JPS63132891A - Tricyclic compound - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention provides novel tricyclic compounds, particularly pyrido[3,2,
1-ij]-]1.3.4-Benzoxadiazine derivatives, methods for their preparation, pharmaceutical compositions containing these compounds, and intermediates useful in the preparation methods.

More specifically, the present invention provides a method for formula -a (1), in which R1
is a hydrogen atom or a carboxy group:! 1 group, R2 represents a lower alkyl group which may be substituted with a hydrogen atom or a halogen atom, and R3 and R4 are each independently substituted with a hydrogen atom, a hydroxyl group, or a substituted or unsubstituted amine group. represents a lower alkyl group which may be substituted; X represents a halogen atom; and R5 and R
5 each independently represents a hydrogen atom, or a lower alkyl group optionally substituted with a hydroxyl group, a lower alkoxy group, or a substituted or unsubstituted σ-substituted amine group: or R5
and R6 may be combined with adjacent nitrogen atoms to form a 5- to 7-membered heterocycle, and the heterocycle may be substituted with one or more substituents at the carbon atom, Furthermore, the heterocycle is -NR'-2-〇-1-S
-1-SO-1-SOZ- or -NRfuC○-[
Here, R7 is a hydrogen atom, a lower alkenyl group, an optionally substituted lower alkyl group or an aralkyl group, or a single-stage formula (II), -(CH2)ncOR" (n) (in the formula, n
is O~4, R6 is a hydrogen atom, a lower alkoxy group,
Or rfLi! A novel pyrido useful as an active ingredient of an antibacterial agent [3,2,1-i j ] -1,3,4-benzoxadiazine derivatives and pharmaceutically acceptable salts thereof,
and hydrates or solvates of the compounds of formula (1) and their salts.

Hereinafter, the substituents in the above formula (1) will be explained in more detail;
Unless otherwise specified, the term "lower" preferably refers to 7 carbon atoms.
It means a carbon chain containing up to

Explanation of R’: R1 is a hydrogen atom or a carboxy protecting group.

In the above, the carboxy protecting group is, for example, a methyl group,
Represents a lower alkyl group such as ethyl group, n-propyl group, t-butyl group; other meanings include, for example, lower alkyl/yloxyfurkyl group (e.g. acetoxymethyl group,
Piparoyloxymethyl group, 1-7cetoxyethyl group and 1-pivaloyloxyxf i); low alkoxycarbonyloxyalkyl group (e.g. methoxycarbonyloxymethyl group, 1-ethoxycarbonyloxyethinosyl group and impropoxycarbonyloxyethyl group); (5-methyl-2-oxo-1,3-dioxo-) 4-yl)methyl group; or a lower alkalyl/7minomethyl group (eg, aceto7midomethyl group), which can be easily hydrolyzed in vivo. Other ester groups such as benzyl, cyanomethyl, 7-enacyl, 7-enyl and the like may also be used.

Description of R2: R2 is a lower alkyl group optionally substituted with a hydrogen atom or a halogen atom.

In the above, the lower alkyl group preferably contains 1 to 4 carbon atoms, particularly methyl, ethyl, n-propyl, isopropyl, n-butyl, etc., and the halogen atoms include fluorine, chlorine, Bromine, preferably heptad.

Description of R3 and R4: R3 and R4 are each independently a hydrogen atom or a lower alkyl group which may be substituted with a hydroxyl group or a substituted or unsubstituted amide group.

In the above, the low FL & furkyl group is preferably 1-
4 carbon atoms, especially methyl, ethyl, n-propyl, isopropyl, n-butyl and the like. The substituted amine 7 groups include cycloalkyl amine 7 groups such as trimethyl amine/group and trimethyl amine 7 group; lower fluoryl amine 7 groups such as methyl amine/group and ethyl amine 7 group; lower cyclic alkyl groups such as cyclopropyl amine 7 groups; There are 7 units, etc.

Description of R5 and R1: R5 and R6 are each independently a hydrogen atom, a hydroxyl group, a lower alkoxy group, or a substituted or unsubstituted 7
Indicates a lower alkyl group optionally substituted with a mino group;
Alternatively, Rs and R@ may be combined with adjacent nitrogen atoms to form a 5- to 7-shell polycyclic ring, in which the carbon atoms are substituted with one or more substituents. and the substituent is -NR
'-1-0-1-S-1-SO-1-SO,- or -NR'-CO-[:,:, R'l! , water 1k Lf
, < child, lower alkenyl group, rIi optionally substituted lower furkyl group or 7ralkyl group, or general formula (II), -(CHz)nCOR'' (II)
In the formula, n is θ to 4, and R1 is a hydrogen atom, a lower alkoxy group, or an optionally substituted amino, lower alkyl, or aryl group.

The groups shown above will be explained in more detail below.

The lower alkyl group is preferably a methyl group, ethyl group, n
-Propyl group, isopropyl group, n-butyl group, etc. 1-
A lower alkoxy group representing a group containing 4 carbon atoms is
The substituted amide group preferably represents a group containing 1 to 4 carbon atoms such as methoxy group, ethoxy group, n-propoxy group, impropoxy group, n-butoxy group, etc.
Diethylamino group, dimethylamino group, di-lower fulkylamino group of ethylmethylamino Jll, l; lower alkylamino group such as methylamino group, ethylamino group, n-propylamino group, isopropylamino group; cyclopropyl group, etc. represents a lower cyclic alkyl group, etc.

The 5- to 7-shell heterocycle formed by R5 and R6 represents a piperazinyl group, a morpholinyl group, a thiomorpholinyl group, a piperidyl group, a homopiperazinyl group, a pyrrolidinyl group, a pyrrolinyl group, a pyrrolyl group, an imidazolyl group, a triazolyl group, and the like.

Examples of substituents on one carbon atom of a multi-chain ring include hydroxyl group; lower flukoxy groups such as methoxy, ethoxy, and n-propoxy groups; 7 lower alkylamino groups such as cyclopropylamino groups; 7 lower cyclic alkylamino groups such as 7 cyclopropylamino groups; 7 dimethylamino groups, di-lower alkylamino groups such as diethylamino and ethylmethylamino groups; Alka/ylamino group; a benzylamino group which may be optionally substituted with a nitro group, an ami group, a halogen atom, a hydroxyl group and/or a lower alkoxy group, such as a (4-ami/benzyl) ami7 group; In the formula, Rso and R5' together with a lower alkyl group or a nitrogen atom are a saturated nitrogen-containing polycyclic ring of 5 to 8 shells), for example, a (tsumethylamino)methylene 7 group, (
hexahydro-IH-7zepin-1-yl) 7notylene amide 7 groups; benzylleoxycarbonyl 7mino group; 7-wire, halogen atoms such as chlorine and bromine; methyl group, ethyl group, n-propyl group, isopropyl group Lower alkyl groups such as; amino lower alkyl group, lower alkyl 7-minor lower alkyl group, lower cyclic alkyl 7-lower alkyl group,
di-lower alkyl 7minor-lower furkyl group, or lower alkali/ylamino-lower alkyl group, examples of these substituents include aminomethyl group, (ethylamino)
Methyl group, (ethylamino)methyl group, (n-propylamino)methyl group, (isopropylamine)methyl group,
(cyclopropyl amine/) methyl group, (dimethyl amine/
) Methyl group, (dimethylamino)methyl group, (ethylmethylamino)methyl group, acetylaminomethyl group, 2-
7minoethyl group, 2-(methylaminoneethylno)ethyl group, 2-(dimethylamino/)ethyl group, 2-
(trimethyl7mino)ethyl group, 2-(ethylmethylamino)ethyl group; hydroxy-lower alkyl group such as hydroxymethyl group, 2-hydroxyethyl group; optionally 7mino group, halogen atom, hydroxyl group and V/or A phenyl group optionally substituted with a lower alkoxy group, such as a 4-7minohenyl group, a 4-fluorophenyl group, a 4-
Chlorophenyl group, 4-hydroxyphenyl group, 4-/
) xyphenyl group; or pyrrolyl group, 4-methyl-
These include polycyclic rings such as a 1-piperazinyl group.

The lower fulkenyl group represented by R7 is, for example, an allyl group, a 3-methyl-2-butenyl group, a 2-butenyl group, a 1-methyl-2-7''ropenyl group, a 3-7'thenyl group, and the like.

The substituted alkyl group represented by R7 is, for example, 2-
Hydroxy-lower alkyl groups such as hydroxyethyl and 3-hydroxybutyl; Lower alkoxy-lower furkyl groups such as 2-methoxyethyl and 2-ethoxyethyl; Amino-lower alkyl groups such as 2-aminoethyl and 3-7 minoptyl; 2 -(methylami7)ethyl group, 2-(ethylamino)ethyl group, 3-(methylamino)butyl group, 3-
(ethylamino) lower alkyl such as butyl group, kylamino-
Lower alkyl group; 2-(dimethylamino/)ethyl group, 2
-Di-lower alkyl group such as (dimethylamino)ethyl group, 3-(trimethylamino)butyl group, 3-(dimethylamino)butyl group; 7-lower alkyl group; 2-fluoroethyl! , halogen-lower furkyl groups such as 3-fluoro-n-butyl group; carboxy-lower alkyl groups such as carboxymethyl group and 2-carboxyethyl group; sulfo-lower alkyl groups such as sulfomethyl group and 2-sulfoethyl group, etc. .

The optionally substituted aralkyl group R7 is, for example, a benol group, such as a 4-7 minobennol group, a 4-nitropentyl group, a 4-(dimethylamino)hensyl group, a 4-fluorobennol group, or a 4-chlorobennol group. , 3-nodoxybennol group, 4-nodoxybenzyl group, 3,4-tumethoxybennol group, one or more amine 7 groups, nitro group, lower alkyl amine 7 groups, di-lower alkyl amine 7 groups, halogen atom and/or Alternatively, it may be substituted with a lower alkoxy group or the like.

The amino group R'' may be unsubstituted or substituted, for example, by a lower alkyl group such as a methylamino group, a dinotylamino group, or a lower cyclic alkyl group such as a cyclopropylamino group.

The lower alkyl group R1 may be similarly unsubstituted or substituted, and examples of substituted alkyl groups represented by R1 include 2-carboxyethyl group, 3-carboxy-〇-propyl group. , 2-nodoxycarbonylethyl group, 2-ethoxycarbonylethyl group,
It is a group containing a carboxy group such as a 3-methoxycarbonyl-n-propyl group or a lower alkoxycarbonyl group.

The aryl group represented by R@ is preferably a phenyl group; examples of substituted aryl groups include 4-difluorophenyl group, 4-chlorophenyl group, 4-bromophenyl group, 4-nodoxyphenyl group. group, 2-carboxyphenyl group, 4-hydroxyphenyl! , 4-nitrophenyl i, 4-7mi/phenyl group, etc., preferably contains one or more halogen, lower alkoxy group, hydroxyl group, nitro group and/or amino group.

Particularly preferred groups represented by R7 are hydrogen, methyl group,
Ethyl group, n-propyl group, isopropyl group, 2-hydroxyethyl group, 2-meth)oxyethyl group, 2-amino/ethyl group, 3-7 mino-butyl group, 2-(methylamino)ethyl, 2- (ethylamino)-ethyl, 2-fluoroethyl group, carboxymethyl group, sulfomethyl group,
Allyl group, 4-7 minobenzyl group, 4-fluorobennol group, forcyl group, acetyl group, propionyl group, benzoyl group, 4-7 minobenzoyl group, 2-oxo-n-
Propyl group, 2-oxo-n-butyl group, 3-oxo-
n-butyl group, 3-oxo-n-bennal group, 3-carboxy-propionyl group, 3-ethoxycarbonylprobionyl group, 4-carboxy-butyl group, 7-enacyl group, 4'-7mino-7-enacyl group, ethoxy These include carbonyl group, methoxycarbonyl group, carbamoyl group, etc.

Particularly preferred groups represented by R'R' N- in formula (1) are 1-piperazinyl group, 4-methyl-1-
piperazinyl group, 3-methyl-1-piperazinyl group, 3
-722-1-piperazinylt3゜4-tmethyl-1
-piperazinyl group, 4-ethyl-1-piperazinyl group,
3-(4-7mino7enyl)-1-piperazinyl Jf,
4-n-propyl-1-piperazinyl group, 4-(2-fluoroethyl)-1-piperazinyl group, 4-allyl-1
-piperazinyl group, 4-(2-oxo-n-propyl)
-1-piperazinyl group, 4-(erboxymethyl)-1
-piperazinyl group, 4-(3-oxo-n-butyl)-
1-piperazinyl group, 4-(sulfomethyl)-1-piperazinyl i, 4-(4-7minobennol)-1-piperazinyl group, 4-(2-hydroxyethyl)-1-piperazinyl group, 3-oxo-1- Viveranonyl! , 4-7 enacyl-1-piperazinyl group, 4-(3-carboxypropionyl)-1-piperazinyl group, 4-7 cetyl-1
-piperazinyl group, 4-(4-nitrobenol)-1-
piperazinyl group, morpholinyl group, 2-methyl-4-morpholinyl group, 2,6-nomethyl-4-morpholinyl group,
4-thiomorpholinyl group, 1-oxide-4-thiomorpholinyl group, 1,1-dioxide-4-thiomorpholinyl group, 4-(aminomethyl)-1-piperidyl group, 4-
[(Methylamino)methyl 1-1-piperidyl group, 4-
Methoxy-1-piperidyl group, 4-hydroquine-1-piperinol group, 4-(1-pyrrolyl)-1-piperidyl group, 4-amino-1-piperidyl group, 4-(methylamino)-1-piperinol group, 4-(ethyl7mino)-1-piperidyl group, 1-homopiperazinyl group, 4-methyl-1
-Homopiperazinyl group, 3-7 mino-1-pyrrolinonyl group, 3-(methylamino)-1-pyrrolidinyl group, 3-
(Ethylami/)-1-pyrrolidinyl group, 3-(benzyloxycarbonylamino)-1-pyrrolinonyl group, 3
-(aminomethyl)-1-pyrrolidinyl group, 3-ami/
-4-phenyl-1-pyrrolidinyl group, 3-7 minnow 3
-Methyl-1=pyrrolinonyl group, 3-7minor-4-methyl-1-pyrrolidinyl group, 3-(4-7mi/benzylami/)-1-pyrrolidinyl group, 3-(4-methyl-1-
piberazinyl)-1-pyrrolinonyl group, 3-[(trimethylamino/)methyleneami/1-1-pyrrolidinyl M, 3
-[(methylamino)methyl]-1-pyrrolidinyl group,
3-[(methylamino)methyl]-4-phenyl-1-
pyrrolidinyl group, 3-methyl-3-[(methylamino)
/thyl 1-1-pyrrolinonyl group, 3-[(ethylamino)methyl]-1-pyrrolidinyl group, 3-(acetylaminomethyl)-1-pyrrolidinyl group, 3-[(dimethylamino)methyl]-1-pyrrolidinyl group, 3-[(ethylmethylamino)methyl]-1-pyrrolinonyl group, 3-7
Minnow 4-methoxy-1-pyrrolinonyl group, 3-methoxy-4-(methylamino)-1-pyrrolidinyl group, 3-
(Dithylamino)-4-me)xy-1-pyrrolidinyl i
, 3-7mi/-4-10low 1-pyrrolinonyl group, 3-
chloro-4-(methylamino)-1-pyrrolinonyl group,
3-chloro-4-(ethylamino)-1-pyrrolinonyl group, 3-7 minnow 4-fluoro-1-pyrrolidinyl group,
3-fluoro-4-(methylamino/)-1-pyrroli7nyl group, 3-(ethylamino)-4-fluoro-1-pyrrolidinyl group, 3-(aminomethyl)-4-chloro-1
-pyrrolidinyl group, 3-chloro-4-[(methylamine)methyl]-1-pyrrolidinyl group, 3-chloro-4-[
(ethylamino)methyl]-1-pyaridinyl group, 3-
(Ami/methyl) -4-fluoro-1-pyrrolidinyl group, 3-fluoro-4-[(methylami/)methyl]-
1-pyrrolidinyl group, 3-[(ethylamino)methyl 1
-4-fluoro-1-pyrrolidinyl group, 3-(aminomethyl)-4-methyl-1-pyrrolidinyl group, 3-methyl-4-[(methylamino)methyl 1-1-pyrrolidinyl group, 3-[(ethyl amino) methyl 1-4-methyl-1
-pyrrolidinyl group, 3-hydroxy-1-pyrrolinonyl group, 3-methoxy-1-pyrrolinonyl group, 3-chloro-
1-pyro17 nonyl N, 3-fluoro-1-pyrrolidinyl group, 3-hydroxy-4-methoxy-1-pyrrolinonyl group, 1-imidazolyl group, 4-methyl-1-imidazolyl group, 3-7mi/-4 -Hydroxy-1-pyrrolidinyl group, 3-(methylamino)-4-hydroxy-1-
Pyrrolidinyl group, 3-(ethylamino)-4-hydroxy-1-pyrrolidinyl group, 3-(tumethylamino)-4
-hydroxy-1-pyrrolidinyl group, [2-(tumethylamino)ethyl 1-methyami7 group, etc.

Description of X: X represents a halogen atom such as fluorine, chlorine or bromine, preferably a heptad or chlorine.

Novel pyrido [31211-1jl-1 of general formula (1)
13,4-benzoxacyanone derivatives and pharmaceutically acceptable salts and hydrates or solvates thereof are prepared according to the present invention by the following steps.

(,) General formula (l[[) In the formula, R1%R2, R3,1'<4 and X are formula (1)
and X' represents a halogen atom; the amino group, hydroxyl group and/or carboxy group in the formula may be protected. A compound represented by the general formula (■) R'' In the formula, R' and [7R' have the same meanings as those mentioned in formula (1), and are reacted with an amine represented by the following, and the protecting group is removed if desired; In the formula, R'%R2, Rs, Rs and X have the same meanings as stated in formula (1); and the amino group, hydroxyl group and/or carboxy group in the formula may be retained, A compound represented by the general formula (VI) K'' where R'' and R4 have the same meanings as stated in formula (1), or a carbonyl compound or a polymer thereof, 7
R7 is a hydrogen atom in order to react a setal, ketal or enyl ether and optionally remove the protecting group, or (c) to produce a compound of formula (1) in which R' is a group other than a hydrogen atom. The compound of formula (1) has a substituent R
? (d) R' and/or R'' is a lower alkyl group (or) a lower alkylamino group. In order to produce a compound of formula (1) which is a compound of the formula (1) which is a hydrogen atom or contains a 7-amino group, a 7-lower alkyl group or a hydroxyl group ( 1)
(e) R'R' N- is -SO- or -5O7
To produce a compound of formula (1) which is a 5- to 7-shell heterocycle containing -, the corresponding compound whose heterocycle contains -S- is subjected to an oxidation reaction, or (f) a free amino group, In order to produce a compound of formula (1) having a hydroxyl group and/or a carboxyl group, the protective group is removed from the corresponding compound of the formula (1) having a protected ami7 group, a hydroxyl group and/or a carboxyl group. , ([1> In order to produce a compound of formula (1) containing a halogen atom, use the formula (1) in which R1 is a carboxy protecting group.
halogenating a compound substituted with the corresponding hydroxyl group,
Optionally, removing the protecting group R1 or reducing the nitro group of the corresponding nitro-substituted compound of formula (1) to produce a compound of formula (H) containing the ami7 group, (i) a group of the formula (wherein R5° and R%+ are lower alkyl groups or together with the nitrogen atom represent a saturated N-heterocycle of 5 to 8\1); In order to produce the compound of (1), a formamide derivative of the general formula (■), in which R'' and R5' have the same meanings as described above, is obtained by converting the corresponding 7-mino-substituted compound of formula (+) to or by subjecting the carboxylic acid of formula (1) to a corresponding esterification to produce a compound of formula (1) in which R′ is a carboxy protecting group, or (to) When producing a pharmaceutically acceptable salt, hydrate or solvate of the compound of formula (1), or a hydrate or solvate of the salt, the compound of formula (1) is Convert to a salt, hydrate or solvate or a hydrate or solvate of a salt thereof.

