbonylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (145) N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho-[1,2-b][1,4]-diazepine -5-amino)phenyl]-2-nitrobenzenesulfonamide; (146) N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-amino)phenyl]benzenesulfonamide; (147) 3-Bromo-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-amino)phenyl]benzenesulfonamide; (148) N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-amino)phenyl]-3-methoxybenzenesulfonamide; (149) N-[3-(2-oxo-2,3-dihydro-1H-naphtho[1,2-e][1,4]diazepine -5-amino)phenyl]benzenesulfonamide; (150)N-[3-(2,4-dioxo-1,2,3,4-tetrahydronaphtho-[1,2-b][1,4]-diazepine -5-amino)phenyl]-2-nitrobenzenesulfonamide; (151)N-[4-(2,4-dioxo-1,2,3,4,8,9,10,11-octahydro-naphtho[1,2-b][1,4]-diazepine -5-amino)phenyl]-2-nitro-benzenesulfonamide; (152) N-[4-(2,4-dioxo-1,2,3,4,8,9,10,11-octahydro-naphtho[1,2-b][1,4]-diazepine -5-amino)phenyl]-N-methyl-2-nitrobenzenesulfonamide; (153)N-[3-(2,4-dioxo-1,2,3,4-tetrahydronaphtho-[1,2-b][1,4]-diazepine -5-amino)phenyl]-N-methyl-2-nitrobenzenesulfonamide; (154) 4-(2,4-dioxo-1,2,3,4,8,9,10,11-octahydronaphtho[1,2-b][1,4]diazepine -5-yl)-N-phenylbenzenesulfonamide; (155)N-[3-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b]-[1,4]diazepine -5-yl)phenyl]-2-naphthalenesulfonamide; (156) N-[3-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b]-[1,4]diazepine -5-yl)phenyl]-1-naphthalenesulfonamide; (157) N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-amino)phenyl]cyclohexanesulfonamide; (158) N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-amino)phenyl]-3-pyridinesulfonamide hydrochloride; (159)N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-amino)phenyl]-4-isopropylbenzenesulfonamide; (160)N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-amino)phenyl]phenylmethanesulfonamide; (161)N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-yl)phenyl]-3-pyridinesulfonamide; (162) N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-yl)phenyl]-2-naphthalenesulfonamide; (163) 3-Bromobenzenesulfonic acid 4-(2,4-dioxo-1,2,3,4,8,9,10,11-octahydronaphtho-[1,2-b][1,4]diazepine -5-yl)phenyl ester; (164) N-benzyl-N-[4-(1-benzyl-2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-amino)phenyl]-2-nitrobenzenesulfonamide; (165) N-benzyl-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-amino)phenyl]-2-nitrobenzenesulfonamide; (166) 3-Bromo-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-yl)phenyl]-N-methylbenzenesulfonamide; (167) N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho-[1,2-b][1,4]-diazepine -5-amino)phenyl]-N-methyl-2-nitrobenzenesulfonamide; (168) N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho-[1,2-b][1,4]-diazepine -5-yl)phenyl]-N-(2-hydroxyethyl)-2-nitrobenzenesulfonamide; (169) N-[4-(7-chloro-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepine] -1-yl)phenyl]benzenesulfonamide; (170) N-[4-(7-bromo-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepine -1-yl)phenyl]benzenesulfonamide; (171)N-[4-[(2,4-dioxo-7-(trifluoromethyl)-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepine -1-yl)]phenyl]benzenesulfonamide; (172) N-[4-(2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepine -1-yl)phenyl]benzenesulfonamide; (173) 1-(2-chlorophenyl)-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-amino)phenyl]methanesulfonamide; (174) 1-(3-bromophenyl)-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-amino)phenyl]methanesulfonamide; (175) N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho-[1,2-b][1,4]-diazepine -5-yl)phenyl]-2-trifluoromethylbenzenesulfonamide; (176) N-[4-(7-bromo-6-methyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepine -1-yl)phenyl]benzenesulfonamide; (177) 1-(2-chlorophenyl)-N-[4-(2,4-dioxo-1,2,3,4,8,9,10,11-octahydronaphtho[1,2-b][1,4]diazepine -5-amino)phenyl]methanesulfonamide; (178) 3-Bromo-N-[4-(2,4-dioxo-1,2,3,4,8,9,10,11-octahydronaphtho[1,2-b][1,4]diazepine -5-amino)phenyl]benzenesulfonamide; (179) N-[4-(2,4-dioxo-1,2,3,4,8,9,10,11-octahydronaphtho[1,2-b][1,4]diazepine -5-amino)phenyl]-3-methoxybenzenesulfonamide; (180) 1-(2-bromophenyl)-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-amino)phenyl]methanesulfonamide; (181)N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-yl)phenyl]-1-(2-methylphenyl)methanesulfonamide; (182) N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-amino)phenyl]-1-(2-nitrophenyl)methanesulfonamide; (183)N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-yl)phenyl]-2-phenylethanesulfonamide; (184) 