JPH111483A - Production of tricyclic compound - Google Patents

Abstract

PROBLEM TO BE SOLVED: To enable the obtaining of a tricyclic compound useful as a therapeutic agent for nephropathy or arteriosclerosis in a small number of steps at a lower production cost by using a compound having sulfonyl group. SOLUTION: A compound represented by formula I (the A-ring may have a substituent group; the B-ring may have oxo; R<1> is H, a halogen, a substitutable hydrocarbon or an acyl) is reacted with a compound represented by formula II (Z is an eliminable group; X is a substitutable bivalent hydrocarbon; the Y-ring is a substitutable 5- or 6-membrered heterocyclic ring; R is a substitutable hydrocarbon) to provide a tricyclic compound represented by formula III. The reaction is carried out by using the compound represented by formula II in an amount of 1-10 equiv. based on the compound represented by formula I in the presence of a base such as triethylamine in a solvent such as toluene at -20 to +200 deg.C for 0.5-6 hr. Thereby, the compound represented by formula III is obtained in high yield.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a method for producing a tricyclic compound having excellent platelet-derived growth factor (PDGF) inhibitory action, renal disease improving action, lipid lowering action, and the like, and useful for producing the same. Intermediates and a process for producing the same.

[0002]

2. Description of the Related Art PCT International Publication No. WO 96/025
No. 42 discloses an excellent platelet-derived growth factor (PDG).
F) A method for producing a tricyclic compound useful as a pharmaceutical having an inhibitory action, an antihypertensive action, an ameliorating action on nephropathy, a cholesterol lowering action, and the like is described. However, the PCT
In the method described in the publication, the number of steps is large, and
There is a drawback that expensive raw materials are frequently used and the production cost is high.

[0003]

Under the circumstances described above, there is an urgent need for a process for producing the above-mentioned tricyclic compound which uses a small number of steps and uses inexpensive raw materials.

[0004]

Means for Solving the Problems In view of the above circumstances, the present inventors have made various studies and found that the compound represented by the general formula (III)

Embedded image [Wherein, Z is a leaving group, X is a divalent hydrocarbon group which may have a substituent, and Y ring is a nitrogen-containing 5- or 6-membered heterocyclic ring which may have a substituent. R represents a hydrocarbon group which may have a substituent. By using a novel compound represented by the formula or a salt thereof, the number of steps is small,
At a lower production cost, and found that the tricyclic compound can be obtained in good yield, as a result of further research,
The present invention has been completed.

That is, the present invention relates to (1) the general formula (II)

Embedded image [In the formula, ring A may have a substituent, ring B may have one oxo group, and R ¹ may have a hydrogen atom, a halogen atom, and a substituent. Shows a hydrocarbon group or an acyl group. And a salt thereof and a compound represented by the general formula (III)

Embedded image [Wherein, Z is a leaving group, X is a divalent hydrocarbon group which may have a substituent, and Y ring is a nitrogen-containing 5- or 6-membered heterocyclic ring which may have a substituent. And R represents a hydrocarbon group which may have a substituent. A compound represented by the general formula (I):

Embedded image [The symbols in the formula are as defined above. And (2) ring A is halogen, C
_1-6 alkyl, halogeno-C _1-6 alkyl, C _1-6 alkoxy, halogeno-C _1-6 alkoxy, C _1-6 alkylthio, halogeno-C _1-6 alkylthio, hydroxy, carboxy, cyano, nitro, amino , Mono- or di-C
_1-6 alkylamino, formyl, mercapto, C _1-6 alkyl - carbonyl, C _1-6 alkoxy - carbamoyl - carbonyl, sulfo, C _1-6 alkylsulfonyl, carbamoyl and mono- - or di -C _1-6 alkyl The ring B may be substituted with one to three selected groups,