Step A: It: General formula (Iff) as described in i, (wherein Ht, Rz, R3, R1 and I/Xl!, formula (1
); and X is a halogen atom; furthermore, the amino group, hydroxyl group and/or carboxy group in the formula may be protected) and the compound represented by the general formula NV) HN − A desired compound can be obtained by reacting with an amine represented by R' 1 (■) (in which R5 and R6 have the same meanings as stated in formula (1)) and optionally removing the protecting group. I can do it.

In step A, the compound represented by the formula (I[[) used as a starting material is a new compound, which can be synthesized, for example, according to the following reaction scheme a)* or b).

a) (Δ) ([1) (C) (D) (C) (J) (E)
CF) (in the formula, R2, Rco, R4
, X and VX' have the same meanings as above, and R' is a benzyl group, a methoxybenzyl group, a methoxymethyl group, a methoxyethoxymethyl group, a tetrahydropyranyl group, an allyl group, a -butyl group, a t- Represents a protecting group such as a butylzmethylsilyl group, an acetyl group, a benzoyl group; R' is a formyl group, an acetyl group, a trifluoroacetyl group, a benzoyl group, an ethoxycarbonyl group,
, 2.2-) represents a protecting group such as a dichloroethoxycarbonyl group, a phenoxycarbonyl group, a benyloxycarbonyl group, a t-butoxycarbonyl group, etc.; R''' is
When the compound of formula (IV) (representing a hydrogen atom or an ethyl group) contains an amine 7 group or a monoalkyl amine 7 group, these groups may optionally be formyl, acetyl, trifluoroacetyl, benzoyl, etc. may be protected by an amino-protecting group such as a group, an ethoxycarbonyl group, a 2,2.2-trichloroethoxycarbonyl group, a phenoxycarbonyl group, a benyloxycarbonyl group, or a t-butoxycarbonyl group.

The reaction between the compound of formula (III) and the amine of formula (IV) or an appropriately protected amine is optionally carried out in a solvent or without a solvent, and in order to sufficiently complete the reaction, sufficient It is preferred to increase the temperature by an amount of time. Preferred reaction temperatures are from about 30°C to 200°C, especially from 80°C to 150°C to obtain sufficiently fast reaction rates.
°C is preferred.

The reaction is preferably carried out using triethylamine, pyrinone, picoline, N,N-tumethylaniline, 1,8-diazabicyclo[5,4,01undec-7-ene, 1,4-diazabicyclo[2,2,2]octane, It is carried out in the presence of an acid binder such as an alkali metal hydroxide or an alkali metal carbonate. Alternatively, it is also possible to use an excess of amine of formula (1%') as acid binding agent.

Preferred solvents for this reaction are non-reactive solvents such as acetonitrile, alcohol, dimethylsulfoxide, dimethylformamide, dimethylacetamide, birinone, picoline, lutidine, N,N'-dimethylpropyleneurea. It is also possible to use mixtures of two or more solvents.

After completion of the reaction, the protecting group can be removed by a known method. For example, a formyl group can be removed by acid or base hydrolysis, preferably by base hydrolysis, and a benzyloxycarbonyl group can be removed by hydrolysis. Can be removed by decomposition.

Examples of starting materials produced by formula (1) include the following materials.

9.10-difluoro-3-methyl-7-oxo-2,
3-nohydro7H-pyrido[3,2,1-ijl-1
,3,4-benzoxanoanone-6-carboxylic acid, 9.10-cyclo3-methyl-7-oxo-2,3
-dihydro-7H-pyrido[3,2,1-1jl-1,
3,4-Benzoxanoacin-6-carboxylic acid, 9-chloro-10-fluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido [3,2゜1 i
jl -1t3 +4-benzoxadiazine-6-carboxylic acid, ethyl=9.10-difluoro-3-methyl-7-oxo-2,3-nohydro-7) summer-pyrido [3°2.1
ijl 1t3*4-benzoxadiazine-6-
Carboxy sheet, benol=9.10-difluoro-3-methyl-7-oxo-2,3-nohydro-7H-pyrido [3°2.1-
1jl-1v, L4-benzoxanoazine-〇-carboxylade, 9.10-difluoro-3-(2-fluoroethyl)-
7-oxo-2,3-dihydro-7H-pyrido[3,2
,1-ijl-1,3,4-benzoxacyanone-
6-carboxylic acid, 9.10-difluoro-2,3-dimethyl-7-oxo-2,3-dihydro-7H-pyrido [3,2,1'J]
11314-Benzoxadi7non-6-carboxylic acid, 9.10-difluoro-2-(hydroxymethyl)-3
-Methyl-7-oxo-2,3-dihydro-7H-pyrido[3,2,1ijl 1w3,4-benzoxadiazine-6-carboxylic acid, 9,lO-nofluoroa-2-[(tumethyl 7mino)methyl]-3-methyl-7-oxo-2,3-dihydro-
7H-pyrido[3,2,11jl-1-3,4-benzoxadiazine-6-carboxylic acid and 9.10-difluoro-2,2,3-trimethyl-7-oxo-2,3
-dihydro-7H-pyrido [3°2.1 ijl-1
w3*4-benzoxacy7syn-○-carboxylic acid, etc.

The amine of formula (IV) used in the above reaction is, for example,
Piperazine, 4-methylbiveratone, 3-methylbiperazine, 3-7enylbiverazine, 3-(4-7minophenyl)piperazine, 3-(4-nitrophenyl)piperazine, 4-(2-hydroxyethyl)piperazine, 7 moles olin, 2-methylmol 7-olin, 2,6-dimethylmol 7-olin, thiomol 7-olin, 4-(aminomethyl)piperazine, 4-[(methylamino)methylcopiveranone, 4-[(ethylamino)methylpyrrolinone, 4-
7minopiperidine, 4-(methyl 7mi/)piperinone,
4-(Dithylamino)piperinone, 4-(benzyloxycarbonyl7mi/)piperidine, 4-(benzyloxycarbonylmethylamino)piperinone, 4-(benzyloxycarbonylethylamino)piperinone, 4-hydroxypiperidine, 4-methoxy piperidine, 4-(
1-pyrrolyl)piperidine, homopiperidine, :3-[
(methylami7) methyl 1-pyrrolidine, 3-[(ethyl 7mino)methyl 1-pyrrolidine, 3-(acetylaminomethyl)pyrrolidine, 3-hydroxypyrrolidine, 3-7
Toxivirolidine, 3-7 minovirolidine, 3-(bennoloxycarbonyl7mino)pyrrolidine, 3-7mino-4-methylpyrrolidine, 3-(4-7minobenzulamino)pyrrolidine, 3-(methylamino)pyrrolinone,
3-(benzyloxycarbonylamino)pyrrolidine,
3-amino/-4-phenylpyrrolidine, 3-7 minoni 3
-Methylpyrrolidine, 3-(4-methyl-1-piperazinyl)pyrrolinone, 3-[(dimethylamino)methyleneami/]pyrrolidine, 3-[(methylamino)methyl]
-4-phenylpyrrolidine, 3-methyl-3-[(methylamino/)methyl-1-pyrrolidine, 3-(dityl7mino)pyrrolidine, 3-(pennoloxycarbonylethylamino)pyrrolisine, 3-[(dimethylamino) Methylpyrrolinone, 3-[(ethylmethylamino)methylpyrrolinone, 3-7nodo-4-methoxypyrrolidine, 3-amino-4-methoxypyrrolidine, 3-methoxy-4-(
methylamino)pyrrolidine, 3-(ethylamino)-4
-methoxypyrrolidine, 3-azido-4-hydroxypyrrolidine, 3-7mi/-4-hydroxypyrrolidine, 3
-(methyl7mi/)-4-hydroxypyrrolidine, 3-
(ethylamino)-4-hydroxypyrrolidine, 3-(
aminomethyl)-4-methylpyrrolidine, 3-methyl-
4-[(methylamino)methyl]pyrrolidine, 3-[(
Ethyl 7mino)methyl J-4-methylpyrrolidine, 3-
Hydroxy-4-7 toxypyrrolidine, 3-(7cetylaminomethyl)-4-hydroxypyrrolidine, imidazole, 4-methylamiguzole, N.

N,N'-)limethylethylenediamine, and the like.

Step B General formula (V) (wherein R1, R2, R5, R6 and (/X have the same meanings as described above; furthermore, an amino group, a hydroxyl group or a carboxy group in the formula may be protected), a carbonyl compound represented by the general formula (Vl) (wherein R3 and R4 have the same meanings as above) or a polymer thereof, an acetal, A desired compound can be obtained by reacting with a ketal or enol ether and removing the protecting group if desired.

In step B, the compound represented by formula (V) as a starting material is a new compound, and the compound represented by the above reaction scheme a)*
or b), or by reacting compound (H) or (Va) with an amine of formula (R').

When the carbonyl compound or its polymer, acetal, ketal or enol ether has an ami/or monoalkylamino substituent, the substituent may optionally be a group described as R in formulas (G) and (H). may be protected by

Optionally, the reaction can be carried out using tuoxane, tetrahydro7rane, acetonitrile, chloroform, trimethylformamide, dimethylsulfoxide, N.

It can be carried out in a solvent such as N'-dimethylpropylene urea or acetic acid. Mixtures of two or more solvents can also be used. Optionally, the reaction can be carried out using acetic acid, hydrochloric acid, sulfuric acid, methanesulfone fi, p) toluenesulfonic acid, pyridiniumyl-toluenesulfonate, ferric chloride, zinc chloride, chlorotrimethylsilane, Nafion-H (per7t). The reaction may be carried out in the presence of a catalyst such as sulfonic acid resin (manufactured by Aldrich Chemical Co., Ltd.), 7 Invalis)-15 (strongly acidic giant network structure resin (manufactured by Aldrich Chemical Co., Ltd. 91)).

The reaction temperature can be varied within a relatively wide range, and generally the reaction is carried out at a temperature of 20°C to 150°C.

In a preferred embodiment of the invention, about 1 mole or excess mole of carbonyl compound of formula (■) or its polymer, acetal, ketal or enol ether is used per mole of compound of formula (V).

The amino or monofulkylamino protecting group can be removed by a known method after the reaction, if desired.
For example, formyl groups can be removed by acid or acid group hydrolysis, preferably basic hydrolysis, and benzyloxycarbonyl groups can be removed by hydrolysis.

Examples of the starting materials represented by formula (V) are 6 and 7 below.
-difluoro-8-hydroxy-1-(methylamino)
-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid, ethyl 6,7-difluoro8-hydroxy-1-(
methylamino)-4-oxo-1,4-dihydro-3-
Quinoline carboxylate, benzyl 6.7-:) fluoro-8-hydroxy-1-(methylamino)-4-
Oxo-1,4-dihydro-3-quinolinecarboxylade, 6,7-dichloro-8-hydroxy-1-(methylamino)-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid, 6-chloro -7-Fluoro-8-hydroxy-1-(methylamino)-4-oxy-1,4-dihydro-carboxylic acid, 6.7-nofluoro-1-[(2-fluoroethyl)amino]- 8-hydroxy-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid, 6-fluoroC7-8-hydroxy-7-(1-imidazolyl)-1-(methylamino)-4-oxy-1,4 −
Dihydro-3-quinolinecarboxylic acid, ethyl; 6-chloro-8-hydroxy-7-(1-imigzolyl)-1-
(Methylamino)-4-oxy-1,4-dihydro-3
-ki/phosphocarboxilard, benzylco-6-fluoro-8-hydroxy-7-(1-
imidazolyl)-1-(methylamino/)-4-oxo-1,4-dihydro-3-quinolinecarboxylade, 6-fluoro-1-[(2-fluoroethyl)aminoco-8-hydroxy-7-(1- imidazolyl)-4-oxy-1,4-dihydro-3-chimerincarboxylic acid, 6-chloroa-3-hydroxy-7-(1-imidazolyl)-1-(methylamino)-4-oxy-1° 4-dihydro-3-quinolinecarboxylic acid, 6-fluoro-8-hydroxy'-'''1-(methylami/)-7-(4-methyl-1-piperazinyl)-4-oxy-1,4-dihydro- 3-quinolinecarboxylic acid, ?-(3,4-tumethyl-1-piperinonyl)-6-fluoro-8-hydroxy-1-(methylamino)-4-
Oxo-1,4-dihydro-3-quinolinecarboxylic acid, ? -[(3-[(benzyloxycarponylenamino)methyl]-1-pyrrolidinyl]-6-fluoro-8
-Hydroxy-1-(methylamino)-4=oxo-1
, 4-dihydro-3-quinolinecarboxylic acid, 7-[(3-[(benzyloxycarbonylamino)-
1-pyrrolidinyl]-6-fluoro-8-hydroxy-
1-(Methylamino)-4-oxo-1゜4-dihydro-3-quinolinecarboxylic acid, 7,-[3-(benzyloxycarbonylmethylami/)methyl]-4-methyl-1-pyrrolidinyl]-6- Fluoro-8-hydroxy-
1-(Methylamino)-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid, and 7-[3-[(bennoloxycarbonylamino)methyl]-4-chloro1-pyrrolidinyl]-6- Fluoro-8-hydroxy-1-(methylamino)-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid and the like.

Examples of compounds that can be reacted with the compound of formula (V) include carbonyl compounds such as formaldehyde, acetaldehyde, acetone, and methyl ethyl ketone; - 7-cetals such as dimethoxyethane, 1,3-dioxolane, glycolaldehyde methyl acecool, 7-methyl 7-minoacetaldehyde dimethyl 7-cetal; ketals such as 2,2-nomethoxypropane; and 2-methoxypropene, 2-trimethylsilyl These include near ethers such as oxypropene.

Step C: The groups R5 and R'N- in formula (1) are a 5- to 7-chain ring, the ring contains -NR', and R7 is a group other than hydrogen; For example, the piperazinyl group in the formula may be substituted on a carbon atom, R'' is a lower furkyl group or aralkyl group which may be substituted with a lower alkenyl group, or the general formula: - (CH2)ncoR' (11) (in the formula, n represents a number from 0 to 4, and R'' is a hydrogen atom, a lower alkoxy group, an optionally substituted amino group, a lower alkyl group, or an aryl group) ) is a group represented by] When producing a compound of formula (1) such as It can be synthesized by reacting with a suitable reagent.

The N-acylation (or N-acylation) reaction can be carried out as follows.

N-alkylated general formula (IM), (wherein R', R2, R, R (and X have the same meanings as above, and the piperazinyl group is substituted on the carbon atom) (1) General formula (X) EL'S-Y (X) c In the formula, Y is The leaving group R2O is +f1 as above
8 Wh A 6°+11 or (R
) is a group of R"C0-CH2CH2-) Go general formula (X I "I R・-Co-CH=CH2(X I) (wherein R' is a lower alkyl group or a lower alkoxy group) or (to obtain compounds in which R' is methyl or sulfomethyl) GiO formaldehyde and formic acid or an alkali metal bisulfite. .

N-Acylation: In order to obtain a compound of formula (1) in which R7 is HOOC-Z-Co-, the compound of formula (IX) is converted into a compound of general formula (X
II), in which Z represents a fullkylene chain or an arylene group having 2 or 3 carbon atoms, which may be optionally substituted.

If desired, after completion of all these reactions, the protecting groups, if any, may be removed.

In this manner, a desired compound can be synthesized by reacting a compound represented by formula (IX) with a compound represented by formula (X). Examples of the leaving group Y include halogen atoms such as chlorine, bromine, and iodine, acyloxy groups such as acetoxy groups, allylsulfonyloxy groups such as lower alkanesulfonyloxyphonyloxy groups such as methanesulfonyloxy groups, Alternatively, it is a phenoxy group, an optionally nitrated phenoxy group such as a 4-nitrophenoxy group, a succinimidoxy group, or a 7-talimidoxy group.

When the compound of formula (X) contains an amino group or a monoalkylamino substituent, those substituents are optionally protected by a group described for R'' in formulas (G) and (H) above. Optionally, this reaction can be performed using trimethylformamide, dimethyl hetacetamide, dimethyl sulfoxide, N, N' dimethylpropylene urea,
This can be carried out in a solvent such as dioxane, tetrahydrofuran, or pyridine.

It is also possible to use mixtures of two or more solvents.

This reaction preferably involves triethylamine, pyridine,
N,N-dimethyl 7-niline, 1,4-diazabicyclo[
2.2.2] octane, 1,8-diazabicyclo[5.
4.0] undec-7-ene, sodium hydride, an alkali metal hydroxide, an alkali metal carbonate, or the like.

The reaction temperature can be varied within a relatively wide range, and generally the reaction is carried out between about 0°C and 180°C IXO, preferably between 0°C and 110°C.

In a preferred embodiment of the present invention, 1 to 4 mol of the compound of formula (χ) per 1 mol of the compound of formula (IX),
Preferably 1 to 2 mol of compound is used.

In the present invention, examples of the compound of formula (X) include iodomethane, iodoethane, bromoethane, 1-iodobutane, 1-bromobutane, 1-iodopropane, 2-iodopropane, 1-fluoro-2-iodoethane, 1-
Iodo-2-methoxyethane, N-(2-iodoethyl)7ceto7mide, N-(2-"!doethyl)-N-methylacetamide, bromoacetic acid, allylbromide, 4-
Fluoropencyl bromide, acetic acid, formic anhydride, acetic anhydride, acetyl chloride, propionic anhydride, propionyl chloride, benzoic anhydride, benzoyl chloride, 4-[()lifluoroacetyl)ami71 benzoic anhydride, chloroacetone, 1-chloro-2-butanone, 7-enacyl chloride, 4-
Examples include 7cetyl 7mi/phenyl chloromethyl ketone, ethyl chloroformate, methyl chloroformate, chloroamethyl 4-nitrophenyl ketone, 4-nitrobennorpromide, and trimethylcarbamoyl chloride.

Alternatively, the desired compound may be a compound of the formula ([10] and
It can be synthesized by reacting with a Michael acceptor of formula (XI).

If desired, this reaction can be carried out in a solvent such as trimethylformamide, trimethylacetamide, dimethyl sulfoxide, dioxane, tetrahydrofuran, methanol, ethanol, furopanol, ethylene glycol mo/methyl ether, and the like. Mixtures of two or more solvents can also be used. The reaction temperature can be varied within a relatively wide range, and generally the reaction is carried out between about 0°C and about 170°C, preferably 50°C.
The temperature is between 140°C and 140°C. In a preferred embodiment of the invention, preferably 1 to 5 mol, particularly preferably 1 to 2 mol of a compound of formula (XI) are used per mol of compound of formula (LX).