1-(2,3-dichlorophenyl)-N-[4-(2,4-dioxo-1,2,3,4,8,9,10,11-octahydronaphtho[1,2-b][1,4]diazepine -5-amino)phenyl]methanesulfonamide; (185) 1-(2-chlorophenyl)-N-[4-(2,4-dioxo-7-methoxy-1H-benzo[1,2-b][1,4]diazepine -1-yl)phenyl]methanesulfonamide; (186) 1-(2-chlorophenyl)-N-[4-(2,4-dioxo-7-hydroxy-1H-benzo[1,2-b][1,4]diazepine -1-yl)phenyl]methanesulfonamide; (187) 1-(4-chlorophenyl)-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-amino)phenyl]methanesulfonamide; (188) 1-(2-chlorophenyl)-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-yl)benzyl]methanesulfonamide; (189) 1-(2-chlorophenyl)-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-yl)-2-methoxyphenyl]methanesulfonamide; (190) 1-(2-chlorophenyl)-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-yl)-2-hydroxyphenyl]methanesulfonamide; (191) 1-(2,6-dichlorophenyl)-N-[4-(2,4-dioxo-1,2,3,4,8,9,10,11-octahydronaphtho[1,2-b][1,4]diazepine -5-amino)phenyl]methanesulfonamide; (192) 1-(2-chlorophenyl)-N-[4-(2,4-dioxo-6-methyl-1H-benzo[1,2-b][1,4]diazepine -1-yl)phenyl]methanesulfonamide; (193) 1-(2-chlorophenyl)-N-[4-(2,4-dioxy-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-amino)propyl]methanesulfonamide; (194) 1-(2-chlorophenyl)-N-[2-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-yl)ethyl]methanesulfonamide; (195) N-[4-(2,4-dioxo-1,2,3,4,8,9,10,11-octahydronaphtho[1,2-b][1,4]diazepine -5-yl)phenyl]-1-(2-iodophenyl)methanesulfonamide; (196) 1-(2-chlorophenyl)-N-[4-(2,4-dioxo-1,2,3,4,8,9,10,11-octahydronaphtho[1,2-b][1,4]diazepine -5-yl)phenyl]-N-methylmethanesulfonamide; (197) 1-(2-chlorophenyl)-N-[4-(2-oxo-2,3-dihydro-1H-naphtho[1,2-e][1,4]diazepine -5-amino)phenyl]methanesulfonamide; (198) 1-[(2-trifluoromethyl)phenyl]-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-yl)phenyl]phenyl-N-methylmethanesulfonamide; (199) 1-(2-ethylphenyl)-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-yl)phenyl]phenyl-N-methylmethanesulfonamide; (200) 1-(2,3-dimethylphenyl)-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-yl)phenyl]phenyl-N-methylmethanesulfonamide; (201) 2-(2-chlorophenyl)-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-yl)phenyl]phenyl-N-methylethanesulfonamide; (202) 1-(2-nitrophenyl)-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-yl)phenyl]phenyl-N-methylmethanesulfonamide; (203) 1-(2-aminophenyl)-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-yl)phenyl]phenyl-N-methylmethanesulfonamide; (204) 1-(2-dimethylaminophenyl)-N-[4-(2,4-dioxo-1,2,3,4-tetrahydronaphtho[1,2-b][1,4]diazepine -5-yl)phenyl]phenyl-N-methylmethanesulfonamide; (205) 5-[4-[(pyridin-4-yl)carbonylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-diketone hydrochloride; (206) 5-[4-[2-[(pyridin-3-yl)oxy]acetylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-diketone hydrochloride; (207) 5-[4-[(pyridin-3-yl)carbonylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-diketone hydrochloride; (208) 5-[4-[(2-methylpyridin-3-yl)carbonylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-diketone hydrochloride; (209) 5-[4-[(2-chloropyridin-3-yl)carbonylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (210) 5-[4-[2-[(pyridin-2-yl)oxy]acetylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (211) 5-[4-[[4-(trifluoromethyl)pyridin-3-yl]carbonylamino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione; (212) 5-[4-[(2-chloropyridin-3-yl)carbonylamino]phenyl]-1H-[1,4]diazepine 2,3-f]isoquinoline-2,4(3H,5H)-dione; (213) 5-[4-[(2-chloropyridin-3-yl)carbonylamino]phenyl]-8,9,10,11-tetrahydro-1H-[1,4]diazepine 2,4(3H,5H)-dione; and (214) 5-[4-[(2-isopropylbenzoyl)amino]phenyl]-1H-naphtho[1,2-b][1,4]diazepine -2,4(3H,5H)-dione.

8. The solid dispersion according to claim 1, wherein The compound or a pharmacologically acceptable salt thereof is amorphous.

9. The solid dispersion according to claim 1, wherein The carrier ratio is 1 to 25.

10. The solid dispersion according to claim 3, wherein The SLS ratio is 0.1 to 10.

11. A method for producing the solid dispersion according to claim 1, characterized in that: Produced by spray drying.

12. A pharmaceutical composition comprising the solid dispersion according to claim 1. The pharmaceutical composition according to claim 12 , which is a solid preparation.

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