Embedded image A ring represented by the formula: wherein X is (1) a C _1-15 alkylene group, a C _2-16 alkenylene group or a C _2-16 alkynylene group which may be substituted by 1 to 5 C _1-6 alkyl or phenyl groups. , (2) halogen, C _1-6 alkyl, C _1-6 alkoxy, C _1-6 alkylthio, hydroxy, carboxy, cyano, nitro, amino, mono- or di-C _1-6 alkylamino, formyl, mercapto, C _1-6 alkyl-carbonyl, C _1-6 alkoxy-carbonyl, sulfo, C
_1-6 alkylsulfonyl, carbamoyl and mono- - or di -C _1-6 alkyl - 1 selected from carbamoyl
Or a phenylene group which may be substituted with 4 to 4 groups, or (3) a divalent group formed by combining these groups, wherein the Y ring is halogen, C _1-6 alkyl, halogeno-C _1-6
Alkyl, C _1-6 alkoxy, halogeno-C _1-6 alkoxy, C _1-6 alkylthio, halogeno-C _1-6 alkylthio, hydroxy, carboxy, cyano, nitro, amino, mono- or di-C _1-6 alkyl 1 to 1 selected from amino, formyl, mercapto, C _1-6 alkyl-carbonyl, C _1-6 alkoxy-carbonyl, sulfo, C _1-6 alkylsulfonyl, carbamoyl and mono- or di-C _1-6 alkyl-carbamoyl Piperidine, pyrrolidine or pyridine optionally substituted by three groups, wherein R is nitro, hydroxy, cyano, carbamoyl, mono- or di-C _1-6 alkyl-carbamoyl,
Carboxy, C _1-6 alkoxy-carbonyl, sulfo,
Halogen, C _1-6 alkoxy, phenoxy, halogeno-
Phenoxy, C _1-6 alkylthio, mercapto, phenylthio, pyridylthio, C _1-6 alkylsulfinyl,
C _1-6 alkylsulfonyl, amino, C _1-6 acylamino, mono- - or di -C _1-6 alkylamino, 4- to 6-membered cyclic amino group, C _1-7 acyl, benzoyl, nitrogen atom, sulfur atom and oxygen 5- or 6-membered monocyclic aromatic heterocyclic group having 1 to 4 heteroatoms selected from atoms and 5- or 6-membered having 1 or 2 heteroatoms selected from nitrogen, sulfur and oxygen A C _1-15 alkyl group which may be substituted with 1 to 5 groups selected from a bicyclic aromatic heterocyclic group formed by condensing an aromatic heterocyclic ring and a benzene ring, C _3-8 Cycloalkyl group, C _2-18 alkenyl group, C _7-16 aralkyl group or C
_{In the 6-14} aryl group, a C _7-16 aralkyl group or a C _6-14 aryl group is, in addition to these substituents, a C _1-6 alkyl group,
May be substituted with a halogeno-C _1-6 alkyl group or an oxo group, wherein R ¹ is (1) a hydrogen atom, (2) a halogen atom,
(3) an acyl group derived from a carboxylic acid or (4) nitro,
Hydroxy, cyano, carbamoyl, mono- or di-
C _1-6 alkyl-carbamoyl, carboxy, C _1-6 alkoxy-carbonyl, sulfo, halogen, C _1-6 alkoxy, phenoxy, halogeno-phenoxy, C _1-6 alkylthio, mercapto, phenylthio, pyridylthio,
C _1-6 alkylsulfinyl, C _1-6 alkylsulfonyl, amino, C _1-6 acylamino, mono- or di-C
5- or 6-membered monocyclic aromatic having 1 to 4 heteroatoms selected from _1-6 alkylamino, 4- to 6-membered cyclic amino, _C1-7 acyl, benzoyl, nitrogen, sulfur and oxygen Bicyclic aromatic heterocycle formed by condensing a benzene ring with a heterocyclic group and a 5- or 6-membered aromatic heterocycle having one or two heteroatoms selected from a nitrogen atom, a sulfur atom and an oxygen atom C optionally substituted with 1 to 5 groups selected from ring groups
_1-15 alkyl group, C _3-8 cycloalkyl group, C _2-18 alkenyl group, C _7-16 aralkyl group or C _6-14 aryl group, and C _7-16 aralkyl group or C _6-14 aryl group In addition to these substituents, a C _1-6 alkyl group, halogeno-C
(1) The method according to the above (1), which may be substituted with a _1-6 alkyl group or an oxo group, and wherein Z is a halogen atom, a C _1-4 alkylsulfonyloxy group or a C _6-10 arylsulfonyloxy group. 3) ring A is unsubstituted and ring B is a compound of the formula

Embedded image Wherein R ¹ is a hydrogen atom or a C _1-6 alkyl group, X is a C _1-6 alkylene group, Y ring is piperidine and R is a halogeno-C _1-6 alkyl group. Production method, (4) ring A is halogen, C _1-6 alkyl, C _1-4
Alkylthio, C _1-4 alkoxy, hydroxy, carboxy, nitro and amino may be substituted, and R ¹ is selected from (1) hydrogen atom, (2) halogen, hydroxy, carboxy, nitro and amino. A C _1-10 alkyl group or a C _6-14 aryl group, a (4) C _1-6 alkoxy-carbonyl group or a (5) C _1-6 alkanoyl group, each of which may be substituted with The atom, C _1-4 alkylsulfonyloxy group or C _6-10 arylsulfonyloxy group may be substituted with a group in which X is selected from halogen, hydroxy, C _1-4 alkyl and C _6-14 aryl group. C _1-6 alkylene group, Y ring nitrogen-containing 6-membered heterocyclic ring, and R is (i) halogen, (ii) cyano, (iii) hydroxy, optionally substituted by (iv) a halogen C _1-6 Alkyl, (v) halogen Are unprotected C _1-4 alkoxy, each substituted with (vi) C _6-14 aryl, (vii) optionally esterified carboxy and also be (viii) 5 to group selected from 6-membered heterocyclic group An optionally _substituted C _1-15 alkyl group, C _3-8 cycloalkyl group, C _2-10 alkenyl group, C _6-14 aryl group or C
The production method according to the above (1), which is a _7-16 aralkyl group,