The Michael acceptor used in the present invention is, for example, methyl vinyl ketone, ethyl vinyl ketone, or the like.

Alternatively, the desired compound (to obtain a compound of formula (1) in which R' is methyl or sulfomethyl) can be synthesized by reaction of formaldehyde with sulfoic acid or an alkali metal bisulfite with compound (IX). , this reaction is usually carried out under slight heating, for example at about 50°C to 100°C.

Furthermore, a desired compound can be synthesized by reacting an anhydride of formula (X II) with a compound of formula (IX).

If desired, this reaction can be carried out in a solvent such as pyridine, dimethylformamide, dioxane, tetrahydroctane, or the like. Mixtures of two or more solvents can also be used.

This reaction is preferably carried out in the presence of an acid binder such as triethylamine, birinone, N,N-tumethyl7-niline, 1,4-diazabicyclo[2,2,2]octane, alkali metal hydroxide, alkali metal carbonate, etc. It takes place below.

The reaction temperature can be varied within a relatively wide range and is generally about 0°C to 120°C, preferably 0°C to 100°C.
It is carried out between °C.

In a preferred embodiment of the present invention, % compound of formula (X rr ) per mol of compound of formula (II)! J1 mole or excess mole is used.

Examples of the anhydride used in the present invention include succinic anhydride, glutaric anhydride, N-bennoloxycarbonyl asparaic anhydride, N-benzyloxycarbonylglutamic anhydride, heptataric anhydride, and the like.

If desired, the protecting groups may be removed after the reaction by known methods, for example formyl groups may be removed by acid or base hydrolysis, preferably by base hydrolysis, benzyloxycarbonyl groups may be removed by It can be removed by hydrolysis. The protecting group may be removed before or after isolation of the product.

Step D: When producing compounds of formula (I) in which R5 and R6 are lower alkyl groups (or contain di-lower alkylamino groups or lower alkoxy groups), these compounds can be non-alkylated compounds, i.e. R5f;
It can be produced by lower alkylating a compound of formula (1) in which Yopi/mainly or R6 contains a hydrogen atom, ami 7 group, lower alkyl amine 7 group, or hydroxyl group, and N-alkylation is This can be carried out by reaction with a compound of the general formula (X[[), R''Y (XII[) (wherein, RIo is a lower alkyl group and Y is a leaving group).Leaving group teeth,
It is of the same type as that used in the compound of formula (X). This reaction can also be carried out by the same reaction when compound (IX) is fullkylated with compound (X) described above. O-alkylation is carried out similarly to N-alkylation, but preferably a proton acceptor such as an alkali metal hydride such as sodium hydride is added.

Step E: R5R'' N- contains -SO or -5O2-
When producing a compound of the formula (+>), which is a 7-shell compound ring,
These compounds are the corresponding oxygen scavenging compounds of formula (T),
That is, it can be produced by oxidizing a compound containing -8- in this heterocycle.

Oxidation can be carried out using organic or inorganic oxidizing agents. A variety of compounds that readily generate oxygen can be used as oxidizing agents; for example, mo/substituted organic peroxides (e.g., t.butyl hydroperoxide, alkanoyl hydroperoxide), performic acid, peracid Pa, etc. C,-
C, alkyl or alkanoyl hydroperoxides and phenyl-substituted derivatives of these hydroperoxides such as cumene hydroperoxide and perbenzoic acid can be used.

Optionally, for example 4-methylperbenzoic acid, 4-methoxy-perbenzoic acid, 3-chloroperbenzoic acid and monoperbenzoic acid.
C, -C, alkyl group, alkoxy group, such as tarlic acid, etc.
Peracids containing phenyl groups substituted with halogen atoms or carboxy groups can also be used. Many non-oxidizing agents such as hydrogen peroxide, ozone, permanganates such as potassium or sodium permanganate, atrium hypochlorite, potassium hypochlorite or ammonium hypochlorite, etc. hypochlorite, peroxy-sulfuric acid and peroxydisulfuric acid, and can also be used as oxidizing agents. Preferably 3-chloroperbenzoic acid is used. The oxidation is preferably carried out in a non-reactive solvent, e.g.
It is carried out in an aprotic, non-reactive solvent such as tetrahydrofuran, dioxane, methylene chloride, chloroform or 1m ethyl. This oxidation is generally -20
It is carried out in the temperature range from °C to -50 °C.

When an equimolar or slightly excess amount of oxidizing agent is used with respect to the starting material, the corresponding sulfoxide, i.e. -8
A compound of formula (1) having a double ring containing 〇- is obtained.

Increasing the amount of oxidizing agent by a factor of two or more by molar yields the corresponding sulfone, i.e., a compound of formula (1) with a -5o2-containing multi-stranded ring. The sulfone can be obtained by treating the corresponding sulfoxide with equimolar or more oxidizing agent.

Step F: When producing compounds of formula (1) having free ami7 groups, hydroxyl groups and/or carboxyl groups, these compounds have one or more protected ami7 groups, hydroxyl groups and/or carboxyl groups. It can be produced from the corresponding compound 2) having the following.

7/Protecting groups include, for example, lower alkanoyl groups such as acetyl groups; benzoyl groups; flucoquine carbonyl groups such as butoxycarbonyl or ethoxycarbonyl; substituted alkoxycarbonyl groups such as trichloroethoxycarbonyl; phenoxycarbonyl groups, benzyloxy An aralkyl group such as a carbonyl group, a p-nitrobenoloxycarboxylic group, a trityl group or a benzhydryl group; or a halogen-77reca/yl group such as trifluoroacetyl.

Amino protecting groups include 6-benzyloxycarbonyl groups and p- which can be removed by acid hydrolysis (e.g. t-butoxycarbonyl or trityl groups) or base hydrolysis (e.g. trifluoroacetyl groups).
The nitrobenoloxycarbonyl group can be removed by hydrolysis.

Amino protecting groups that are removed by acid hydrolysis can preferably be removed using lower alkane carboxylic acids even if halogenated.

First, formic acid or trifluoroacetic acid is used.

Acid hydrolysis is generally carried out at room temperature, but can also be carried out at somewhat higher or lower temperatures (e.g., temperatures from about 0<0>C to 40<0>C). Protecting groups that are removed under basic conditions are generally hydrolyzed with dilute aqueous alkaline solutions at 0°C to 30°C. The protecting group for the carboxy group has the same meaning as, for example, the carboxy protecting group mentioned in the explanation of R1 above.

Removal of these protecting groups can be carried out in known manner, for example by hydrolysis (benzyl group) or by acid or base hydrolysis. can be carried out during this reaction.

Special methods such as the following are also useful. decomposed; the L-butyl group is dissolved at about 0°C in a solvent such as methylene chloride or without solvent.
~removed by reaction with trifluoroacetic acid in the presence of anisole at room temperature; or the allyl group is removed by a palladium(0)-catalyzed transallylation reaction in the presence of sodium or potassium salts of 2-ethylhexanoic acid. For example, [(J, Org, Chem,)19
82, A-Gen, 587 Reference 1° Step G: When producing a compound of 2N) containing a halogen atom such as a compound in which R5R'N- is C1-σ)1-, the compound (e.g., R5R'N- is 110-04-).

It can be manufactured by soaking. The halogenating agent is preferably a thionyl halide, especially thionyl chloride, or phosphorus trichloride, phosphoryl chloride or phosphorus pentachloride.The reaction temperature is preferably from about 0<0>C to 80<0>C. The carboxyl group is preferably protected, for example by a benol group, and can be converted back into a free carboxyl group if desired subsequently, for example, by hydrolysis fraction M (removal of the benzyl group).

Step H: When producing a compound of formula (1) containing an amine 7 group, such as a compound where R5R'N- is 82N()-CIl□-Q-, the compound is substituted with the corresponding nitro group. It can be produced by reducing the 25p group of the compound of formula (1). Reduction can be carried out by hydrogenation under a noble metal catalyst such as palladium-carbon. This reaction can be carried out in water or a low a alcohol such as methanol or ethanol, optionally in a mixture with other solvents, and the reaction temperature is preferably around room temperature.

Process I: Convex R'R'N- is hull 1f, ), 14-Cl1=n-LX
) 4-, when producing a compound of formula (1) having a group represented by the formula % (in the formula R" and R51 has the same meaning as above), this compound is , the formula (
1) 7-mino group of the compound (for example, R5RsiC1++, N0-) and formamide represented by the general formula (■), R5OSI (in the formula, R5° and R51 have the same meanings as above) It can be produced by reacting the derivative with a reactive derivative.

As a reactive derivative of the compound of formula (■), trimethyl 7
Corresponding lower alkyl acecules such as setal can be used. This reaction is preferably carried out in a non-reactive medium such as dimethyl ether, trimethylformamide or trimethylsulfoxide. The temperature is preferably around room temperature, but lower or higher temperatures are possible, for example in the range of about 0°C to 100°C.

Step J: When preparing an ester of formula () in which R1 is a carboxy protecting group, the compound comprises a carboxylic acid of formula (I);
It can be synthesized by reacting with a corresponding halide, preferably an iodide or bromide containing the desired ester group.

This reaction can be accelerated by bases such as alkali metal hydroxides, alkali metal carbonates, or specific amines such as trimethylamine.

The ester is preferably carried out in a non-reactive solvent such as dimethylacetoamyl phoxide or, especially, trimethylformamide, and the reaction is preferably carried out at a temperature range of about 0<0>C to 40<0>C.

Steps: When producing a pharmaceutically acceptable salt of the compound of formula (1), or a hydrate or solvate of the salt, they can be prepared by known methods, e.g. It can be synthesized by reacting an acid with an equivalent amount of the desired base, or conversely by reacting the free base of formula (1) with an organic or inorganic acid. This reaction can be conveniently carried out in water or a solvent such as ethanol, methanol, acetone, etc. Temperature is not very important when producing salt. Salt formation is generally carried out at room temperature, but can also be carried out at temperatures somewhat above or below room temperature, for example in the range from 0°C to +50°C.

Examples of pharmaceutically acceptable acids useful in the above process include hydrobromic acid, sulfuric acid, phosphoric acid, nitric acid, Gidoro et al.
/1 Yū-11-1 acid, butyric acid, malic acid, tartaric acid, citric acid, ascorbic acid, maleic acid, hydroxymaleic acid, phenylacetic acid, benzoic acid, 4-ami7benzoic acid, anthranilic acid, 4-hydroxy Benzoic acid, salicylic acid, ami/salicylic acid, nicotinic acid, methanesulfonic acid, ethanesulfonic acid, hydroxyethanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, gluconic acid, glucuronic acid, lacturonic acid, aspartic acid and glutamic acid ;methionine, tryptophan, lysine, aruinine, etc.

The acid addition salt can be converted to the free form by treatment with a metallized hydroxide, a base such as ammonia.

A base addition salt of the compound of formula (1) is a compound of formula (1) and a gold sl such as an alkali or alkaline earth metal hydroxide.
It can be synthesized by reacting with a base or a specific amine.

Examples of metals used as cations are sodium, potassium, magnesium, calcium, etc. Examples of amines are noeta-7-lamine, N,N'-benzylethylenecyamine, choline, ethylenenoamine, and the like.

Acid or base addition salts of compounds of formula (1) differ from the corresponding free form in certain physical properties, such as solubility in water.

The compounds of formula (1) and their pharmaceutically acceptable salts can also exist in unsolvated forms or solvated forms, including hydrates.

Hydrates can occur during the manufacturing process or by gradual hydration of an initially anhydrous product due to its hygroscopic properties. Hydrate I! ? Embedded production produces completely or incompletely anhydrous products, e.g.
This can be carried out by maintaining the temperature at 0°C to 40°C and a certain humidity. Pharmaceutically acceptable solvates containing ethanol and the like are obtained during crystallization and the like.

Certain compounds provided by the present invention have asymmetric centers. The pure monoisomers, the pure L-isomers and mixtures thereof, including the racemate, are also encompassed by the invention.

The compounds provided by the present invention exhibit broad antibacterial activity against Gram-negative bacteria and mycoplasma, and can be used as agents for the treatment and prevention of infectious diseases.

The in vitro and in vivo antibacterial activity provided by the present invention is shown below.

1. "In vitro anti-seedling" (Sacrifice I) Representative of the present invention, pyrido [J +2 yl-iJ]-
The in vitro antibacterial activity of the 1+3,4-benzoxadiazine derivatives was tested by the Fuko agar dilution method [see Chemotherapy Gengen, 112G (1974) 16 Their minimum inhibitory concentrations (M I Cμg/aal) were Table 1
, shown in Table 2. The compounds used here were synthesized by the methods described in each example below.

Table-2 Antibacterial spectrum MIC (μg/ml) Anaerobic microorganism compound (Example 5 No. 30) Bacteroides fragilis AT
CC237450,780,20Bacteroicl
es fragilis NR25793,131,5
6Bacteroides fragilis NR2
5820,780,39Bacteroides fr
agilis NR2583Q, 39 Q, IQB
aeteroides fragilis NR258
40,780,78 Bacteroides dist
asonis NR25780,780,78Bact
eroides thetaiotaomicron
NR25881,560,788ifidobacte
rium adolescentis＾TCC1570
30,390,10 Ciostridiun botulinum NR2
6110,100,013Ciostridiui p
erfringens NR26120,390,10
Ciostridiua+ lIloniliform
e ATCC255460,780,10Fusoba
cteriua variu＋＊ ATCC85011
2,5PepLoeoccus prevotii
ATCC93211,560,39Peptocoe
cus variabilis ATCC149550
,780,20Peptostreptoeoceus
anaerobiusNR27430,39(1,0
13 Peopionibacterium aenes＾T
CC118280, 780°78 Myeoplas theory a Mycoplasna hominis NR2952
0,100,102, King! "Shifu liquid liao" υ pyrido synthesized in Example 5.30.65.66 described below
The in vivo antibacterial activity of 3,2,1-ij coco-,3,4-benzoxadiazine derivatives was
hia coli ML 4707, Pseudomonas
nas aeruginosa 4 au 542 and 5 treptococcus pneumoniae
Tested against 6-001 lethal infection. Weight 20g
ICR mice were infected with each bacterial solution by intraperitoneal administration. Test compounds were administered orally or subcutaneously at the same time as infection. Mortality was determined after 5 days, starting from death due to infection.
The effective dose (ED, ., mg/
Table 3).

Table-3 In vivo antibacterial activity in systemic infection in mice Example 5 0.06 0.11 13.4 10.
3 Example 30 0.10 0.62 57.0
65.9 Example 85-1.12 Example 66-0.51-3, :lJi Example 5.6.7.16.17.18.30.3 described below
The 50% lethal dose (LDso) of each of the compounds obtained in 6 and 56 was 2000 mg/kg or more.

The acute toxicity of these compounds was investigated by oral administration to CR mice.

The compounds provided by the present invention have a wide range of antibacterial activity against Durum-positive bacteria, Durham-negative bacteria, and mycoplasma, and are particularly effective against penicillins, cephalosporins,
It exhibits a wide range of antibacterial activity, even against microorganisms that have become resistant to various antibiotics such as aminoglycosides and tetracyclines.

Furthermore, the compounds provided by the present invention have low toxicity, strong and broad antibacterial activity. The protective efficacy of the compounds of the present invention in systemic bacterial infections in mice is significantly superior to the efficacy of already commercially available synthetic antibacterial agents. Therefore, the compounds of the present invention can be expected to have excellent effects when used for the prevention and treatment of diseases caused by Durum-positive bacteria, Durum-negative bacteria, and bacterial microorganisms in humans and animals. For example, it is possible to treat and/or prevent diseases caused by the following microorganisms or their combined contamination: 5taph
ylococcus, 5treptococcus,
Aerococcus, Enterococcus
, Microeoccus, Lactbacillus
us.

Bifidobacterium, Clostrid
ium, Enbacterium.

Peptocoecus, Peptostrepto
coeeus, Propionibacterium I
I, Escberishia, C1trobacter
Compylobacter, Enterobacter
er, Klebsiella, Proteus, Pse
udotaor+as, 5erratia, Salmo
nella, Shigella, 'VibriO1^e
romonas, tfaemophilus,
Ne1sseria, ＾cinetobacter
, ^Icaligenes, [1order
lla, Bacteroides, Fusoba
cterium, Mycoplasma and other microorganisms.

The invention further encompasses pharmaceutical compositions containing one or more compounds of the invention.

Compounds of the invention can be administered by a variety of common methods of administration.
It can be administered orally or parenterally to humans or animals.

Furthermore, the compounds of the present invention may be used alone or in combination with adjuvants, diluents, binders, lubricants, wetting agents, etc.
For example, tablets, granules, sugar-coated tablets, powders, capsules,
It can be used in the form of common pharmaceutical compositions such as gels, dry syrups, syrups, ampoules, suspensions, solutions, emulsions, ointments, pastes, creams, suppositories and the like.

Additionally, dissolution retarders, absorption enhancers, surfactants, etc. can be used as other additives for the formulation.

That is, all pharmaceutically acceptable nail types can be used.

The compounds of the present invention can be used alone or as a mixture of 2* or more different types of compounds, the total amount of the compounds being about 0.1-99.5% by weight of the total pharmaceutical composition, Preferably, it is 0.5 to 95%.

The pharmaceutical composition of the present invention may be formulated with a combination of a compound of the present invention or a mixture of compounds of the present invention and other medicinally effective compounds.

The daily dosage of the novel compounds provided by the present invention to patients varies depending on individual differences, species, body weight, and treatment status, but is generally 0.5 kg/kg body weight.
-500 sog, preferably 1-300 g.

The following examples are used to illustrate desirable methods of synthesizing the compounds of the present invention.

Sansho 1D11 different reference example No. 1 (a) 2.3-difluoro-6-ditrophenol (500mg) was dissolved in methanol (7mji), 5
% Pd/C (60 mg) was added thereto, and hydrogenation was carried out at room temperature and under normal pressure for 6 hours. The catalyst was filtered under a nitrogen stream, and the filtrate was concentrated under reduced pressure to obtain 414 mg of crude 2-7 minnow 5,6-difluorophenol.

(b) A mixture of the above amine (414+ur) and noethyl ethoxymethylene malonor (618 mg) was heated to 130° C. in five volumes under nitrogen atmosphere FHItX. The crystalline residue was triturated in ethanol and then collected by filtration to yield diethyl N-(3,4-7fluoro-2-hydroxyphenyl)7mi/methylene manor) 590B. Melt, 1
178-180°C, MSm/z 315 (M+).

This mother liquor was purified by silica gel chromatography using chloroform/acetone (20/1) as an eluent to obtain 59 g of crystals of the compound.

Knee! 2211t-f)-'*<J-le-) 1
) (e) Pencil bromide (30 μN) was mixed with diethyl N-(3,4-difluoro-2-hydroxyphenyl)aminomethylene malonor) (80 mg), W&potassium hydrcarbonate (70 mg) and dry dimethylformamide (1, The mixture was stirred at room temperature for 2 hours. The solvent was distilled off under reduced pressure, the residue was dissolved in dichloromethane, and the precipitate was filtered. The filtrate was washed with water. After drying with Glauber's salt, 6 was concentrated under reduced pressure.
After washing the crystalline residue with hexane, it was recrystallized from methanol to give diethyl, N-(2-benzyloxy-3,4
-nofluorophenyl)amy7methylene malonor) 90
I got +ur. Melting point 87°C, MSm/z405(M”
).

(d) A solution of the above Maronar) (280 mg) in diphenyl ether (2,8mj2) was added under a nitrogen atmosphere.
After heating at 250'C for 30 minutes, it was allowed to cool. The ethanol produced in the reaction was distilled off under reduced pressure, and the remaining dark brown 78
Pour the liquid into a silica gel (10 g) column, add benzene, dichloromethane and dichloromethane/acetone (30/
The mixture was sequentially eluted with the mixed solvent of 1).

The pure 7-lactone product was collected and the solvent was removed under reduced pressure.

The residue was washed with a mixed solvent of hexas and ethyl acetate, and ethyl=8-benzyloxy-6°7-77leo-a-4-human-a-x-3-ki/phosphocarpoxyler)
90 mg was obtained. The crude crystals could be used as they were in the next reaction, but analytically pure crystals could be obtained by recrystallization from methanol.

Melting point 200-201℃, MS m/z 359 (
M”).

I-2-1 He-3? ! Nib) Ni-noAζ2-(Lu-
2) Ethyl 6,7-difluoro-4,8-dihydroxy-3-key/linkerboxilade (300
Anhydrous potassium carbonate (308B) and then benol chloride (145 μm) were added to a solution of m8) in dry dimethylformamide (611 J) with stirring. The mixture was stirred at 55-65° C. for 11 hours and then diluted with water (30 Ugly 2). The mixture was subjected to solvent extraction with chloroform, dried over Glauber's salt, and then concentrated under reduced pressure. The residue was dissolved in acetone/chloroform (1/
After separation by chromatography using silica sol (7 g) using 20) as an eluent, recrystallization from methanol resulted in ethyl 8-benzyloxy-6,7-difluoro-
4-Hydroxy-3-ki/phosphocarboxilade 113
m) (obtained. Melting point 200-201. 'C1M5m/
z359 (M+).

Ethyl = 8-benzyloxy-6,7-pfluoro-1
-formylmethylamino)-4-oxo(e) Ethyl=8-pencyloxy-6,7-difluoro-4-hydroxy-3-quinolinecarboxylade (410+a
g), anhydrous potassium carbonate (315 mg) and dry dimethylformamide (10 ml) was stirred at room temperature for 3 hours, and then 0-(2,4-nonitrophenyl)hydroxylamine (260 mg) was added. The reaction mixture was stirred for an additional 6.5 hours at room temperature. Water (12 tall) was added to the residue obtained by distilling off the solvent under reduced pressure, and the mixture was stirred at room temperature for 3 hours. -6゜7-difluoro-4-oxo-1,4-nohydro-3-
Quinoline carboxylade 405B was obtained.

This precipitate can be used as is for the next reaction, but meta/
Analytically pure crystals could be obtained by recrystallization from a 3-glue. Melting point 143-144°C, MSm/y, 3 7 4
(M”).

(f) 98% gi f'l! (0,60aall) was added to acetic anhydride (1,51+1) at 0°C and the mixture was
After stirring at 50°C for 15 minutes and 15 minutes at 50°C, the mixture was cooled to 0°C. 98% formic acid (2,
1m) solution was added dropwise to this reaction solution. The mixture was stirred at room temperature for 2 days and then concentrated under reduced pressure.

The crystalline residue was recrystallized from ethanol to give ethyl 8-
410 mg of pencyloxy-6,7-nofluoro-1-(formylamino)-4-oxo-1,4-dihydro-3-quinoline was obtained. Melting point 188 1
．． 90'C5M5DI/2402 (M+).

(g) A mixture of the above formamide (400 ng), anhydrous potassium carbonate (275 mg) and dry trimethylformamide (17 sj) was stirred at room temperature for 1.5 hours.

Add methyl iosito (0,191111,) to this mixture.
was added and stirring was continued for an additional 2.5 hours. The solvent was distilled off under reduced pressure, and the residue was partitioned between water and chloroform. Existing RIM
After drying with Glauber's salt, it was evaporated to dryness under reduced pressure, and the residue was crystallized from ethanol to give ethyl 8-pennoloxy-6,
7-nofluoro1-(formylmethylamino)-4-
Oxo-1,4-dihydro-3-quinolinecarboxilade 335I+lI? I got it. Melting point 180-181℃,
M S m/z 41G (M”).

(h) Ethyl=8-benzyloxy-6,7-difluoro-1-(formylmethylamino)-4-oxo-
1,4-nohydro-3-quinoline carboxylar) (
330+eg) was dissolved in chloroform and 5% Pd/
C (50 Tsg) was added, and hydrogen decomposition was performed at room temperature and under normal pressure for 4 hours. After diluting the reaction mixture with methanol (14 ml), the catalyst was filtered, and the filtered catalyst was further washed with a mixed solvent of chloroform/methanol (1/1). The filtrates were collected and concentrated, and the residue was recrystallized from ethanol to give ethyl 6.7-nofluoro-1-(formylmethylamino)-8-hydroxy-4-oxo-1,4-
239 mg of dihydro-3-quinolinecarboxilade was obtained. Melting point 221-225°C (decomposition), MS n/z
326 (M+).

(i) A mixture of the above ester (210 logical g) and 0.5N sodium hydroxide solution (5.2 mA) was heated at 100° C. for 2 hours under a nitrogen atmosphere. Acetic acid (0°16mj
t) was added to the reaction mixture to make it acidic and a precipitate formed. This precipitate was collected by filtration, washed with water, and dried under reduced pressure. 1168 mg of carvone fi was obtained. This precipitate could be used as is for the next reaction, but analytically pure crystals could be obtained by recrystallization from ethanol. Melting point 248
-250°C (decomposition), MSm/z270 (M”).

Example 1 6,7-difluoro-8-hydroxy-1-(methylamino)-4-oxo-1,4- obtained in synthetic reference example (i) of carvone
A mixture of novitro-3-quinolinecarboxylic acid (105 mg), paraformaldehyde (150 +++ g) and dry nooxane (5-) was heated at 100° C. for 3 hours under nitrogen atmosphere. The solvent was removed under reduced pressure and dimethylformamide (2ml) was added to the residue. The mixture was stirred for 20 minutes and then filtered.

The filter cake was further washed with dimethylformamide and the filtrate was collected and evaporated under reduced pressure. The three residues were triturated in water, collected by filtration, and 9,10-difluoro-3-methyl-f-oxo-2,3-dihydro-7H-pyrid
,1-ijl-1,3,4-benzoxanoazine-6
-97+ og of carboxylic acid were obtained. Analytically pure samples were obtained by recrystallization from dimethylformamide. Melting point 290-292°C (decomposition), MS+n/z 282
(M”).

Example 2 9.10-difluoro-2,3-tumethyl-7-oxo-2,3-nohydrof H-pyrido r3.2°1-i'
-1+3+4-benzoxadiazine-6 reference example (i
) 6,7-difluoro-8-hydroxy-1 obtained in
A mixture of -(methylamino)-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid (50B), 90% acetaldehyde (1 ml) and diojusan (5 ml) was heated at 100°C for 3 hours under a nitrogen atmosphere. The reaction mixture was evaporated under reduced pressure to give 9,10-difluoro-2,3-
52 mg of dimethyl-7-oxo-2,3-dihydro-7H-pyrido[3°2.1-ijl-1,3,4-benzoxanoanone-6-carboxylic acid was obtained. Melting point 285~
289℃, MS gloss/z296 (M10).

Example 3 6,7-difluoro-8-hydroxy-1-(methylami/)-4-oxo-1,4- obtained in Reference Example (i)
Dihydro-3-quinolinecarboxylic acid (50 sgL glycolaldehyde noethyl acetal (45 μl) and pyridinium p-) luenesulfoner) (7 mg) was suspended in dry noxane (2+*l) and dissolved under a nitrogen stream for 1
Heated at 10°C for 5 hours.

The crystalline residue obtained by removing the solvent under reduced pressure was washed with water and methanol to give 9.10-difluoro-2-(hydroxymethyl)-3-methyl-7-oxo-2,3-
Nohydro 7H-pyrido [3,2゜1-iil-1v3
t4-benzoxadiazine-6-carboxylic acid 52I
I1g was obtained. Melting point 254-258°C (decomposed), MSm
/z312(M”).

Example 4 6,7-difluoro-8-hydroxy-1-(methylamino)-4-oxo-1,4- obtained in Reference Example (i)
Dihydro-3-quinolinecarboxylic acid (50 mg), trimethyl 7-minoacetaldehyde = dimethyl = 7 cetal (
37 kg) and p-) luenesulfonic acid, monohydrate (53
B) was suspended in dry noxane (2 theory P) and heated at 110° C. for 17 hours under a nitrogen atmosphere. The solvent was distilled off under reduced pressure, and the residue was recrystallized from methanol to give 9,10-nofluoro-2-[(dimethyl7mino)methyl]-3-methyl-7-oxo-2,3-dihydro-7H-pyrido. [3,
2,1-ijl-1* 314-benzoxacyanone-6-carboxylic acid-p-)luenesulfoner) 61 mg
I got it. Melting point 232-236°C (decomposed), FAB-MS
m/z340 (MH+).

Example 5 9,10-difluoro-3-methyl-oxo-2,3-dihydro-7H-pyrido[3,
2,1-ijl-1,3*4-benzoxanoanone-
6-carboxylic acid (30a+g), N-methylbiperanone (47 μl) and dry birinone (3tr1) were heated at 100° C. under nitrogen atmosphere for 9 hours. Pyridine was removed under reduced pressure and the residue was recrystallized from methanol. hand,
9-Fluoro-3-methyl-10-(4-methyl-1-
piveranonyl)-7-oxo-2,3-dihydro-7H
23 mg of -pyrido[3°2.1 1jl-1,3,4-benzoxacyanone-6-carboxylic acid was obtained. Melt, α
268-269℃ (decomposition), M S+s/z362 (
M”).

The following compounds were synthesized in a similar manner to Example 5.

Example 24 9,10-difluoro-3-methyl-7-oxo2,3-dihydro-7H-pyrido[3,
2,1-ij]-1,3,4-benzoxadiazine-
6-carboxylic acid (40 mg), 2-viverasonone (31
, 1-g), 1,4-diazabicyclo[2,2,2]octane (31,8 mg) and dimethyl sulfoxide (
1 mA> of the mixture at 130"C under a nitrogen atmosphere for 28.
Heated for 5 hours. After removing the solvent under reduced pressure, the residue was subjected to preparative TLC (silica sol; chloroform/methanol = 10
/1.5) and recrystallized from a mixed solvent of nochloromethane and methanol to obtain 9-fluoro-3-methyl-7.
-oxo-10-(3-oxo-1-piperazinyl)-
2,3-dihydro-7H-pyrido[3,2,1-'J]
-1+3H4-benzoxadiazine-6-carboxylic acid 6.3B was obtained. Melting point>300℃, FAB-MSm
/z363 (MH 10).

The following compounds were synthesized in a similar manner to Example 5 using the compounds obtained in Examples 2, 3 and V4 as raw materials.

Example 29 9,10-difluoro-3-methyl-twooxo-2,3-dihydro-7H-pyrid [3,
2,1-ijl-1,3-4-benzoxadiazine-
6-carboxylic acid (28 mg), 3-(pennoroxyca!levonylamino)pyrrolinone (94 mg) and dry birinone (3 ml) were heated at 100° C. for 3 hours under a nitrogen atmosphere. Pyridine was removed under reduced pressure and the residue was recrystallized from methanol to give 10-[3-(benzyloxycarbonylamino)-1-virolinonyl]-9-fluoro-
36 mg of 3-methyl-7-oxo-2,3-dihydro-7H-pyrido [3°2, 1-ijl=1.3.4-benzoxanoanone-6-carvone #] was obtained. Melting point 22
7”-230℃, M S Ifi/z482 (M”
>.

Example 30 10-[3-(benzyloxycarbonylamino)-1-pyrrolinonyl]-9-fluoro-3-methyl-7-oxo-2,3-dihydro-7H- obtained in Example 29
Pyrido [3,2,1-ijl-1゜3.4-benzoxadiazine-6-carboxylic acid (30 mg) was dissolved in dimethylformamide, 5% Pd/C (10 mg) was added, and the mixture was heated at room temperature and normal pressure. Hydrolysis was carried out for 4.5 hours. The catalyst was filtered off, and the filtrate was concentrated under reduced pressure. The residue was crystallized from methanol to give 1O-(3-amino-1-pyrrolidinyl)-
9-Fluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido[3,2,'1-ij]-1.3.
4-benzoxanoacune-6-carvone! 16 mg was obtained. Melting point 230-234°C (decomposition), MSm/z34
B(M”).

The following compounds were synthesized in a similar manner to Examples 29 and 30.

Example R5R6N-Melting point rIj crystal MS
m/z number °C Solvent wood FAII-MS Example 36 9-Fluoro-3-methyl-10- obtained in Example 7
(3-Methyl-1-piperazinyl)-7-oxo-2°3-nohydro7H-pyrido[3,2,1-ijl-1
y3w4-benzoxacyanone-6-carboxylic acid (6
A mixture of 0mg), 98% formic acid (11) and 35% formalin (1τof) was heated and stirred at 1oo-iio°C for 2 hours. After evaporating the reaction mixture under reduced pressure and dissolving in water,
Neutralized with 1N sodium hydroxide solution. It was extracted with chloroform, washed with water, and then dried with Glauber's salt.

The crystalline residue obtained by removing the solvent under reduced pressure was recrystallized from methanol to give 1O-(3,4-tumethyl-1-
piperazinyl)-9-fluoro-3-methyl-7-oxo-2,3-nohydro-7H-pyrido[3,2,1-i
, +1-iv3y4-benzoxadiazine-6-carboxylic acid 43B was obtained. Melting point 257-259°C, FAB-
MSm/z3 7 7 (MH+).

Example 37 9-fluoro-10-(3-hydroxy-1-pyrrolidinyl)-3-methyl-7-oxo-2,3-nohydro-7H-pyrido[3,2,1-ij
l-1,3,4-benzoxadiazine-6-carboxylic acid (100+++g) was dissolved in dry dimethylformamide (1
This was suspended in 60% sodium hydride, oil (30 mg), followed by methyl iositoide (40 μm).
) was added. After stirring this mixture at room temperature for 2 hours, 60%
Sodium hydride, oil (30B) and then methyl iodine (40 μm) were added, and stirring was continued at 45° C. for 3 hours. After removing the f# medium under reduced pressure, add cold water (2
1) and 0.5N sodium hydroxide solution (2.3ml)
) was added. This suspension was heated at 100°C for 2 hours.

After cooling to room temperature, it was neutralized with acetic acid and diluted with water.

The extract was extracted with chloroform, washed with water, dried over Glauber's salt, and concentrated under reduced pressure. The crystalline residue was dissolved in acetone/chloroform (1/9
) was separated using silica sol chromatography using the elution solvent. Recrystallized from methanol to give 9-fluoro-1
0-(3-methoxy-1-pyrrolidinyl)-3-methyl-7-oxo-2,3-dihydro-78-pyrido [3,
2,1-ijl-1,3,4-benzooxy azine-
1 g of 6-carboxylic acid 42II was obtained. Melting point 233-23
4°C, FAB MS m/z 364 (MH+).

Example 38 9-fluoro-10-(4-hydroxy-1-piperidyl)-3-methyl-7-oxo- obtained in Example 13
2,3-dihydro-7H-pyrido[3,2,1-ijl
Using -1,3,4-benzoxacyanone-6-carboxylic acid as a raw material, 9-fluoro-10-(4-methoxy-1-piperinor)-3-methyl-7-oxo -2,3-dihydro-7H-pyrido[3
, 2,1-1jl-1,3,4-benzoxadiazine-6-carboxylic acid was synthesized. It was recrystallized from a mixed solvent of chloroform and n-hexane. Melting point 229-233℃
(decomposition), MSm/z377 (M+),.

Example 39 9-Fluoro-3-methyl-7- obtained in Example 11
Oxo-10-(4-thiomorpholinyl)-2,3-dihydro-7H-pyrido[3,2,1-ijl-1,3,
4-benzoxocyanone-6-carboxylic acid (50 mg
) was suspended in dichloromethane (51), and 1fi
-Chloroperbenzoic acid (70% purity, 74 mg) was added. After stirring the mixture at room temperature for 18 hours, the solvent was distilled off under reduced pressure. The residue was washed with ether, dichloromethane, then a mixed solvent of chloroform and methanol, and recrystallized from dimethylformamide to give 1O-(1,1-dioxide-4-thiomorpholinyl)-9-fluoro-3-methyl-7-oxo. -2,3-nohydro7H-pyrido[3
, 2,1-1jl-1,3,4-benzoxadiazine-6-carboxylic acid (22-g) was obtained. Melting point〉300℃, M
Sm/z397 (M”).

Example 40 9-Fluoro-3-methyl-7-okyne-1O-(1-piveranonyl)-2,3-dihydro-7H-pyrido[3,2,1-1jl-113t.4 −
Benzoxanoanone-6-carboxylic acid (50+eg)
, chloroacetone (17 μl), triethylamine (4
A mixture of 0 μm) and dry trimethylformamide (1 ml) was heated at 80° C. for 3.5 hours. After distilling off the volatile substances under reduced pressure, the residue was suspended in water and the precipitate was collected by filtration. Recrystallization from a mixed solvent of dichloromecne and methanol gave 9-fluoro-3-methyl-7-oxo-10-[
4-(2-oxo-n-propyl)-1-piperazinyl]-2,3-nohydro7H-pyrido[3,2,1-i
jl-1,3,4-benzoxadiazine-6-carboxylic acid 32ml? I got it. Melting point 225-229°C (min%
), FAB-MSLa/z405(MH”).

The following compounds were synthesized in a similar manner to Example 40.

(dec,) 43 CH5Ct6CL 255~
257 ELOtl 391 (in Mtl) (
dec,) 44 FCHzClla 25
7～259 EtOll 395 (MH 10)
(dec,) 45 HO2CC112-256~259
1120 407 (M11+) (dec, ) 46 110=cc112 236
~238 He'll 389 (in Nil)
(dec, ) Example 48 - 9-fluoro-3-methyl-10 obtained in Seiichi Example 17
-[3-[(methylamino)methyl]-1-pyrrolidinyl]-7-oxo-2,3-7hydro-7H-pyrido[
10-[3-[(ethylmethyl7mi/)methyl] was prepared in the same manner as in Example 40 using 3,2,1-ijl-1,3,4-benzoxadiazine-6-carboxylic acid and ethyl ionod as raw materials. -1-pyrrolidinyl]-9-fluoro-3
-Methyl-7-oxo-2,3-dihydro-7H-pyrido[3,2,1-ijl-1,3,4-benzoxanoanone-6-carboxylic acid was obtained. It was recrystallized from a mixed solvent of chloroform, methanol and n-hexane.

Melting point: 210-225°C (No.)
l/Z4 0 5 (MH 10).