(5) Ring A may be substituted by a group selected from halogen and C _1-4 alkyl, and ring B is

Embedded image Wherein R ¹ is a hydrogen atom, a C _1-6 alkyl group or a C _6-14 aryl group, and X is a C _1- optionally substituted with a group selected from halogen, hydroxy and C _1-4 alkyl. _{A 6-} alkylene group, wherein the Y ring is a nitrogen-containing 6-membered heterocyclic ring, and R is a C _1-10 alkyl group which may be each substituted with a group selected from halogen, hydroxy and carboxy which may be esterified. (1) The production method described in (1), (6) Ring A is unsubstituted, and Ring B is a compound of the formula

Embedded image Wherein R ¹ is a hydrogen atom, Y ring is a nitrogen-containing 6-membered heterocyclic ring and R is a C _1-6 alkyl group substituted with halogen, (7) Ring A Is unsubstituted, B
Ring is a formula

Embedded image Wherein R ¹ is a hydrogen atom, Z is a chlorine atom, X is an ethylene group, Y ring is a piperidine and R is a trifluoromethyl group, (8) in the presence of a base The production method according to the above (1),

(9) General formula

Embedded image [Wherein, Z is a leaving group, X is a divalent hydrocarbon group which may have a substituent, and Y ring is a nitrogen-containing 5- or 6-membered heterocyclic ring which may have a substituent. And R represents a hydrocarbon group which may have a substituent. Or a salt thereof, (10) wherein X is (1) a C _1-15 alkylene group, a C _2-16 alkenylene group which may be substituted with 1 to 5 C _1-6 alkyl or phenyl, or C _2-16 alkynylene group, (2) halogen, C _1-6 alkyl, C _1-6 alkoxy,
C _1-6 alkylthio, hydroxy, carboxy, cyano, nitro, amino, mono- or di-C _1-6 alkylamino, formyl, mercapto, C _1-6 alkyl-carbonyl, C _1-6 alkoxy-carbonyl, sulfo, C _1-6
A phenylene group which may be substituted with 1 to 4 groups selected from alkylsulfonyl, carbamoyl and mono- or di-C _1-6 alkyl-carbamoyl, or (3) a divalent group formed by combining these groups Of the
Y ring is halogen, C _1-6 alkyl, halogeno-C _1-6 alkyl, C _1-6 alkoxy, halogeno-C _1-6 alkoxy,
C _1-6 alkylthio, halogeno-C _1-6 alkylthio, hydroxy, carboxy, cyano, nitro, amino, mono- or di-C _1-6 alkylamino, formyl, mercapto, C _1-6 alkyl-carbonyl, C _{1 -6} alkoxy-
Piperidine, pyrrolidine or pyridine which may be substituted with 1 to 3 groups selected from carbonyl, sulfo, C _1-6 alkylsulfonyl, carbamoyl and mono- or di-C _1-6 alkyl-carbamoyl; , Hydroxy, cyano, carbamoyl, mono- or di-C _1-6 alkyl-carbamoyl, carboxy,
C _1-6 alkoxy-carbonyl, sulfo, halogen, C
_1-6 alkoxy, phenoxy, halogeno-phenoxy,
C _1-6 alkylthio, mercapto, phenylthio, pyridylthio, C _1-6 alkylsulfinyl, C _1-6 alkylsulfonyl, amino, C _1-6 acylamino, mono- - or di -C _1-6 alkylamino, 4- to 6-membered A 5- or 6-membered monocyclic aromatic heterocyclic group having 1 to 4 heteroatoms selected from cyclic amino, C _1-7 acyl, benzoyl, nitrogen atom, sulfur atom and oxygen atom, and nitrogen atom, sulfur atom and 1 to 5 groups selected from bicyclic aromatic heterocyclic groups formed by condensing a benzene ring with a 5- or 6-membered aromatic heterocycle having 1 or 2 heteroatoms selected from oxygen atoms C optionally substituted with
_1-15 alkyl group, C _3-8 cycloalkyl group, C _2-18 alkenyl group, C _7-16 aralkyl group or C _6-14 aryl group, and C _7-16 aralkyl group or C _6-14 aryl group In addition to these substituents, a C _1-6 alkyl group, halogeno-C _1-6
And may be substituted with an alkyl group or an oxo group.
Is a halogen atom, a C _1-4 alkylsulfonyloxy group or a C _6-10 arylsulfonyloxy group, wherein (9)
(11) X is a C _1-6 alkylene group, Y ring is piperidine and R is a halogeno-C _1-6 alkyl group, (12) X is an ethylene group,
The compound according to the above (9), wherein the Y ring is piperidine and R is a trifluoromethyl group, (13) the general formula (IV)

Embedded image [Wherein, Z is a leaving group, X is a divalent hydrocarbon group which may have a substituent, and Y ring is a nitrogen-containing 5- or 6-membered heterocyclic ring which may have a substituent. Is shown. Wherein a sulfonylating agent containing a hydrocarbon group which may have a substituent is allowed to act on the compound represented by the formula (I) or a salt thereof:

Embedded image [Wherein, R represents a hydrocarbon group which may have a substituent,
Other symbols are as defined above. And (14) a method for producing a compound represented by the formula (I) or a salt thereof,
It relates to the use of the compound represented by I) or a salt thereof.