Example 49 10-4-3-carboxypropionyl-1-pibroiled 9-fluoro-3-methyl-7-oxo-10-<1-piperazinyl)-2,3-dihydro-7 obtained in Example 6
8-pyrido[3,2,1-ijl-1,3,4-benzoxadiazine-6-carboxylic acid (50 mg), anhydride 1 1! ! (21,6 mg), triethylamine (4
0 μm) and dry trimethylformamide (4te) was heated at 80° C. for 2 hours. The solvent was further removed under reduced pressure and the residue was suspended in water. The precipitate was collected by filtration and recrystallized from a mixture of dichloromethane and methanol to give 50a+H of 10-[4-(3-carboxypropionyl)-1-piperazinyl 1-9-fluoro-3
-Methyl-7-oxo-2,3-dihydro-78-pyrido[3,2,1-ijl-1,3,4-benzoxadiazine-6-carboxylic acid obtained 1mp, 257 259
°C (dec,): F A B-M Ss/z4 4 9
(MH+).

Example 50 10-(4-7cetyl-1-piperazinyl)-9-fluoro-3-methyl-7-oxo-2,3-dihydro-7
I(-pyrido[3,2,1-ijl-1-3t4-benzoxanoanone-6-carboxylic acid was prepared in the same manner as in Example 49, and 9-fluoro-3-methyl-7 obtained in Example 6
-oxo-10-(1-piperazinyl)-2,3-dihydro-71-1-pyrido[3,2,1-ijl-1,:
(s-mp, synthesized from ,4-benzoxacyanone-6-carboxylic acid and acetic anhydride and recrystallized from dichloromethane/methanol as a crystalline powder, 294-
296°C (dce, ); FAB MSm/z391 (
M)I”).

Example 51 Draw 7 Summer (-pyrid 3.2.1-i'4 3.4-
Synthesis Example 6 of benzoxadiazine-6-carvone
One chloro-3-methyl-7-okine-1O-(
1-piperazinyl)-2,3-nohydro-7H-pyrido[3,2,1-1jl-153s4-benzoxacyanone-6-carboxylic acid (30+g), methyl vinyl ketone (36μm) and ethanol (1,wl) The mixture was refluxed for 12 hours and then cooled to room temperature.

The precipitate was collected by filtration and crystallized from ethanol to give 28 mg of 9-fluoro-3-methyl-
7-oxo-10-[4-(3-oxo-n-butyl)
-1-piperazinyl]-2,3-dihydro-7H-pyrido[3,2,1-i,jl-1,3,4-benzoxanoanone-6-carboxylic acid was obtained. mp, 187-1
89'C (dec, ); FAB MSm/z419 (
Ml-1”).

Example 52 Nzooxadianone-6-carboxylic acid disodium salt!
1 wound 35% formalin (26 mg) and sodium hydrogen sulfate (
32 mg) and water (0,5111) were mixed, heated at 75°C for 30 minutes, and then cooled to room temperature.

9-fluoro-3-methyl-7-oxo-10-(1-piperazinyl)-2t3 obtained in Example 6 was added to this solution.
-dihydro-7H-pyrido[3,2,1-IJI-11
JI4-benzoxadiazine-6-carvone PIl (
io.

mg) and sodium hydroxide (15ωg) were added. After heating this solution at 75°C for 1 hour, ethanol (2xi)
was added and cooled to room temperature. The separated precipitate was collected by filtration, re-crystallized with water/ethanol (1:2), and
-Fluoro-3-methyl-7-oxo-10-[4-(
sulfonate methyl)-1-piveranonyl]-2+3-
Kuhydro 7 H-pyrido (3,2,1-ijl-1,
314-benzoxanoanone-6-carboxylic acid 2s1
Lium salt was obtained. Melting point 260-263°C (dec,);
IHNMR (D20) δ: 2.98 (3H1S), 3°05<48. m), 3.39 (4H, m), 3.84 (
2H, 9), 5.18 (2H1S), 7.55 (IH1
clec, )1,1=13.4Hz), 8.34(IH
lS).

Example 53 9-fluoro-3-methyl-10-[ obtained in Example 47
4-(4-nitrobenol)-1-piperazinyl]-7
-oxo-2,3-dihydro-7H-pyrido[3,2,
1-ijl-1y3,4-benzoxanoazine-6-
The carboxylic acid (100 IIIg) was hydrogenated in dichloromethane/methanol (1:1) SU under 5% P d/C (palladium on charcoal) catalyst.

After removing the catalyst by filtration, the filtrate was concentrated to dryness under reduced pressure.

The residue was recrystallized from ethanol to give 10-[4-
(4-7mi/benzyl)-1-piperazinyl 1-9-fluoro-3-methyl-7-oxo-2!3-dihydro-
7H-pyrido[3,2,1-1j1-1 *3-4-benzoxacyacune-6-carboxylic acid was obtained. Enemy front 23
7-238°C (dec,); F A B-WiSva/
y, 454 (Ml-1+).

Example 54 10-[3-(acetylaminomethyl)-1-pyrrolidinyl 1-9-fluoro-3-methyl-7-oxo-2,3-nohydro-78-pyrido (3,
2゜1-1jl-I l3t4-Benzoxadiazine-6-carboxylic acid (40 mg) and IN sodium hydroxide (2,5z1) were heated at 100°C for 3 hours. After cooling to room temperature, the reaction was neutralized with acetic acid. The separated precipitate was collected by filtration and recrystallized from methanol to obtain 10-[3-(amino/〆1,000)k)-1-pyrrolidinyl J of 15B.
-9-fluoro-3-methyl-7-oxo-2,3-dihydro-7H-bi! J)'I3,2.1-1jll
13.4-Benzoxanoacine-6-carboxylic acid was obtained. Melting point 177-180°C (dec,); FAB-MS
+o/z363 (in MFI).

Example 55 6,7-difluoro-8-hydroxy-1-(methylamino)-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid (50 ng) obtained in Reference Example (i) was mixed with tl? ,
Dissolve in dry trimethylformamide (2z1) and stir 9
Carbonylneumidazole (32 mg) was added. After stirring at room temperature for 2 hours, the mixture was heated at 80° C. for 5 hours.

The solvent was removed under reduced pressure and the residue was suspended in water and adjusted to pH 5 with acetic acid.
It was adjusted to The precipitate was separated by filtration and washed with methanol to give 35 II g of 6-fluoro-
8-Hydroxy-7-(1-imidazolyl)-1-(methyl-amino)-4-oxo-1,4-dihydro3-
Quinolinecarboxylic acid was obtained. E'AB-MSm/y, 3
19 (MH→);'H-N MR spectrum (d
, -D M2O) δ: 2.82 (3H1S), 4.1.
0(11-L d.

J=10.7Hz), 7.61 (I H, d), 7.
75 (IH% d), 8, 6 2 (IH
, s), 8.92 (IH, S), 15.33 (I
H, br, s).

Example 56 6-fluoro-8-hydroxy-7- obtained in Example 55
(1-imidazolyl)-1L(methyl-amino)-4-
Oxo-1,4-dihydro-3-ki/phosphoruscarboxylic acid (
15-g) was suspended in a mixture of 35% holemarin (1 ml) and nooxane (1i+1), and 1
Heated at 100-110°C for 5 hours. The solvent was removed under reduced pressure and the crystalline residue was washed with methanol to give 15 mg
pale pink powder 9-fluoro-10-(1imidazolyl)-3-methyl-7-oxo-2,3-dihydro-
The analytical sample from which 7H-pyrido13.2.1-ijl-1,3,4-benzoxacyanone-6-carboxylic acid was obtained was
It was prepared by recrystallization from a mixed solvent of dimethylformamide and ethanol. mp>300℃; FAB-MS~/
z3 3 1 (M H+).

9-fluoro-10-(1-imidazolyl)3-methyl-7-oxo-2,3-dihydro-7H-pyrido[3°2.1-ijl-1v: L4-benzoxadiazine-
Similarly to Example 5, 6-carboxylic acid was converted into 9-10-fluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido[3,2,1-
Also from iJl-1,3,4-benzoxacyanone-6-carboxylic acid and imidazole! ! It was done.

Example 57 9-fluoro-10-(3-hydroxy-1-pyrrolidinyl)-3-methyl-7-okyne-2 obtained in Example 21
．． 3-dihydro-7)-■-pyrido[3,2,1-ij
l-1=3.4-penzoxasoanone-6-carvone! (10 mg), anhydrous potassium carbonate (8+++ g) and trimethylformamide (0.5 ml) were mixed, stirred at room temperature for 1.5 hours, and then benzyl bromide (10,
8+++g) was added. The mixture was stirred at room temperature for 3 hours and the solvent was evaporated under reduced pressure.

The residue was suspended in water, extracted with chloroform, and the extract was concentrated to dryness under reduced pressure. The residue was treated with ether and 11
+*g of benzyl = 9-fluoro-10-(3-hydroxy-1-pyrrolidinyl)3-methyl-7-oxo-2
,3-nohydro7H-pyrido[3,2,1-ijl-
L3t4-benzoxadiazine-6-carborate was obtained. +ep, 196 198°C (dec, ): F
A B-MSm/z440 (MH”).

Example 58 Pennol 9-fluoro-10-(3-
Hydroxy-1-pyrrolidinyl)-3-methyl-7-oxo-2,3-dihydro-7H-pyrido[3,2,1-
iJl-1,3,4-benzoxacyanone-6-carboxylar) (8+ag) was dissolved in 0.2 xi of thionyl chloride and stirred at 60°C for 15 minutes. The reaction mixture was diluted with water and extracted with chloroform.

The extract was concentrated under reduced pressure and the residue was purified on silica gel (2
g) Chromatography and elution with chloroform yielded 2.8 g of benol 10-(3-chloro-1-
pyrrolidinyl) 9-fluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido [3,2°1-iJ
l-1v3*4-benzoxadiazine-6-carboxy sheet was obtained. Melting point>300°C; FAB-MSa+/
z4 5 8 (MH+), 4 4 6 0 (MH+
2) Master.

Example 59 Pencil obtained in Example 58 1O-(3-chloro-1-pyrrolidinyl)-9-fluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido[3,2,1- 1i
1-1.3.4-benzoxadiazine-6-carboxy sheet (2,5B) in chloroform with 5% Pd/
Hydrogenation was carried out under C catalyst.

After removing the catalyst by filtration, the filtrate was concentrated to dryness under reduced pressure.

The residue was recrystallized from ethanol and 1.01°C g of 1
O-(3-chloro-1- and lolinonyl)-9-fluoro-3-methyl-7-oxo-2,3-dihydro-78-
Pyrido[3,2,1-ijl-1*3,4-benzoxanoanone-6-carboxylic acid was obtained. Melting point 269-27
2°C (dec,); F A B-MSm/z3
6 8 (MH”), 3To (MH+2)
+.

Example 60 9-fluoro-3-methyl-10-(4-methyl-1-piperazinyl)-7- via fluoroborane intermediate
Oxo-2,3-hydro-7H-pyrido[3,2,1
-iJl-1y3y4-Benzoxadiazine-6-carbolambda acid synthesis method a) 9,10-7 fluoro-3-methyl-7-oxo-2,3-dihydro-78-bilyy13 obtained in Example 1゜2.1-ijl-1,3,4~penzoxanoanone-
A mixture of 6-carboxylic acid (1001011) and a 60% aqueous solution of borohydrocranic acid (lzl) was heated at 90° C. for 12 hours. After cooling the reaction mixture to room temperature, the precipitate was collected by filtration, washed with methanol and concentrated to dryness under reduced pressure, yielding 110 mg of crude! 3,10-difluoro-6-1-nofluoroboryl)oxy1-carbonyl1-3-methyl-2,3-dihydro-7H-pyrido[3
, 2, 1-1jll, 3,4-benzoxanoacin-7-one was obtained: FAB MSw/z331 (MH
”).

b) (Dissolving the above borane intermediate (33 mg) in dimethyl sulfoxide (1 mN) and stirring) N-
Methylbiveranone (15 μm) and triethylamine (2
0 μm) was added. After stirring for 3 hours at room temperature, the reaction mixture was lyophilized. The residue was crystallized from methanol.
8 mg of yellow crystals 6-[1(difluoroboryl)oxy-1carbonyl]-9-fluoro-3-methyl-10-(
4-methyl-1-piperazinyl)-2,3-dihydro,
-7H-pyrido[3,2,1-ijl-1,3,4-benzoxadiazin-7-one was obtained. Melting point 228-2
30°C (dec,): FAB-MSm/z411 (M
H1).

c) ) Ethylamine (3 μl) was added to a solution of the above borane intermediate (5+sg) in 95% ethanol (lxffi>). After heating to reflux for 4 hours, the reaction solution was cooled to room temperature. The resulting precipitate was filtered. 9-fluoro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-2,3-dihydro-7H-pyrido[3,2,1-ijl-1,3, 4-Benzoxanoanone-6-carboxylic acid was obtained. Melting point 268-269°C (
dec, ).

Example 61 9-fluoro-3- via acetoxyborane intermediate
Methyl-10-(4-methyl-1-piperazinyl)-7
-oxo-2,3-dihydro-7H-pyrido[3,2,
1-iJ coco-,3,4-benzoxadiazine-6-
Synthesis method of carboxylic acid a) 9,10-difluoro-3-methyl-7-oxo-2,3-dihydro- obtained in Example 1
7H-pyrido I,'3,2,1. -i, J] -1, 3,
4-Benzoxadiazine-6-carboxylic acid (100+
u) and acetic anhydride (1, mj and triacetoxyborane <
1- Mix 100 mf/) and heat at 140°C for 15 minutes. The reaction mixture was evaporated under reduced pressure. The residue was treated with acetone, filtered and 138 mg of 6-
[[(diacetoxyboryl)oxy1carbonyl]-
9,1,0-difluoro-3-methyl-2,3-dihy 1
z loaf 1(-pyrido[3,2゜1-ijl-1,3
,4-benzoxadiazin-7-one was obtained; FA
B-MS n1/Z 411 (MH″″).

b) N-methylpiperazine (15 μm) and triethylamine (20 μl) were added to a solution of the above borane intermediate (41 mg) in dimethyl sulfoxide (1rrB). After stirring the mixture for 2 hours at room temperature, the reaction mixture was lyophilized and the residue was crystallized from methanol/ethanol to give 34 mg of yellow crystals 6-1':[(diacetoxyboryl)oxy] carbonyl]-9-fluoro-3
-Methyl-10-(4-methyl-1-piperazinyl)-
2゜3-dihydro-7H-pyrido[3,2,1-i,j
l-1,3,4-benzoxadiazin-7-one was obtained. ; Melting point 156-157°C (dec, ); FA
B-MS m/z 49 L (M) [”).

C) The above borane intermediate (5 mg) was mixed with acetone (0°1 m
1) and added concentrated hydrochloric acid (2.5 μm). The reaction mixture was stirred at room temperature for 30 minutes and cooled in water. The resulting precipitate was collected by filtration and mixed with 95% ethanol (0.1 m
It was dissolved in water. Add triethylamine (2 μm) to this solution.
was added and the mixture was heated to reflux for 1 hour. After cooling the solution at room temperature, the raw precipitate was filtered 1. Collect them,
9-Fluoro-u-methyl-1(')-(4-methyl-
1-piperazinyl)-7-oxo-2,3-dihydro-
7H-pyrido[3,2,1-jjl-1,3,4-benzoxadiazine-6-carboxylic acid was obtained.

Melting point: 268-269°C (dec).

Example 02 Pivaloyloxymethyl=10-[3-(penzyloxyluponi!reamino)-1-pyrrolidinyl]-9-
Fluoro-3-methyl-7-oxo-2°3-dihydro-7H-pyrido E3,2. ]-LJI-1,3,4-Benzoki-11diazine-()-carboxilade Synthesis Example 29 10-[3-(benzyloxycarbonylamino)-1-pyrrolidinyl 1-9-fluoro-
3-Methyl-7-oxo-2,3-dihydro-7H-pyrido r3.2.1. - i J ]-1',3,4-benzoxadiazine-6-carboxylic acid (290 m#>, pivaloyloxymethyl chloride (130 μl), anhydrous potassium carbonate (1,66 mg) and dry dimethylpolamide (10 mj of the mixture was stirred for 8 hours at 45°C. The solvent was distilled off under reduced pressure and the residual liquid was dissolved in dichloromethane. The dichloromethane solution was washed with water and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure. The residue was recrystallized from ethyl acetate to give 325 mFI pivaloyloxymethyl 1.0-[3-(benzyloxycarbonylamino)-1-pyrrolidinyl 1-9-fluoro-3-methyl-oxo- 2゜3-dihydro-7H-pyrido [3,
2, 1-i, i 1-1. ．． 3.4-benzoxadiazine-6-carboxilade was obtained; melting point 185-18
8℃; FAB-MS m/z 597 (MH”
).

Example 63 pivaloyloxymethyl-], 0-(3-amino-1-
pyrrolidinyl)-9-fluoro-3-methyl-°7-oxo2,3-dihydro7H-pyrido[3,2,1-
Synthesis of Lj coco-,,3,4-benzoxadiazine-6-carborate pivaloyloxymethyl 1.0-(3-amino-1
-pyrrolidinyl)-9-2fluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido[3,2,1-
jjl-1,,3,4-benzoxadiazine-6-carboxylade was obtained in L7 in the same manner as in Example 30, and pivaloyloxymethyl 10-[3-(benzyloxycarbonyl) obtained in Example 62 was obtained. amino)-1-dilorinyl 1
-9-Fluoro-3-methyl-°/-oxo2,3-
dihydro-7H-pyrido[3,2,1-jjl-1゜3.4-benzoxadiazine-6-carboxylarh
(2C') Omg) and diluted with ethyl acetate and 11
Q' was precipitated from a warm mixture of -hexane and obtained as a pale brown powder.

'HNMR (CDCI,) δ: 1.22 (
9H, S), 1.6-2.4 (2H+, rn)
, 2.99 (3H, s), 3.3-4. 0 (5
H, m>, 4.98 (2H, s), 5.96 (2
1-r, s), '7. 6 4 (l t
[,d,,J-=14.4tIZ), 8.
3'/(I H, s); FAR-MS m/
y.

46-3 (MH”).

Example 64 Ethyl = 10-[3-(benzyloxycarbonylamino)-1-pyrrolidinyl]-9-fluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido f:3
,2.1-i,j]-1,3,4-benzoxadiazine-6-carboxylade 1,0-[3-(benzyloxyca!) obtained in Example 29
refonylamino)-1-pyrrolidinyl]-9-fluoro-3-methyl-7-oxo-2,3-dihydrof H
-pyridol), 2.1-jjl-1,3,4-benzoquinacyazine-6-carboxylic acid (337 nB),
Ethyl iodide (847zI) and anhydrous potassium carbonate (19
A mixture of 3rng) and dry dimethylformamide (12mN) was stirred at 45°C for 6 hours. The solvent was removed under reduced pressure and the residue was dissolved in dichloromethane. The dichloromethane solution was washed with water, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was applied to a silica gel column and eluted with a mixture of chloroform and acetone (20:1).
Collect purified fractions and dry under reduced pressure. The residue was recrystallized from ethyl acetate to give 271 mFI of ethyl = '1. Of
:3-(benzyloxycarbonylamino)-1-pyrrolidinyl-9-fluoro-3-methyl-7-oxo-
2,3-dihydro-71-1-pyrido[3,2,1-i
, 1l-1,3°4-penzoxadiazine-6-carboxybuto is obtained. Melting point 204-207℃; FAB
-MSm/z51t (MH+).