In the above formula, the ring A may have a substituent. Examples of the substituent that the ring A may have include, for example,
(1) halogen atom (eg, fluorine, chlorine, bromine, iodine, etc.), (2) C _1-6 alkyl (eg, methyl, ethyl, propyl, isopropyl, butyl, etc.), (3) 1 to 5 halogens halogeno -C _1-6 alkyl such as C _1-6 alkyl substituted with atoms (e.g., trifluoromethyl, trichloromethyl, etc.), (4) C _1-6 alkoxy (e.g., methoxy, ethoxy, propoxy, isopropoxy Such),
(5) 1 to 5 halogeno -C _1-6 alkoxy such as C _1-6 alkoxy substituted with halogen atom (e.g., trifluoromethoxy, trichloromethoxy, etc.), (6) C _1-6
Alkylthio (e.g., methylthio, ethylthio, propylthio, isopropylthio, etc.), (7) 1 to halogeno -C _1-6 alkylthio (e.g., such as five C _1-6 alkylthio substituted by halogen atoms, trifluoromethylthio, Trichloromethylthio), (8) hydroxy, (9)
Carboxy, (10) cyano, (11) nitro, (12) amino, (1
3) mono- or di-C _1-6 alkylamino (eg, methylamino, ethylamino, dimethylamino, diethylamino, etc.), (14) formyl, (15) mercapto, (16) _C1-6
Alkyl-carbonyl (eg, acetyl, propionyl,
Butyryl, etc.), (17) C _1-6 alkoxy-carbonyl (eg, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, etc.), (18) sulfo, (19) C _1-6 alkylsulfonyl (eg, methylsulfonyl, ethylsulfonyl) , Propylsulfonyl, etc.), (20) carbamoyl,
(21) Mono- or di-C _1-6 alkyl-carbamoyl (eg, N-methylcarbamoyl, N-ethylcarbamoyl, N, N-dimethylcarbamoyl, N, N-diethylcarbamoyl and the like) and the like. Ring A may be substituted with 1 to 3 identical or different substitutable positions with these substituents.

In the above formula, the ring B may have one oxo group. As the ring represented by ring B, for example, a nitrogen-containing 5- or 6-membered heterocyclic ring, more specifically, a compound represented by the formula

Embedded image And the like, among which the formula

Embedded image A ring represented by

Embedded image The ring represented by is commonly used.

In the above formula, X represents a divalent hydrocarbon group which may have a substituent. Examples of the “divalent hydrocarbon group” in the “divalent hydrocarbon group which may have a substituent” represented by X include a C _1-15 alkylene group (eg, methylene, ethylene, propylene, Butylene, pentamethylene, hexamethylene, heptamethylene, octamethylene, etc.), C _2-16 alkenylene groups (eg, vinylene, propenylene, 1-butenylene, 2-butenylene,
1-pentenylene, 2-pentenylene, 3-pentenylene, etc.), C _2-16 alkynylene group (eg, ethynylene, propynylene, 1-butynylene, 2-butynylene, 1-pentynylene, 2-pentynylene, 3-pentynylene, etc.) A divalent chain hydrocarbon group, a phenylene group, or a divalent group formed by combining these groups is used. Preferably, for example, a C _1-15 alkylene group (for example, methylene, ethylene, propylene, butylene, pentamethylene, hexamethylene, heptamethylene, octamethylene, etc.) and the like are more preferred, and a C _1-6 alkylene group (eg, , Methylene, ethylene, propylene, etc.). The “divalent chain hydrocarbon group” may have, for example, 1 to 5 C _1-6 alkyl groups (eg, methyl, ethyl, propyl, isopropyl, butyl, etc.), phenyl groups and the like.

The "phenylene group" includes, for example, (1) a halogen atom (eg, fluorine, chlorine, bromine, iodine, etc.),
(2) C _1-6 alkyl (eg, methyl, ethyl, propyl, isopropyl, butyl, etc.), (3) C _1-6 alkoxy (eg,
Methoxy, ethoxy, propoxy, isopropoxy, etc.), (4) C _1-6 alkylthio (eg, methylthio, ethylthio, propylthio, isopropylthio, etc.), (5) hydroxy, (6) carboxy, (7) cyano, (8 ) Nitro, (9)
Amino, (10) mono- or di-C _1-6 alkylamino (eg, methylamino, ethylamino, dimethylamino,
Diethylamino, etc.), (11) formyl, (12) mercapto, (13) C _1-6 alkyl - carbonyl (e.g., acetyl,
(14) C _1-6 alkoxy-carbonyl (eg, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, etc.), (15) sulfo, (1
6) C _1-6 alkylsulfonyl (eg, methylsulfonyl,
Ethylsulfonyl, propylsulfonyl, etc.), (17) carbamoyl and (18) mono- or di-C _1-6 alkyl-carbamoyl (eg N-methylcarbamoyl, N
-Ethylcarbamoyl, N, N-dimethylcarbamoyl, N, N-diethylcarbamoyl, etc.) and may have 1 to 4 substituents.

In the above formula, the Y ring represents a 5- or 6-membered nitrogen-containing heterocyclic ring which may have a substituent. The “nitrogen-containing 5- to 6-membered heterocycle” may be saturated or unsaturated,
For example, piperidine, pyrrolidine, pyridine and the like can be mentioned. More specifically, the expression

Embedded image As a group represented by, for example,

Embedded image And the like, preferably

Embedded image And especially

Embedded image Are commonly used. As the substituent which the “nitrogen-containing 5- or 6-membered heterocyclic ring” may have, for example, the same substituents as those which the above-mentioned ring A may have may be used.

In the above formula, R represents a hydrocarbon group which may have a substituent. Examples of the "hydrocarbon group" of the "hydrocarbon group which may have a substituent" represented by R include, for example, an alkyl group, a cycloalkyl group, an alkenyl group, an aralkyl group, an aryl group and the like. Examples of the “alkyl group” include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert.
-Butyl, pentyl, hexyl, heptyl, octyl,
A C _1-15 alkyl group such as nonyl, decyl, undecyl, tridecyl, tetradecyl and pentadecyl is used. Preferably, for example, methyl, ethyl, propyl,
Isopropyl, butyl, isobutyl, sec-butyl, ter
and C _1-6 alkyl groups such as t-butyl, pentyl and hexyl. As the "cycloalkyl group",
For example, a C _3-8 cycloalkyl group such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl and the like are used. As the “alkenyl group”, for example, a C _2-18 alkenyl group such as vinyl, allyl, isopropenyl, 3-butenyl, 3-octenyl, 9-octadecenyl and the like are used. Preferably, for example, vinyl, allyl, 2-butenyl, C _2-6 alkenyl group such as 3-butenyl.

The "aralkyl group" includes, for example, C
_{A 7-16} aralkyl group and the like are used. Specifically, for example, a phenyl-C _1-6 alkyl group such as benzyl, phenethyl, 3-phenylpropyl, 4-phenylbutyl and (1-naphthyl) methyl, And a naphthyl-C _1-6 alkyl group such as-(1-naphthyl) ethyl and 2- (2-naphthyl) ethyl. Preferable examples include a phenyl-C _1-6 alkyl group such as benzyl. Examples of the “aryl group” include phenyl, 1
-Aromatic monocyclic, bicyclic or tricyclic C _6-14 aryl groups such as -naphthyl, 2-naphthyl, phenanthryl and anthryl are used. Preferable examples include a C _6-10 aryl group such as phenyl.

Examples of the substituent which the “hydrocarbon group” may have include, for example, (1) nitro, (2) hydroxy, (3)
Cyano, (4) carbamoyl, (5) mono- or di-C _1-6
Alkyl-carbamoyl (eg, N-methylcarbamoyl, N-ethylcarbamoyl, N, N-dimethylcarbamoyl, N, N-diethylcarbamoyl, etc.), (6) carboxy, (7) C _1-6 alkoxy-carbonyl (eg, Methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, etc.), (8) sulfo, (9) halogen atom (eg, fluorine, chlorine, bromine, iodine, etc.), (10) C _1-6 alkoxy (eg, methoxy , Ethoxy, propoxy, isopropoxy, etc.), (11) phenoxy, (12) halogeno-phenoxy such as phenoxy substituted with 1 to 3 halogen atoms (eg, o-, m-
Or p-chlorophenoxy, o-, m- or p-bromophenoxy, etc.), (13) C _1-6 alkylthio (eg,
Methylthio, ethylthio, n-propylthio, isopropylthio, n-butylthio, etc.), (14) mercapto, (1
5) phenylthio, (16) pyridylthio, (17) C _1-6 alkylsulfinyl (e.g., methylsulfinyl, ethylsulfinyl etc.), (18) C _1-6 alkylsulfonyl (e.g.,
Methylsulfonyl, ethylsulfonyl, etc.), (19) amino, (20) _C1-6 acylamino (eg, acetylamino, propionylamino, etc.), (21) mono- or di- _C1-6.
4- to 6-membered alkylamino (eg, methylamino, ethylamino, dimethylamino, diethylamino, etc.), (22) cyclic amino (eg, 1-azetidinyl, 1-pyrrolidinyl, piperidino, morpholino, thiomorpholino, 1-piperazinyl, etc.) (23) C _1-7 acyl (eg, formyl, C _1-6 alkyl-carbonyl such as acetyl, etc.), (24) benzoyl and (25) heterocyclic group (eg, 2- or 3). -Thienyl, 2- or 3-furyl, 3-, 4- or 5-pyrazolyl, 2-, 4- or 5-thiazolyl, 3-, 4- or 5-isothiazolyl, 2-, 4- or 5-oxazolyl, 1,2,3-
Or 1,2,4-triazolyl, 1H- or 2H-
Tetrazolyl, 2-, 3- or 4-pyridyl, 2-,
1 to 4 selected from nitrogen, sulfur and oxygen, such as 4- or 5-pyrimidyl, 3- or 4-pyridazinyl, quinolyl, isoquinolyl and indolyl
5- or 6-membered monocyclic aromatic heterocyclic group having three heteroatoms, or a 5- or 6-membered aromatic heterocycle having one or two heteroatoms selected from nitrogen, sulfur and oxygen, and benzene And a bicyclic aromatic heterocyclic group formed by condensation with a ring.