Example 65 Synthesis of ethyl-1t1)-(3-amino-1-pyroxasdinyl)-9-nororo-3-methyl-l-oxo-carboxylade Ethyl 10-[3-( Benzyloxycarbonylamino-9-fluoro-3-methyl-7-oxo-2.

3-dihydro-7H-pyrido[3,2.1-i,jl-
1,3.4-benzoxadiazine-6-carboxylade (200 mg) was added to chloroform (25 mg).
) and methanol (1-Omj) in a mixed solvent of 5% Pd
Hydrogenation was performed under a /c (120 my) catalyst for 23 hours.

After removing the catalyst by filtration, the filtrate was concentrated under reduced pressure.

Apply the residue to a silica gel column and elute with a mixed solvent of chloroform and methanol (4:1). The purified fractions were collected and concentrated to dryness under reduced pressure. The residue is further collected using T.
I, C (silica gel; chloroporm/methanol 3:1
); recrystallized from ethanol to give 71 mg of ethyl 1.0-<3-amino-1-pyrrolidinyl)-9-
Fluoro-3-methyl-'l-oxo2,3-dihydro-7 f(-pyrido r3,2.1-tjl -1,3
．． 4-benzoxadiazine-6-carboxilade was obtained. Melting point 187-192°C (dec.)
; FAB-MS m/Z 3 7 7 (M
H+).

Example 6 1 0- (3-Amino-1- and μ-lysinyl)-9-
Fluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido[3.2.1-i,jl-1,3.4
Synthesis of benzodiazine-6-carboxylic hydrochloride
,3-dihydro-7-pyrido[3,2.

1-i N-1.3.4-benzoxadiazine-()
A solution of -carboxylic acid (20 mg) in 1 ml of water was adjusted to 1 with 6N4 acid.The clear solution was lyophilized and the residue was dissolved in water/ethanol (1).
．． +2) to give 19 mg of 10-('3-amino-1-pyrrolidinyl)-9-fluoro-d-methyl-
'/norxone, 3-dihydro f14-pyrid 13.2.1-ijl-1. 3.4-penzoxadiazine-6-carboxylic acid acid deficiency. Don't get it, @ point 226~
228°C (dec.) Example 07 9-fluoro-3-methyl-10-(4-methyl-1-
piperazinyl)-7-oxo-2,3-dihydro-7H
-pyrido[3.2,]-ijl-1.

Synthesis of 3,4-benzoxadiazine-6-carboxylic hydrochloride In the same manner as in Example 66, 9-fluoro-3-methyl-
1.0-(4-Methyl-1-piperazinyl)-7-oxo-2.3-dihydro-7H-pyrido [3,2,1. −
i. jl-1,3.4-benzoxadiazine-6-carboxylic hydrochloride was obtained, melting point 264-266
℃ (dec.) Example 68 9-Fluoro-3-methyl-10-molpolyno-7-oxo-2,3-dihydro-°71]-pyrido(3,2,
]-]i,jl-1 9 obtained in Synthesis Example 9 of 3,4-penzooxypdiazine-carboxylic acid thorium salt
-Fluoro-3-methyl-10-mojreforino-7-oxo2,3-dihydro-7H-pyrido[3,2,]-
i. il-1. 3.

4-benzoxadiazine-〇-carvone (14 mg
) was suspended in water (10.4 ml), and IN-strium hydroxide (40 μl.) was added with stirring. The clear solution was lyophilized and the residue was dissolved in water/ethanol<1. :4)
crystallized from 1.2rrB&)9-fluoro-3-methyl-10-mojreporino7-oxo2.3-dihydro-7H-pyrido[3゜2.1-iJl-1,3,4
-obtain benzoxadiazine-6-carboxylic acid sodium salt. Melting point>300°C Example 69 9-nor]rho-(2-fluoroethyl)-10-
(4-methyl-1-piperazinyl)-'7-oxo2
,3-dihydro7H-pyrido[3゜2.1-i,jl
-Ethyl-8-benzyloxy- obtained in Synthesis Reference Example (r) of -1,3,4-benzoxadiazine-6-carboxylic acid
6, ゛l-difluoro]-(formylamino)-4-
Reference examples using oxo-1,4-dihydro-3-quinolinecarboxilade as a starting material <g, h and i) (using 1-noromo-2-fluoroethane in place of methyl iodide), Example 1 and Examples According to the series of methods in 5, 9
-Fluoro-3-(2-fluoroethyl')-10-(
4-Methyl-1-piperazinyl)-7-oxo-2゜3
-dihydro-7[(-pyrido r3.2.1-ijl-1
, 3,4-benzoxadiazine-6-carboxylic acid was prepared and recrystallized from methanol to obtain a crystalline powder. Melting point 220-224℃, MSm/z 394 (M
”) Examples 70-77 The following compounds were obtained from the compound obtained in Example 1 using a method similar to either Example 5 or Example 29/3 (1).

The following compounds were also obtained from the compound obtained in Example 1 using methods similar to either those described in Example 5 or Examples 29/30.

10- [3-(Aminomethyl)-4-methyl-1=pyrrolidinyl, 1-9-fluoro-3-methyl-'7-oxo 2,3-dihydro 7H-pyrido 13.2. J-
ijl-1,3,4-benzooxydiazine-76-carpoic acid, 1o-[3-r(ethylamino)methyl]-4-methyl-1-pyrrolidinyl 1-9-fluoro-3-methyl- 7
-oxo-2,3-dihydro-'/B-pyrido 13.2
．． I-i, i l-1,3,4-benzoxadiazine-6-carboxylic acid, 1.0-[3-(aminomethyl)-
4-chloro0-1-pyrrolidinyl]-9-fluoro-3-
Methyl-7-oxo-2,3-dihydro-7H-pyrido 13.2.1-1. jl-1,3,4-benzoxadiazine-6-carboxylic acid, 10-13- (aminomethyl)-4-fluoro-1-
pyrrolidinyl 1-9-fluoro-3-methyl-'/-oxo2,3-dihydro-7tT-pyrido[3,2,1
-ijl-1,3,4-benzoxadiazine-6-carboxylic acid, 10- [3-chloro-4-[(methylamino)methyl 1-1-pyrrolidinyl]-9-fluoro-3-methyl-
°7-oxo2.3-dihydro 7H-bili FL3,
2.1-i,j l-1,,3,4-benzoxadiazine-6-carboxylic acid, 9-fluoro-1,0-[3-
Fluoro-4[(methylamine)methyl]-1-pyrrolidinyl]-3-menal-7-oxo2.3-dihydro-'7H-pyrido 13.2. l-i, jl-1,3
, 4-benzoxadiazine-6-carboxylic acid, 10-
[3-chloro-4-[(ethylamine)methyl 1-1
-pyrrolidinyl 1-9-fluoro-3-methyl-f-oxo-2,3-dihydro-7H-dilide I3,2,1.
-iJ J-1,3,4-benzoxadiazine-6-
Calebonic acid, 10-[3-['(ethylamino)methyl 14-fluoro-1-pyrrolidinyl]-9-fluoro-3-menal-7-oxo 2,3-dihydro-7H-
Virido r3,2.1-i, jl-1,3,4-benzoxadiazine-6-carboxylic acid, 1o-(3-amino-
4-Methoxy-]-pyrrolidinyl>-9-fluoro-3
-Methyl-7-oxo-2,3-dihydro-7H-pyrido[3,2°1-t, J l-1,'3.4-benzoxadiazine-6-carboxylic acid, 9-fluoro-1 ,0-[3-methoxy-4(methylamino)-1-pyrrolidinyl]-3-methyl-l-oxo-2,3-dihydro-7H-pyrido 13.2,1. −
i, j l-1,3,4-benzoxadiazine-6-
Carboxylic acid, 1,0-[3-(ethylamino)-4-methoxyto-1-pyrrolidinyl]-9-fluoro-3-methyl-7
-oxo-2,3-dihydro-7F, [-pyrido13,
2,1-ji l-'I, 3.4-benzoxadiazine-〇-carboxylic acid, 9-fluoro-10-(3-hydroxy-4-methoxytolu-7-oxo-2.3-dihydro-7H -pyrido[3,2
, '1-ijl-1. 3.4-Benzoxadiazine-6-carboxylic acid, 10-(3-amino-4-chloro-1-pyrrolidinyl)
-9-Fluoro-3-methyl-7-oxo-2.3-dihydro-7H-pyrido[3,2.1-ij l-1.3
．． 4-Benzoxadiazine-6-carboxylic acid, 10-(3-amino-4-fluoro-pyrrolidinyl)-
9-Fluoro-3-methyl-7-oxo-z. 3-dihydro T'] - '/' l-] -pyrido f3.2.1
-L. j i-1.3.4--benzoxadiazine-
・〇-carboxylic acid, 10-[3-chloro-4-(methylamino)-1-pyrrolidinyl 1-9-fluoro-3-methyl-7-oxo-
2.3-dihydro-7H-pyrido 13,2,L-4,j
l-1. 3.4-Benzoxadiazine-6-carboxylic acid, 9-fluoro-1.0-[3-fluoro-4-(methylamino)-1-pyrrolidinyl]-3-methyl-7-oxo-2,3 -dihydro-'71(-pyrido r3,2.1
-ijl-1,3,4-benzoxadiazine-6-carboxylic acid, 9-fluoro-3-methyl-10-(1-oxide-4
-thiomorpholinyl)-7-oxo-2゜3-dihydro-'7H-pyrido[3,2,1-i-il-1,,3
, 4-penzoxadiazine-6-carboxylic acid, 9-fluoro-10-1"1-hydroxy-4-(methylamino)-1-pyrrolidinyl]-3-methyl-゛7-
Oxo-2,3-dihydro-7H-pyrido[3,2,I
-j,,j l-1,3,4-benzoxadiazine-
6-carboxylic acid, Example 78 10-r3-[(4-aminobenzyl)aminoco-
1-pyrrolidinyl l-1-9-fluoro-3-methyl-
゛? -oxo2.3-dihydro°7H-pyrido[3
,2,1-Lj',l-1,,Synthesis of 3,4-benzoxadiazine-6-carboxylic acid 10-1-3-1: (
4-aminobenzyl)amine 1-1-pyrrolidinyl]-
9-Fluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido[3,2,1,-t,jl-t+
3.4-Benzoxadiazine-6-carboxylic acid is the 1,0-(3-amino-1-pyrrolidinyl)-9-fluoro-u-methyl-? -Oxo2,
3-dihydro'71-1-pyrido 13.2, 1. −
i, j 1-1.3.4-benzoxadiazine-
Examples 47 and 53 using ()-carboxylic acid as a starting material
It was obtained in the same manner as described above. Melting point 180-182℃
(dec,), FAB-MS m/z 453 (M[
-i+).

Actual hk example 79 9-Fluoro-10-[3-[[(dimethylamino)methylene]-amino]-1-pyrrolidinyl] = 3-methyl-l-oxo2,3-dihydro-7H-pyridori
2. +-L,j I-1,3,4=1,0-3-amino-1-pyrrolidinyl)-9-fluoro obtained in Synthesis of benzoxadiazine-(゛)-carboxylic acid JiiK Example 30 -3-methyl-7-oxo-2,3-dihydro-
7H-pyrido [3°2.1. -L, J I-1,'3.
4--benzoxadiazine-6-carboxylic acid (14m
FI) and N,N-dimethylformamide dimethyl acetal (6711) were dried in DMF (0,5rr+1>
Suspend in water and stir at room temperature for 8.5 hours. The precipitate was collected by filtration, washed with dimethylformamide and ether, and then recrystallized from dimethylformamide to give 8mfI of 9-fluoro-10-[3-[[(dimethylamino>methylene]amino]-1-pyrrolidinyl]-3- Methyl-
7-oxo-2,3-dihydro-7H-pyrido l”C2
,,l-1j l-1,3,4-benzoki.1rdiazine-6-carboxylic acid was obtained as pale gray crystals. Melting point 2
1 8--22. <') ℃ (dec,) , F
'At u-MS m/z 4 04 (MH 10).

Example 80 9-fluoro-3-methyl-10-(4-methyl-1-
piperazinyl)-'7-oxo2,3-dihydro-7
Synthesis of 1(~pyrido[3,2,1-5j]-1゜3.4-penzoxadiazine-6-carboxylic acid sodium salt 9-fluoro-3-methyl-10-(4-methyl-1 −
piperazinyl)-7-oxo-2,3-dihydro-7H
-pyrido[3,2,1-ijl -1,3,4-benzoxadiazine-6-carboxylic acid (520my) at 0.
Dissolved in 5N sodium hydroxide (2.88ml). The clear solution was evaporated to 555mg
A pale yellow powder was obtained which was recrystallized from ethanol to give 9-fluoro-3-methifle-10-(4-methyl-1-beverazinur)-7-oxo-2,3-dihydro-7H-pyrido I3,2, 1. -i, i l-1,3,4-benzoxadiazine-6-carboxylic acid sodium salt obtained 7
The sample was further dried at 80° C. for 2 F1 to obtain a sample for obtaining physical properties. Melting point 252-254°C (dec, ), F'AB-
MS m/z 385.

The following examples demonstrate pharmaceutical compositions containing compounds provided by the present invention.

Example A Interlocking (in
t, erlocking) gelatin capsules were prepared by conventional methods;
2,1ijl-1,:(,4-benzoxadiazine-
6-carboxylic acid 2 (10+syl bis:nol (r-, uviskol) 20 I
Ilg (Water-soluble polyvinylpyrrolidone) Mannitol 20+*fI Talc 151 Magnesium suderate l\-2'' -257g Example [3 Tablets each containing the following ingredients were prepared by a conventional method. ; 9-Fluoro-tomethyl-1()-(4-methyl-1-piperazinyl) ゛ll-上-2. Todihydro 71-1 pyrido [:l
,2,1ijl-1,3,4-benzoxadiazine-
6-carboxylic acid 200+ng starch
4.4B Carpoximena! Recellulose Calcium 301 Crystalline Cellulose 40 Octopus V Magnesium Stearate 6m920mg

Claims (1)

[Claims] 1) General formula (I) ▲ Numerical formulas, chemical formulas, tables, etc. ▼ In the formula, R^1 represents a hydrogen atom or a carboxy protecting group; R^2 represents a hydrogen atom or a halogen atom Indicates a lower alkyl group which may be substituted with; R^3 and R^4
each independently represents a hydrogen atom or a lower alkyl group which may be substituted with a hydroxyl group or a substituted or unsubstituted amino group; X represents a halogen atom; and R^5 and R^6 are Each independently represents a hydrogen atom, or a lower alkyl group optionally substituted with a hydroxyl group, a lower alkoxy group, or a substituted or unsubstituted amino group; or R^5 and R^6 together with the adjacent nitrogen atom may form a 5- to 7-membered heterocycle, and the heterocycle may be substituted with one or more substituents on its carbon atoms, and the heterocycle may be substituted with -NR
^7-, -O-, -S-, -SO-, -SO_2- or -NR^7-CO- [where R^7 is a hydrogen atom, a lower alkenyl group, an optionally substituted lower Alkyl group or aralkyl group, or general formula (II) -(CH_2)nCOR^8(II) (wherein, n is 1 to 4, and R^8 is a hydrogen atom, a lower alkoxy group, or a substituted and pharmaceutically acceptable salts thereof, and compounds of formula (I) and their Hydrates or solvates of salts. 2), when R^3 and/or R^4 are a substituted amino-lower alkyl group, a di-lower alkylamino-lower alkyl group, a lower alkylamino-lower alkyl group, or a lower cycloalkyl-amino-lower The compound according to claim 1, which is an alkyl group. 3) When R^5 and/or R^6 are a substituted amino-lower alkyl group, a di-lower alkylamino-lower alkyl group, a lower alkylamino-lower alkyl group, or a lower cycloalkylamino-lower alkyl group. The compound according to claim 1 or 2, which is a group. 4), R^5 and R^ when they form a 5- to 7-membered heterocycle together with adjacent nitrogen atoms, and the carbon atoms of the heterocycle are substituted with one or more substituents. 6 is a hydroxyl group, a lower alkoxy group, an amino group, a lower alkylamino group, a lower cycloalkylamino group, a di-lower alkylamino group, a lower alkanoylamino group, a benzyloxycarbonylamino group, a halogen atom, a lower alkyl group, an amino-lower Alkyl, lower alkylamino-lower alkyl group, lower cycloalkylamino-lower alkyl group, di-lower alkylamino-lower alkyl group, lower alkanoylamino-lower alkyl group, hydroxy-
Claim 1 having a substituent selected from a lower alkyl group; a phenyl group (optionally substituted with an amino group, a halogen atom, a hydroxyl group and/or a lower alkoxy group) and a heterocycle on a carbon atom Or a compound according to item 2. 5), R^5 and R^ when they form a 5- to 7-membered heterocycle together with adjacent nitrogen atoms, and the carbon atoms of the heterocycle are substituted with one or more substituents; 6 is a benzylamino group optionally substituted with a nitro group, an amino group, a halogen atom, a hydroxyl group and/or a lower alkoxy group; or a general formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (In the formula, R^5^ 0 and R^5^1 are substituents selected from a lower alkyl group, or a group represented by a 5- to 8-membered saturated nitrogen-containing heterocycle together with a nitrogen atom. A compound according to item 1 or item 2. 6) When R^7 is a substituted lower alkyl group, R^7 is substituted with a hydroxyl group, a lower alkoxy group, an amino group, a lower alkylamino group, a di-lower alkylamino group, a halogen atom, a carboxy group and/or a sulfo group. The compound according to any one of claims 1 to 5, which is a lower alkyl group. 7) When R^7 is a substituted aralkyl group, it is substituted with one or more amino groups, nitro groups, lower alkylamino groups, di-lower alkylamino groups, halogen atoms and/or lower alkoxy groups. The compound according to any one of claims 1 to 5, which is an aralkyl group. 8) The compound according to claim 7, wherein the aralkyl group is a benzyl group optionally substituted with a group mentioned in claim 7. 9), a group of general formula (II) having an amino group substituted by a lower alkyl group and/or a lower cycloalkyl group when R^7 is a group of general formula (II) having a substituted amino group; A compound according to any one of claims 1 to 5. 10), general formula (I) having a substituted lower alkyl group
Claims 1 to 5 in which R^7 in the case of group I) is a group of general formula (II) having a lower alkyl group substituted with a carboxy group and/or a lower alkoxycarbonyl group. A compound according to any one of 11), in the case of a group of general formula (II) having a substituted aryl group, R^7 is substituted with one or more halogen atoms, lower alkoxy groups, hydroxyl groups, nitro groups and/or amino groups The compound according to any one of claims 1 to 5, which is a group of general formula (II) having an aryl group. 12) A compound according to claim 11, wherein the aryl group is a phenyl group optionally substituted with a group as defined in claim 11. 13), Claims 1 to 1 in which X is fluorine
A compound according to any one of Item 2. 14) The compound according to any one of claims 1 to 13, wherein R^1 is a hydrogen atom. 15) The compound according to any one of claims 1 to 14, wherein R^2 is a methyl group. 16) The compound according to any one of claims 1 to 15, wherein R^3 is a hydrogen atom. 17) The compound according to any one of claims 1 or 3 to 16, wherein R^4 is a hydrogen atom. 18), Claims 1, 2, and 4 in which the R^5R^6N- group is ▲There are mathematical formulas, chemical formulas, tables, etc.▼
The compound according to any one of Items 1 and 13 to 17. 19), Claims 1, 2, and 4 in which the R^5R^6N- group is ▲There are mathematical formulas, chemical formulas, tables, etc.▼
The compound according to any one of Items 1 and 13 to 17. 20), 9-fluoro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-2,3-dihydro-7H-pyrido[3,2,1-ij]-1,3, 4-
Claim 1 is a hydrate or solvate of benzoxadiazine-6-carboxylic acid or a pharmaceutically acceptable salt thereof, or a compound thereof or a salt thereof.
Compounds described in Section. 21), 9-fluoro-3-methyl-7-oxo-10
-(1-piperazinyl)-2,3-dihydro-7H-pyrido[3,2,1-ij]-1,3,4-benzoxadiazine-6-carboxylic acid or a pharmaceutically acceptable thereof The compound according to claim 1, which is a salt, or a hydrate or solvate of the compound or a salt thereof. 22), 9-fluoro-3-methyl-10-(3-methyl-1-piperazinyl)-7-oxo-2,3-dihydro-7H-pyrido[3,2,1-ij]-1,3, 4-
Claim 1 is a hydrate or solvate of benzoxadiazine-6-carboxylic acid or a pharmaceutically acceptable salt thereof, or a compound thereof or a salt thereof.
Compounds described in Section. 23), 9-fluoro-3-methyl-7-oxo-10
-(3-phenyl-1-piperazinyl)-2,3-dihydro-7H-pyrido[3,2,1-ij]-1,3,4
The compound according to claim 1, which is a hydrate or solvate of -benzoxadiazine-6-carboxylic acid or a pharmaceutically acceptable salt thereof, or a compound thereof or a salt thereof. 24), 9-fluoro-3-methyl-10-monopholino-7-oxo-2,3-dihydro-7H-pyrido [3,
2,1-ij]-1,3,4-benzoxadiazine-
The compound according to claim 1, which is a hydrate or solvate of 6-carboxylic acid or a pharmaceutically acceptable salt thereof, or a compound thereof or a salt thereof. 25), 9-fluoro-3-methyl-10-[3-[(
methylamino)methyl]-1-pyrrolidinyl]-7-oxo-2,3-dihydro-7H-pyrido[3,2,1-
ij]-1,3,4-benzoxadiazine-6-carboxylic acid or a pharmaceutically acceptable salt thereof, or a hydrate or solvate of a compound thereof or a salt thereof A compound according to item 1. 26), 10-[3-[(ethylamino)methyl]-1
-pyrrolidinyl]-9-fluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido[3,2,1-
ij]-1,3,4-benzoxadiazine-6-carboxylic acid or a pharmaceutically acceptable salt thereof, or a hydrate or solvate of a compound thereof or a salt thereof A compound according to item 1. 27), 10-(3-amino-1-pyrrolidinyl)-9
-Fluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido[3,2,1-ij]-1,3,4-
Claim 1 is a hydrate or solvate of benzoxadiazine-6-carboxylic acid or a pharmaceutically acceptable salt thereof, or a compound thereof or a salt thereof.
Compounds described in Section. 28), 9-fluoro-3-methyl-10-[3-[(
Methylamino)-1-pyrrolidinyl]-7-oxo-2
,3-dihydro-7H-pyrido[3,2,1-ij]-
Claim 1 is a hydrate or solvate of 1,3,4-benzoxadiazine-6-carboxylic acid or a pharmaceutically acceptable salt thereof, or a compound thereof or a salt thereof. Compounds described in. 29), 10-[3-(ethylamino)-1-pyrrolidinyl]-9-fluoro-3-methyl-7-oxo-2,
3-dihydro-7H-pyrido[3,2,1-ij]-1
, 3,4-benzoxadiazine-6-carboxylic acid or a pharmaceutically acceptable salt thereof, or a hydrate or solvate of a compound thereof or a salt thereof. Compounds described. 30), 10-(3,4-dimethyl-1-piperazinyl)-9-fluoro-3-methyl-7-oxo-2,3-
Dihydro-7H-pyrido[3,2,1-ij]-1,3
, 4-benzoxadiazine-6-carboxylic acid or a pharmaceutically acceptable salt thereof, or a hydrate or solvate of a compound thereof or a salt thereof. Compound. 31), 9-fluoro-10-(3-methoxy-1-pyrrolidinyl]-3-methyl-7-oxo-2,3-dihydro-7H-pyrido[3,2,1-ij]-1,3, 4
The compound according to claim 1, which is a hydrate or solvate of -benzoxadiazine-6-carboxylic acid or a pharmaceutically acceptable salt thereof, or a compound thereof or a salt thereof. 32), 9-fluoro-3-methyl-7-oxo-10
-[4-[(3-oxo-n-butyl)-1-piperazinyl]-2,3-dihydro-7H-pyrido[3,2,1
-ij]-1,3,4-benzoxadiazine-6-carboxylic acid or a pharmaceutically acceptable salt thereof, or a hydrate or solvate of a compound thereof or a salt thereof. A compound according to scope 1. 33), disodium = 9-fluoro-3-methyl-7
-oxo-10-[4(sulfonatomethyl)-1-piperazinyl]-2,3-dihydro-7H-pyrido[3,2
,1-ij]-1,3,4-benzoxadiazine-6
- The compound according to claim 1, which is a carboxylate or a hydrate or solvate thereof. 34), 10-[4-(aminobenzyl)-1-piperazinyl]-9-fluoro-3-methyl-7-oxo-2
,3-dihydro-7H-pyrido[3,2,1-ij]-
Claim 1 is a hydrate or solvate of 1,3,4-benzoxadiazine-6-carboxylic acid or a pharmaceutically acceptable salt thereof, or a compound thereof or a salt thereof. Compounds described in. 35), 10-[3-(aminomethyl)-1-pyrrolidinyl]-9-fluoro-3-methyl-7-oxo-2,
3-dihydro-7H-pyrido[3,2,1-ij]-1
, 3,4-benzoxadiazine-6-carboxylic acid or a pharmaceutically acceptable salt thereof, or a hydrate or solvate of a compound thereof or a salt thereof. Compounds described. 36), 9-fluoro-10-(1-imidazolyl)-
3-Methyl-7-oxo-2,3-dihydro-7H-pyrido[3,2,1-ij]-1,3,4-benzoxadiazine-6-carboxylic acid or its pharmaceutically acceptable The compound according to claim 1, which is a salt thereof, or a hydrate or solvate of a compound thereof or a salt thereof. 37), 10-(4-ethyl-1-piperazinyl]-9
-Fluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido[3,2,1-ij]-1,3,4-
Claim 1 is a hydrate or solvate of benzoxadiazine-6-carboxylic acid or a pharmaceutically acceptable salt thereof, or a compound thereof or a salt thereof.
Compounds described in Section. 38), 9-fluoro-10-[4-(2-hydroxyethyl)-1-piperazinyl]-3-methyl-7-oxo-2,3-dihydro-7H-pyrido[3,2,1-i
j]-1,3,4-benzoxadiazine-6-carboxylic acid or a pharmaceutically acceptable salt thereof, or a hydrate or solvate of a compound thereof or a salt thereof A compound according to item 1. 39), 9-fluoro-3-methyl-10-(4-methyl-1-imidazolyl)-7-oxo-2,3-dihydro-7H-pyrido[3,2,1-ij]-1,3, 4-
Claim 1 is a hydrate or solvate of benzoxadiazine-6-carboxylic acid or a pharmaceutically acceptable salt thereof, or a compound thereof or a salt thereof.
Compounds described in Section. 40), 9-Fluoro-3-methyl-10-[3-methyl-4-[(methylamino)methyl]-1-pyrrolidinyl]-7-oxo-2,3-dihydro-7H-pyrido[
3,2,1-ij]-1,3,4-benzoxadiazine-6-carboxylic acid or a pharmaceutically acceptable salt thereof, or a hydrate or solvate of the compound or a salt thereof The compound according to claim 1, which is 41), 10-[3-(aminomethyl)-4-methyl-
1-pyrrolidinyl]-9-fluoro-3-methyl-7-
Oxo-2,3-dihydro-7H-pyrido[3,2,1
-ij]-1,3,4-benzoxadiazine-6-carboxylic acid or a pharmaceutically acceptable salt thereof, or a hydrate or solvate of a compound thereof or a salt thereof. A compound according to scope 1. 42), 10-[3-[(ethylamino)methyl]-4
-methyl-1-pyrrolidinyl]-9-fluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido[
3,2,1-ij]-1,3,4-benzoxadiazine-6-carboxylic acid or a pharmaceutically acceptable salt thereof, or a hydrate or solvate of the compound or a salt thereof The compound according to claim 1, which is 43), 10-[3-(aminomethyl)-4-chloro-
1-pyrrolidinyl]-9-fluoro-3-methyl-7-
Oxo-2,3-dihydro-7H-pyrido[3,2,1
-ij]-1,3,4-benzoxadiazine-6-carboxylic acid or a pharmaceutically acceptable salt thereof, or a hydrate or solvate of a compound thereof or a salt thereof. A compound according to scope 1. 44), 10-[3-(aminomethyl)-4-fluoro-1-pyrrolidinyl]-9-fluoro-3-methyl-7
-oxo-2,3-dihydro-7H-pyrido[3,2,
1-ij]-1,3,4-benzoxadiazine-6-
The compound according to claim 1, which is a hydrate or solvate of a carboxylic acid or a pharmaceutically acceptable salt thereof, or a compound thereof or a salt thereof. 45), 10-[3-chloro-4-[(methylamino)
methyl]-1-pyrrolidinyl]-9-fluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido[
3,2,1-ij]-1,3,4-benzoxadiazine-6-carboxylic acid or a pharmaceutically acceptable salt thereof, or a hydrate or solvate of the compound or a salt thereof The compound according to claim 1, which is 46), 9-fluoro-10-[3-fluoro-4-[
(Methylamino)methyl]-1-pyrrolidinyl]-3-
Methyl-7-oxo-2,3-dihydro-7H-pyrido[3,2,1-ij]-1,3,4-benzoxadiazine-6-carboxylic acid or a pharmaceutically acceptable salt thereof , or a hydrate or solvate of the compound or a salt thereof. 47), 10-[3-chloro-4-[(ethylamino)
methyl]-1-pyrrolidinyl]-9-fluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido[
3,2,1-ij]-1,3,4-benzoxadiazine-6-carboxylic acid or a pharmaceutically acceptable salt thereof, or a hydrate or solvate of the compound or a salt thereof The compound according to claim 1, which is 48), 10-[3-[(ethylamino)methyl]-4
-fluoro-1-pyrrolidinyl]-9-fluoro-3-
Methyl-7-oxo-2,3-dihydro-7H-pyrido[3,2,1-ij]-1,3,4-benzoxadiazine-6-carboxylic acid or a pharmaceutically acceptable salt thereof , or a hydrate or solvate of the compound or a salt thereof. 49), 10-(3-amino-4-methoxy-1-pyrrolidinyl)-9-fluoro-3-methyl-7-oxo-
2,3-dihydro-7H-pyrido[3,2,1-ij]
-1,3,4-benzoxadiazine-6-carboxylic acid or a pharmaceutically acceptable salt thereof, or a hydrate or solvate of a compound thereof or a salt thereof Claim 1 Compounds described in Section. 50), 9-fluoro-10-[3-methoxy-4-(
Methylamino)-1-pyrrolidinyl]-3-methyl-7
-oxo-2,3-dihydro-7H-pyrido[3,2,
1-ij]-1,3,4-benzoxadiazine-6-
The compound according to claim 1, which is a hydrate or solvate of a carboxylic acid or a pharmaceutically acceptable salt thereof, or a compound thereof or a salt thereof. 51), 10-[3-(ethylamino)-4-methoxy-1-pyrrolidinyl]-9-fluoro-3-methyl-7
-oxo-2,3-dihydro-7H-pyrido[3,2,
1-ij]-1,3,4-benzoxadiazine-6-
The compound according to claim 1, which is a hydrate or solvate of a carboxylic acid or a pharmaceutically acceptable salt thereof, or a compound thereof or a salt thereof. 52), 9-fluoro-10-(3-hydroxy-4-
methoxy-1-pyrrolidinyl]-3-methyl-7-oxo-2,3-dihydro-7H-pyrido[3,2,1-i
j]-1,3,4-benzoxadiazine-6-carboxylic acid or a pharmaceutically acceptable salt thereof, or a hydrate or solvate of a compound thereof or a salt thereof A compound according to item 1. 53), 10-(3-amino-4-chloro-1-pyrrolidinyl)-9-fluoro-3-methyl-7-oxo-2
,3-dihydro-7H-pyrido[3,2,1-ij]-
Claim 1 is a hydrate or solvate of 1,3,4-benzoxadiazine-6-carboxylic acid or a pharmaceutically acceptable salt thereof, or a compound thereof or a salt thereof. Compounds described in. 54), 10-(3-amino-4-fluoro-1-pyrrolidinyl]-9-fluoro-3-methyl-7-oxo-
2,3-dihydro-7H-pyrido[3,2,1-ij]
-1,3,4-benzoxadiazine-6-carboxylic acid or a pharmaceutically acceptable salt thereof, or a hydrate or solvate of a compound thereof or a salt thereof Claim 1 Compounds described in Section. 55), 10-[3-chloro-4-(methylamino)-
1-pyrrolidinyl]-9-fluoro-3-methyl-7-
Oxo-2,3-dihydro-7H-pyrido[3,2,1
-ij]-1,3,4-benzoxadiazine-6-carboxylic acid or a pharmaceutically acceptable salt thereof, or a hydrate or solvate of a compound thereof or a salt thereof. A compound according to scope 1. 56), 9-fluoro-10-[3-fluoro-4-(
Methylamino)-1-pyrrolidinyl]-3-methyl-7
-oxo-2,3-dihydro-7H-pyrido[3,2,
1-ij]-1,3,4-benzoxadiazine-6-
The compound according to claim 1, which is a hydrate or solvate of a carboxylic acid or a pharmaceutically acceptable salt thereof, or a compound thereof or a salt thereof. 57), 10-[4-(aminomethyl)-1-piperidyl]-9-fluoro-3-methyl-7-oxo-2,3
-dihydro-7H-pyrido[3,2,1-ij]-1,
Claim 1 which is a hydrate or solvate of 3,4-benzoxadiazine-6-carboxylic acid or a pharmaceutically acceptable salt thereof, or a compound thereof or a salt thereof. compound. 58), 9-fluoro-10-(4-hydroxy-1-
piperidyl)-3-methyl-7-oxo-2,3-dihydro-7H-pyrido[3,2,1-ij]-1,3,4
The compound according to claim 1, which is a hydrate or solvate of -benzoxadiazine-6-carboxylic acid or a pharmaceutically acceptable salt thereof, or a compound thereof or a salt thereof. 59), 9-fluoro-3-methyl-7-oxo-10
-[4-(1-pyrrolyl)-1-piperidyl]-2,3
-dihydro-7H-pyrido[3,2,1-ij]-1,
Claim 1 which is a hydrate or solvate of 3,4-benzoxadiazine-6-carboxylic acid or a pharmaceutically acceptable salt thereof, or a compound thereof or a salt thereof. compound. 60), 9-fluoro-10-(1-homopiperazinyl)-3-methyl-7-oxo-2,3-dihydro-7H
-pyrido[3,2,1-ij]-1,3,4-benzoxadiazine-6-carboxylic acid or a pharmaceutically acceptable salt thereof, or a hydrate of the compound or a salt thereof; The compound according to claim 1, which is a solvate. 61), 9-fluoro-10-(3-hydroxy-1-
pyrrolidinyl)-3-methyl-7-oxo-2,3-dihydro-7H-pyrido[3,2,1-ij]-1,3,
The compound according to claim 1, which is a hydrate or solvate of 4-benzoxadiazine-6-carboxylic acid or a pharmaceutically acceptable salt thereof, or a compound thereof or a salt thereof. . 62), 9-fluoro-3-methyl-7-oxo-10
-(4-n-propyl-1-piperazinyl)-2,3-
Dihydro-7H-pyrido[3,2,1-ij]-1,3
, 4-benzoxadiazine-6-carboxylic acid or a pharmaceutically acceptable salt thereof, or a hydrate or solvate of a compound thereof or a salt thereof. Compound. 63), 9-fluoro-10-[4-(2-fluoroethyl)-1-piperazinyl]-3-methyl-7-oxo-2,3-dihydro-7H-pyrido[3,2,1-ij
]-1,3,4-benzoxadiazine-6-carboxylic acid or a pharmaceutically acceptable salt thereof, or a hydrate or solvate of a compound thereof or a salt thereof. Compound according to item 1. 64), 10-[4-(carboxymethyl)-1-piperazinyl]-9-fluoro-3-methyl-7-oxo-