As the substituent which the "aralkyl group" or the "aryl group" may have, in addition to these substituents, for example, a C _1-6 alkyl group (eg, methyl, ethyl, Propyl, isopropyl, butyl, etc.),
1 to a halogeno -C _1-6 alkyl group (examples of such five C _1-6 alkyl group substituted by a halogen atom, chloromethyl, trifluoromethyl, trichloromethyl, 2,2,
2-trifluoroethyl, 3,3,3-trifluoropropyl, pentafluoroethyl and the like), an oxo group and the like. The “hydrocarbon group” may have 1 to 5 of these substituents within a chemically acceptable range.

In the above formula, R ¹ represents a hydrogen atom, a halogen atom, a hydrocarbon group which may have a substituent or an acyl group. The "halogen atom" represented by R ¹ includes fluorine, chlorine, bromine and iodine. Examples of the “hydrocarbon group” in the “hydrocarbon group which may have a substituent” represented by R ¹ include the same as the hydrocarbon group represented by R described above. And the same substituents as the substituents which the hydrocarbon group represented by R may have. As the “acyl group” represented by R ¹ , for example, an acyl group derived from a carboxylic acid is used, and for example, an alkoxycarbonyl group, an alkylcarbamoyl group, an alkanoyl group and the like are used. As the "alkoxycarbonyl group", for example, methoxycarbonyl, ethoxycarbonyl,
C _1-6 alkoxy such as propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl, sec-butoxycarbonyl, tert-butoxycarbonyl, pentyloxycarbonyl, isopentyloxycarbonyl, neopentyloxycarbonyl, tert-pentyloxycarbonyl -A carbonyl group is used. Examples of the “alkylcarbamoyl group” include N-methylcarbamoyl, N-ethylcarbamoyl,
Mono-C _1-6 -N-alkyl-carbamoyl groups such as N-propylcarbamoyl, N-butylcarbamoyl and, for example, N, N-dimethylcarbamoyl, N, N-diethylcarbamoyl, N, N-dipropylcarbamoyl,
A di-C _1-6 -N, N-alkylcarbamoyl group such as N, N-dibutylcarbamoyl and N-ethyl-N-methylcarbamoyl and a dialkyl moiety are combined to form a 4- to 6-membered cyclic carbamoyl group (for example, -Azetidinylcarbonyl, morpholinocarbonyl, 1-pyrrolidinylcarbonyl, 1-piperidylcarbonyl, 1-piperazinylcarbonyl, etc.) are used. Examples of the “alkanoyl group” include formyl, C _1-9 alkyl-carbonyl group (eg, acetyl, propionyl, butyryl,
Isobutyryl, valeryl, isovaleryl, pivaloyl,
A C _1-10 alkanoyl group such as hexanoyl) is used. In the above formula, Z represents a leaving group. Examples of the leaving group represented by Z include a halogen atom such as fluorine, chlorine, bromine and iodine, a C _1-6 alkanoyloxy group such as acetyloxy and propionyloxy, and a C _7-11 arylcarbonyloxy group such as benzoyloxy. And a C _1-4 alkylsulfonyloxy group such as methanesulfonyloxy and ethanesulfonyloxy, and a C _6-10 arylsulfonyloxy group such as benzenesulfonyloxy and p-toluenesulfonyloxy.

Preferred examples of each group in the above formula are as follows. Ring A is unsubstituted or halogen, C _1-6
It is preferably substituted with a group selected from alkyl, C _1-4 alkylthio, C _1-4 alkoxy, hydroxy, carboxy, nitro and amino. Further, the ring A is
The case where it is unsubstituted or substituted with a group selected from halogen and C _1-4 alkyl is preferred. Ring A is most preferably an unsubstituted pyridine ring. Ring B has the formula

Embedded image The ring represented by is preferred. R ¹ is C _1-10 which may be substituted with (1) a hydrogen atom, (2) a group selected from halogen, hydroxy, carboxy, nitro and amino.
An alkyl group or a C _6-14 aryl group, a (3) C _1-6 alkoxy-carbonyl group or a (4) C _1-6 alkanoyl group is preferable. Further, R ¹ is a hydrogen atom, a C _1-6 alkyl group or a C _1-6 alkyl group. _{A 6-14} aryl group is preferred. R ¹ is most preferably a hydrogen atom.

Z is preferably a halogen atom, a C _1-4 alkylsulfonyloxy group or a C _6-10 arylsulfonyloxy group. Z is most preferably a chlorine atom. X is halogen, hydroxy, C _1-4 alkyl and C _6-14 a C _1-6 alkylene group optionally substituted by a group selected from aryl group preferably further, X is halogen, hydroxy and C _1-4 A C _1-6 alkylene group which may be substituted with a group selected from alkyl is preferred. X is most preferably an ethylene group. The Y ring is preferably a nitrogen-containing 6-membered heterocyclic ring,
Piperidine is most preferred. R is (i) halogen, (ii) cyano, (iii) hydroxy, (iv) C _1-6 alkyl, (v) alkyl optionally substituted with halogen, (vi) optionally substituted with halogen Alkoxy, (vii) C _6-14 aryl, (viii) optionally esterified carboxy and (ix) C _1-15 alkyl optionally substituted with a group selected from a 5- or 6-membered heterocyclic group. Groups, C _3-8 cycloalkyl groups, C _2-10 alkenyl groups, C _6-14 aryl groups or C _7-16 aralkyl groups are preferred. Further, R is preferably a C _1-10 alkyl group which may be substituted with a group selected from halogen, hydroxy and carboxy which may be esterified. R is more preferably a C _1-6 alkyl group substituted with halogen. R is most preferably a trifluoromethyl group. A ring is unsubstituted, B ring
Ring is a formula

Embedded image Wherein R ¹ is a hydrogen atom or a C _1-6 alkyl group, X is a C _1-6 alkylene group, Y ring is piperidine and R is a halogeno-C _1-6 alkyl group.

More preferred specific examples of compound (I) or a salt thereof include 1,2-dihydro-1- (1-trifluoromethanesulfonylpiperidin-4-ylmethyl)-
1,4,7b-Triazacyclopent [cd] indene-2
-One, 1,2-dihydro-1- [2- (1-trifluoromethanesulfonylpiperidin-4-yl) ethane-
1-yl] -1,4,7b-triazacyclopent [cd]
Inden-2-one, 1,2-dihydro-1- [3-
(1-trifluoromethanesulfonylpiperidine-4-
Yl) propan-1-yl] -1,4.7b-triazacyclopent [cd] inden-2-one, 4,5-dihydro-4- (1-trifluoromethanesulfonylpiperidin-4-ylmethyl) -3H -1,4,8b-Triazaacenaphthylene-3-one, 4,5-dihydro-4- [2
-(1-trifluoromethanesulfonylpiperidine-4
-Yl) ethane-1-yl] -3H-1,4,8b-triazaacenaphthylene-3-one, 4,5-dihydro-4
-[2- (1-trifluoromethanesulfonylpiperidin-4-yl) ethane-1-yl] -3H-1,4,8b
-Triazaacenaphthylene-5-one, 4,5-dihydro-4- [2- (1-trifluoromethanesulfonylpiperidin-4-yl) ethane-1-yl] -3H-1,
4,8b-Triazaacenaphthylene, 4,5-dihydro-
4- [3- (1-trifluoromethanesulfonylpiperidin-4-yl) propan-1-yl] -3H-1,4,
8b-Triazaacenaphthylene-3-one, 1,2-dihydro-3-methyl-1- [3- (1-trifluoromethanesulfonylpiperidin-4-yl) propane-1-
Yl] -1,4.7b-triazacyclopent [cd] inden-2-one, 4,5-dihydro-4- [2- (1-
Trifluoromethanesulfonylpiperidin-4-yl)
Ethane-1-yl] -3H-1,4,8b-triazaacenaphthylene-3,5-dione, 4,5-dihydro-2-methyl-4- [2- (1-trifluoromethanesulfonylpiperidine- 4-yl) ethane-1-yl] -3H-
1,4,8b-Triazaacenaphthylene-3,5-dione, 4,5-dihydro-2-methyl-4- [2- (1-
Trifluoromethanesulfonylpiperidin-4-yl)
Ethane-1-yl] -3H-1,4,8b-triazaacenaphthylene, 4,5-dihydro-2-methyl-4- [2
-(1-trifluoromethanesulfonylpiperidine-4
-Yl) ethane-1-yl] -3H-1,4,8b-triazaacenaphthylene-3-one, 4,5-dihydro-2
-Methyl-4- [2- (1-trifluoromethanesulfonylpiperidin-4-yl) ethan-1-yl] -3H
-1,4,8b-Triazaacenaphthylene-5-one or a salt thereof and the like.

Compound (I) obtained by the method of the present invention is
A salt may be formed, and a physiologically acceptable acid addition salt is particularly preferable. As the salt of the compound of the present invention,
For example, inorganic acid salts (eg, hydrochloride, phosphate, hydrobromide, sulfate, etc.), organic acid salts (eg, acetate, formate, propionate, fumarate, maleate, succinate) Acid, tartrate, citrate, malate, oxalate,
Benzoate, methanesulfonate, benzenesulfonate, etc.) are used. When the compound (I) has an acidic group such as a carboxyl group, the salt of the compound (I) may be, for example, an inorganic base salt (eg, an alkali metal salt such as a sodium salt or a potassium salt, a calcium salt,
An alkaline earth metal salt such as a magnesium salt, an aluminum salt, an ammonium salt, or the like, or an organic base salt (for example, a trimethylamine salt, a triethylamine salt, or the like) is used. Compound (I) may be a hydrate or a non-hydrate. The compound (I) or a salt thereof may have an asymmetric carbon in the molecule, but when two kinds of stereoisomers of R-coordination or S-coordination exist, each of them or a mixture thereof is used. Included in the present invention.