2,3-dihydro-7H-pyrido[3,2,1-ij]
-1,3,4-benzoxadiazine-6-carboxylic acid or a pharmaceutically acceptable salt thereof, or a hydrate or solvate of a compound thereof or a salt thereof Claim 1 Compounds described in Section. 65), 10-(4-allyl-1-piperazinyl)-9
-Fluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido[3,2,1-ij]-1,3,4-
Claim 1 is a hydrate or solvate of benzoxadiazine-6-carboxylic acid or a pharmaceutically acceptable salt thereof, or a compound thereof or a salt thereof.
Compounds described in Section. 66), 10-(1,1-dioxide-4-thiomorpholinyl)-9-fluoro-3-methyl-7-oxo-2
,3-dihydro-7H-pyrido[3,2,1-ij]-
Claim 1 is a hydrate or solvate of 1,3,4-benzoxadiazine-6-carboxylic acid or a pharmaceutically acceptable salt thereof, or a compound thereof or a salt thereof. Compounds described in. 67), 9-fluoro-3-methyl-10-(1-oxido-4-thiomorpholinyl)-7-oxo-2,3-
Dihydro-7H-pyrido[3,2,1-ij]-1,3
, 4-benzoxadiazine-6-carboxylic acid or a pharmaceutically acceptable salt thereof, or a hydrate or solvate of a compound thereof or a salt thereof. Compound. 68), 9-fluoro-3-methyl-7-oxo-10
-[4-(2-oxo-n-propyl)-1-piperazinyl]-2,3-dihydro-7H-pyrido[3,2,1
-ij]-1,3,4-benzoxadiazine-6-carboxylic acid or a pharmaceutically acceptable salt thereof, or a hydrate or solvate of a compound thereof or a salt thereof. A compound according to scope 1. 69), 10-(3-chloro-1-pyrrolidinyl)-9
-Fluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido[3,2,1-ij]-1,3,4-
Claim 1 is a hydrate or solvate of benzoxadiazine-6-carboxylic acid or a pharmaceutically acceptable salt thereof, or a compound thereof or a salt thereof.
Compounds described in Section. 70), 9-fluoro-3-(2-fluoroethyl)-
10-(4-Methyl-1-piperazinyl)-7-oxo-2,3-dihydro-7H-pyrido[3,2,1-ij
]-1,3,4-benzoxadiazine-6-carboxylic acid or a pharmaceutically acceptable salt thereof, or a hydrate or solvate of a compound thereof or a salt thereof. Compound according to item 1. 71), 10-(4-amino-1piperidyl)-9-fluoro-3-methyl-7-oxo-2,3-dihydro-
7H-pyrido[3,2,1-ij]-1,3,4-benzoxadiazine-6-carboxylic acid or a pharmaceutically acceptable salt thereof, or a hydrate of the compound or a salt thereof or the compound according to claim 1, which is a solvate. 72), 9-fluoro-3-methyl-10-[4-(methylamino)-1-piperidyl]-7-oxo-2,3
-dihydro-7H-pyrido[3,2,1-ij]-1,
Claim 1 which is a hydrate or solvate of 3,4-benzoxadiazine-6-carboxylic acid or a pharmaceutically acceptable salt thereof, or a compound thereof or a salt thereof. compound. 73), 10-[4-(ethylamino)-1-piperidyl]-9-fluoro-3-methyl-7-oxo-2,3
-dihydro-7H-pyrido[3,2,1-ij]-1,
Claim 1 which is a hydrate or solvate of 3,4-benzoxadiazine-6-carboxylic acid or a pharmaceutically acceptable salt thereof, or a compound thereof or a salt thereof. compound. 74), 10-[3[(ethylmethylamino)methyl]
-1-pyrrolidinyl)-9-fluoro-3-methyl-7
-oxo-2,3-dihydro-7H-pyrido[3,2,
1-ij]-1,3,4-benzoxadiazine-6-
The compound according to claim 1, which is a hydrate or solvate of a carboxylic acid or a pharmaceutically acceptable salt thereof, or a compound thereof or a salt thereof. 75), 10-(3-amino-4-hydroxy-1-pyrrolidinyl)-9-fluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido[3,2,1-ij
]-1,3,4-benzoxadiazine-6-carboxylic acid or a pharmaceutically acceptable salt thereof, or a hydrate or solvate of a compound thereof or a salt thereof. Compound according to item 1. 76), 9-fluoro-10-[3-hydroxy-4-
(Methylamino)-1-pyrrolidinyl]-3-methyl-
7-oxo-2,3-dihydro-7H-pyrido[3,2
,1-ij]-1,3,4-benzoxadiazine-6
- The compound according to claim 1, which is a carboxylic acid or a pharmaceutically acceptable salt thereof, or a hydrate or solvate of the compound or a salt thereof. 77), 9-fluoro-3-methyl-7-oxo-10
-(4-thiomorpholinyl-2,3-dihydro-7H-
Pyrido[3,2,1-ij]-1,3,4-benzoxadiazine-6-carboxylic acid or a pharmaceutically acceptable salt thereof, or a hydrate or solvent of the compound or a salt thereof 1. The compound according to claim 1, which is a conjugate. 78), 10-[2,6-dimethyl-4-morpholinyl)-9-fluoro-3-methyl-7-oxo-2,3-
Dihydro-7H-pyrido[3,2,1-ij]-1,3
, 4-benzoxadiazine-6-carboxylic acid or a pharmaceutically acceptable salt thereof, or a hydrate or solvate of a compound thereof or a salt thereof. Compound. 79), 10-[3-(acetylaminomethyl)-1-
pyrrolidinyl)-9-fluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido[3,2,1-i
j]-1,3,4-benzoxadiazine-6-carboxylic acid or a pharmaceutically acceptable salt thereof, or a hydrate or solvate of a compound thereof or a salt thereof A compound according to item 1. 80), 10-[[2-(dimethylamino)ethyl]methylamino]-9-fluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido[3,2,1-ij
]-1,3,4-benzoxadiazine-6-carboxylic acid or a pharmaceutically acceptable salt thereof, or a hydrate or solvate of a compound thereof or a salt thereof. Compound according to item 1. 81), 9-fluoro-3-methyl-7-oxo-10
-(3-oxo-1-piperazinyl)-2,3-dihydro-7H-pyrido[3,2,1-ij]-1,3,4-
Claim 1 is a hydrate or solvate of benzoxadiazine-6-carboxylic acid or a pharmaceutically acceptable salt thereof, or a compound thereof or a salt thereof.
Compounds described in Section. 82), 9-fluoro-2-(hydroxymethyl)-3
-Methyl-10-(4-methyl-1-piperazinyl)-
7-oxo-2,3-dihydro-7H-pyrido[3,2
,1-ij]-1,3,4-benzoxadiazine-6
- The compound according to claim 1, which is a carboxylic acid or a pharmaceutically acceptable salt thereof, or a hydrate or solvate of the compound or a salt thereof. 83), 2-[(dimethylamino)methyl]-9-fluoro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-2,3-dihydro-7H-pyrido[3,2 , 1-ij]-1,3,4-benzoxadiazine-6-carboxylic acid or a pharmaceutically acceptable salt thereof, or a hydrate or solvate of a compound thereof or a salt thereof A compound according to claim 1. 84), 10-[3-(benzyloxycarbonylamino)-1-pyrrolidinyl]-9-fluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido[3,
2,1-ij]-1,3,4-benzoxadiazine-
The compound according to claim 1, which is a hydrate or solvate of 6-carboxylic acid or a pharmaceutically acceptable salt thereof, or a compound thereof or a salt thereof. 85), 9-fluoro-3-methyl-7-oxo-10
-(4-phenacyl-1-piperazinyl)-2,3-dihydro-7H-pyrido[3,2,1-ij]-1,3,
The compound according to claim 1, which is a hydrate or solvate of 4-benzoxadiazine-6-carboxylic acid or a pharmaceutically acceptable salt thereof, or a compound thereof or a salt thereof. . 86), 9-fluoro-3-methyl-10-[4-(4
-nitrobenzyl)-1-piperazinyl]-7-oxo-213-dihydro-7H-pyrido[3,2,1-ij
]-1,3,4-benzoxadiazine-6-carboxylic acid or a pharmaceutically acceptable salt thereof, or a hydrate or solvate of a compound thereof or a salt thereof. Compound according to item 1. 87), 10-[4-(3-carboxypropionyl)
-1-piperazinyl]-9-fluoro-3-methyl-7
-oxo-2,3-dihydro-7H-pyrido[3,2,
1-ij]-1,3,4-benzoxadiazine-6-
The compound according to claim 1, which is a hydrate or solvate of a carboxylic acid or a pharmaceutically acceptable salt thereof, or a compound thereof or a salt thereof. 88), 10-(4-acetyl-1-piperazinyl)-
9-Fluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido[3,2,1-ij]-1,3,4
The compound according to claim 1, which is a hydrate or solvate of -benzoxadiazine-6-carboxylic acid or a pharmaceutically acceptable salt thereof, or a compound thereof or a salt thereof. 89), 9-fluoro-10-(4-methoxy-1-piperidyl)-3-methyl-7-oxo-2,3-dihydro-7H-pyrido[3,2,1-ij]-1,3, 4-
Claim 1 is a hydrate or solvate of benzoxadiazine-6-carboxylic acid or a pharmaceutically acceptable salt thereof, or a compound thereof or a salt thereof.
Compounds described in Section. 90), 9-fluoro-2,3-dimethyl-10-(4
-methyl-1-piperazinyl)-7-oxo-2,3-
Dihydro-7H-pyrido[3,2,1-ij]-1,3
, 4-benzoxadiazine-6-carboxylic acid or a pharmaceutically acceptable salt thereof, or a hydrate or solvate of a compound thereof or a salt thereof. Compound. 91), 9-fluoro-2,3-dimethyl-7-oxo-10-(1-piperazinyl)-2,3-dihydro-7
H-pyrido[3,2,1-ij]-1,3,4-benzoxadiazine-6-carboxylic acid or a pharmaceutically acceptable salt thereof, or a hydrate of the compound or a salt thereof or the compound according to claim 1, which is a solvate. 92), ethyl 10-[3-(benzyloxycarbonylamino)-1-pyrrolidinyl]-9-fluoro-3
-Methyl-7-oxo-2,3-dihydro-7H-pyrido[3,2,1-ij]-1,3,4-benzoxadiazine-6-carboxylate or a pharmaceutically acceptable thereof The compound according to claim 1, which is a salt, or a hydrate or solvate of the compound or a salt thereof. 93), ethyl 10-(3-amino-1-pyrrolidinyl)-9-fluoro-3-methyl-7-oxo-2,3
-dihydro-7H-pyrido[3,2,1-ij]-1,
Claim 1 which is a hydrate or solvate of 3,4-benzoxadiazine-6-carboxylate or a pharmaceutically acceptable salt thereof, or a compound thereof or a salt thereof. compound. 94), benzyl 9-fluoro-10-(3-hydroxy-1-pyrrolidinyl)-3-methyl-7-oxo-
2,3-dihydro-7H-pyrido[3,2,1-ij]
-1,3,4-benzoxadiazine-6-carboxylate or a pharmaceutically acceptable salt thereof, or a hydrate or solvate of a compound thereof or a salt thereof Claim 1 Compounds described in Section. 95), benzyl 10-(3-chloro-1-pyrrolidinyl]-9-fluoro-3-methyl-7-oxo-2,
3-dihydro-7H-pyrido[3,2,1-ij]-1
, 3,4-benzoxadiazine-6-carboxylate or a pharmaceutically acceptable salt thereof, or a hydrate or solvate of the compound or a salt thereof. Compounds described. 96), pivaloyloxymethyl=10-[3-(benzyloxycarbonylamino)-1-pyrrolidinyl]-
9-Fluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido[3,2,1-ij]-1,3,4
-Benzoxadiazine-6-carboxylate or a pharmaceutically acceptable salt thereof, or a hydrate or solvate of the compound or a salt thereof. 97), pivaloyloxymethyl 10-(3-amino-1-pyrrolidinyl)-9-fluoro-3-methyl-7
-oxo-2,3-dihydro-7H-pyrido[3,2,
1-ij]-1,3,4-benzoxadiazine-6-
carboxylate or a pharmaceutically acceptable salt thereof;
Alternatively, the compound according to claim 1, which is a hydrate or solvate of the compound or a salt thereof. 98), 10-[3-[(4-aminobenzyl)amino]-1-pyrrolidinyl]-9-fluoro-3-methyl-
7-oxo-2,3-dihydro-7H-pyrido[3,2
,1-ij]-1,3,4-benzoxadiazine-6
-carboxylate or a pharmaceutically acceptable salt thereof, or a hydrate or solvate of the compound or a salt thereof. 99), 9-fluoro-10-[3-[[(dimethylamino)methylene]amino]-1-pyrrolidinyl]-3-
Methyl-7-oxo-2,3-dihydro-7H-pyrido[3,2,1-ij]-1,3,4-benzoxadiazine-6-carboxylic acid or a pharmaceutically acceptable salt thereof , or a hydrate or solvate of the compound or a salt thereof. 100), 9-fluoro-3-methyl-10-[3-(
4-methyl-1-piperazinyl)-1-pyrrolidinyl]
-7-oxo-2,3-dihydro-7H-pyrido[3,
2,1-ij]-1,3,4-benzoxadiazine-
The compound according to claim 1, which is a hydrate or solvate of 6-carboxylic acid or a pharmaceutically acceptable salt thereof, or a compound thereof or a salt thereof. 101), 10-(3-amino-3-methyl-1-pyridinyl)-9-fluoro-3-methyl-7-oxo-2
,3-dihydro-7H-pyrido[3,2,1-ij]-
Claim 1 is a hydrate or solvate of 1,3,4-benzoxadiazine-6-carboxylic acid or a pharmaceutically acceptable salt thereof, or a compound thereof or a salt thereof. Compounds described in. 102), 10-(trans-3-amino-4-methyl-1-pyrrolidinyl)-9-fluoro-3-methyl-7
-oxo-2,3-dihydro-7H-pyrido[3,2,
1-ij]-1,3,4-benzoxadiazine-6-
The compound according to claim 1, which is a hydrate or solvate of a carboxylic acid or a pharmaceutically acceptable salt thereof, or a compound thereof or a salt thereof. 103), 10-(trans-3-amino-4-phenyl-1-pyrrolidinyl)-9-fluoro-3-methyl-
7-oxo-2,3-dihydro-7H-pyrido[3,2
,1-ij]-1,3,4-benzoxadiazine-6
- The compound according to claim 1, which is a carboxylic acid or a pharmaceutically acceptable salt thereof, or a hydrate or solvate of the compound or a salt thereof. 104), 9-fluoro-3-methyl-10-[3-methyl-3[(methylamino)methyl]-1-pyrrolidinyl]-7-oxo-2,3-dihydro-7H-pyrido[
3,2,1-ij]-1,3,4-benzoxadiazine-6-carboxylic acid or a pharmaceutically acceptable salt thereof, or a hydrate or solvate of the compound or a salt thereof The compound according to claim 1, which is 105), 9-fluoro-3-methyl-10-[trans-3-[(methylamino)methyl]-4-phenyl-
1-pyridinyl]-7-oxo-2,3-dihydro-7
H-pyrido[3,2,1-ij]-1,3,4-benzoxadiazine-6-carboxylic acid or a pharmaceutically acceptable salt thereof, or a hydrate of the compound or a salt thereof or the compound according to claim 1, which is a solvate. 106), 10-(trans-3-amino-4-methoxy-1-pyrrolidinyl)-9-fluoro-3-methyl-
7-oxo-2,3-dihydro-7H-pyrido[3,2
,1-ij]-1,3,4-benzoxadiazine-6
- The compound according to claim 1, which is a carboxylic acid or a pharmaceutically acceptable salt thereof, or a hydrate or solvate of the compound or a salt thereof. 107), 10-(trans-3-amino-4-hydroxy-1-pyrrolidinyl)-9-fluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido[3,
2,1-ij]-1,3,4-benzoxadiazine-
The compound according to claim 1, which is a hydrate or solvate of 6-carboxylic acid or a pharmaceutically acceptable salt thereof, or a compound thereof or a salt thereof. 108), General Formula (III) ▲Mathematical formulas, chemical formulas, tables, etc.▼(III) In the formula, R^1 represents a hydrogen atom or a carboxy protecting group; R^2 is substituted with a hydrogen atom or a halogen atom R^3 and R^4 each independently represent a lower alkyl group which may be substituted with a hydrogen atom, a hydroxyl group, or a substituted or unsubstituted amino group; ; and X and X' are the same or different and represent a halogen atom. 109), General Formula (V) ▲Mathematical formulas, chemical formulas, tables, etc.▼(V) In the formula, R^1 represents a hydrogen atom or a carboxy protecting group; R^2 is substituted with a hydrogen atom or a halogen atom. X represents a halogen atom; and R^5 and R^6 are each independently substituted with a hydrogen atom, a hydroxyl group, a lower alkoxy group, or a substituted or unsubstituted amino group; or R^5 and R^6 may be combined with adjacent nitrogen atoms to form a 5- to 7-membered heterocycle; may be substituted with one or more substituents, and the heterocycle may further include -NR^7-, -O-, -
S-, -SO-, -SO_2-, or -NR^7-
CO-[Here, R^7 is a hydrogen atom, a lower alkenyl group, an optionally substituted lower alkyl or aralkyl group, or the general formula (II) -(CH_2)nCOR^8(II) (in the formula, n is 0 to 4, and R^8 is a hydrogen atom, a lower alkoxy group, or an optionally substituted amino, lower alkyl, or aryl group). . 110), a compound according to any one of claims 1 to 107 as a pharmaceutically active substance. 111), compounds according to any one of claims 1 to 10 as pharmaceutically active substances for the treatment and prevention of infectious diseases. 112), (a) General formula (III) ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (III) In the formula, R^1, R^2, R^3, R^4 and X are within the scope of the claims. and X' represents a halogen atom; the amino group, hydroxyl group and/or carboxyl group in the formula may be protected. A compound represented by the general formula (IV ) ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (IV) In the formula, R^5 and R^6 have the same meanings as stated in claim 1, and react with an amine represented by (b) General formula (V) ▲ Numerical formula, chemical formula, table, etc. ▼ (V) In the formula, R^1, R^2, R^5, R^6 and X has the same meaning as stated in claim 1; and the amino group, hydroxyl group and/or carboxy group in the formula may be protected. A compound represented by the general formula (VI) ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (VI) In the formula, R^3 and R^4 have the same meaning as stated in claim 1, and a carbonyl compound represented by or its (c) to produce a compound of formula (I) in which R^7 is a group other than a hydrogen atom, by reacting with a polymer, acetal, ketal or enol ether, optionally removing the protecting group; is a hydrogen atom, the compound of formula (I) is substituent R^7^0 (where R
(d) R^5 and/or R^6 are lower alkyl groups (
or containing a di-lower alkylamino group or a lower alkoxy group),
Formulas in which R^5 and/or R^6 are hydrogen atoms, or contain an amino group, a lower alkyl group, or a hydroxyl group (
(e) A compound of formula (I) in which R^5R^6N- is a 5- to 7-membered heterocycle containing -SO- or -SO_2-;
(f) producing a compound of formula (I) having a free amino, hydroxyl and/or carboxyl group; (g) to produce a compound of formula (I) containing a halogen atom; , R^1 is a carboxy protecting group by halogenating the corresponding hydroxyl-substituted compound of formula (I) and optionally removing the protecting group R^1, or (h) containing an amino group. To prepare a compound of formula (I), the nitro group of the corresponding nitro-substituted compound of formula (I) is reduced or (i) the formula ▲ is a mathematical formula, chemical formula, table, etc. ▼ (where R ^5^0 and R^5^1 are lower alkyl groups or together with the nitrogen atom represent a 5- to 8-membered saturated N-heterocycle) compounds of formula (I) To produce the corresponding amino-substituted compound of formula (I), the general formula (VII) ▲There are mathematical formulas, chemical formulas, tables, etc.▼(VII) where R^5^0 and R^5 (j) to prepare a compound of formula (I) in which R^1 is a carboxy protecting group, by reacting with a reactive derivative of the formamide derivative of , where R^1 has the same meaning as above; ) to the corresponding esterification, or (k) a pharmaceutically acceptable salt, hydrate or solvate of a compound of formula (I) or a hydrate of said salt or Claim 1 characterized in that the compound of formula (I) is converted into a salt, hydrate or solvate or a hydrate or solvate of a salt thereof in order to produce a solvate. - A method for producing a compound described in any one of Items 107. 113), (a) to (k), (j), and (k). 114), a pharmaceutical preparation characterized in that it contains a compound according to any one of claims 1 to 107. 115), a pharmaceutical preparation for the treatment and prevention of infectious diseases containing a compound according to any one of claims 1 to 107. 116), the use of compounds according to any one of claims 1 to 107 in the treatment and prevention of diseases. 117), the use of a compound according to any one of claims 1 to 107 in the treatment and prevention of infectious diseases. 118), the use of a compound according to any one of claims 1 to 107 for the manufacture of a medicament for the treatment and prophylaxis of infectious diseases. 119), a compound according to any one of claims 1 to 107, produced by the method according to claim 112 or a method chemically equivalent thereto.