Compound (II) or a salt thereof and compound (II)
In the reaction with I) or a salt thereof, 1 equivalent to a large excess (about 1 to 10 equivalents) of compound (III) is used based on compound (II). As the solvent used, for example, water,
Lower alcohols (eg, methanol, ethanol,
Ketones (eg, acetone, methyl ethyl ketone, etc.), ethers (eg, tetrahydrofuran, etc.), aprotic polar solvents (eg,
N, N-dimethylformamide, acetonitrile, dimethylsulfoxide, and the like). When this reaction is performed in the presence of a base, the reaction is efficiently performed. Examples of the base include basic compounds such as sodium hydroxide, potassium hydroxide, sodium hydride, potassium carbonate, triethylamine, diisopropylethylamine, and 1,8-diazabicyclo [5.4.0] -7-undecene. Can be The base is preferably used in an amount of about 1 to 10 equivalents. In the reaction, 1 equivalent to a large excess (1 to 10 equivalents) of sodium iodide may be added as a reaction accelerator. The reaction temperature can be from about -20 to 200 ° C. The reaction time is generally about 10 minutes to 24 hours, preferably about 0.5 to 6 hours.

Compound (I) obtained by the above reaction
Can be converted into a salt by a method known per se or a method analogous thereto (for example, neutralization, etc.), and conversely, when it is obtained as a salt, It can be converted to a free form or another salt by a method according to this. The compound (I) or a salt thereof thus obtained can be isolated and purified by usual separation means such as, for example, phase transfer, concentration, solvent extraction, fractionation, crystallization, recrystallization, distillation, chromatography and the like. . When compound (I) or a salt thereof exists as a diastereomer, a conformer, or the like, each can be isolated by a usual separation and purification means, if desired. When the compound (I) or a salt thereof is in a racemic form, it can be separated into a d-form and a 1-form by ordinary optical resolution means.

The starting compounds (II) and (III) used in the method of the present invention can be produced by the following production methods. Compound (II) used in the method of the present invention
Is, for example, the Journal of Heterocyclic
Chemistry (Journal of Heterocyclic Chemistry),
Vol. 9, p. 81 (1972), JP-A-8-81467
Can be produced by the method described in Japanese Patent Application Laid-Open (JP-A-PCT WO96 / 02542).

In producing compound (III), a sulfonylating agent containing a hydrocarbon group which may have a substituent is allowed to act on compound (IV). As the “hydrocarbon group which may have a substituent” contained in the sulfonylating agent, the same as the “hydrocarbon group which may have a substituent” represented by R described above is used. Examples of the sulfonylating agent include a trifluoromethanesulfonylating agent (eg, trifluoromethanesulfonic anhydride, trifluoromethanesulfonyl chloride, N-phenyltrifluoromethanesulfonimide, etc.), an alkyl sulfonylating agent (eg, methanesulfonyl chloride, etc.) ), Aromatic sulfonylating agents (eg, benzenesulfonyl chloride, p
-Toluenesulfonyl chloride) and the like.
The amount of the sulfonylating agent used is 1 to an excess, preferably about 1 to 5 equivalents. Examples of the solvent used in the reaction include halogenated hydrocarbons (eg, methylene chloride,
Chloroform, dichloroethane, etc.), ethers (eg,
Diether ether, tetrahydrofuran, etc.), esters (eg, methyl acetate, ethyl acetate, etc.), aprotic solvents (eg, acetonitrile, acetone, dimethyl sulfoxide, etc.), and aromatics (eg, benzene, toluene, etc.). . At the time of the reaction, a base may be used. As the base used at this time, for example, an inorganic base (eg, potassium carbonate, sodium carbonate, etc.), an organic base (eg, triethylamine, tributylamine, etc.), an alcoholate (eg,
Sodium methylate, sodium ethylate, etc.). The reaction temperature is about -80 to 100C, preferably about -30 to 50C. The reaction time is usually about 1
0 minutes to 24 hours, preferably about 1 minute to 10 hours. Compound (II), Compound (III) and Compound (I
Each of V) may be a salt, and examples of such a salt include those similar to the salt of compound (I) described above.

The compound (I) or a salt thereof obtained by the method of the present invention has excellent PDGF inhibitory activity, renal disease ameliorating activity, lipid lowering activity, etc., and is low toxic, and is therefore useful in mammals (for example, Mice, rats, hamsters,
Rabbits, cats, dogs, cows, horses, sheep, monkeys, humans, etc.)
Acute renal failure, diabetic nephropathy, nephritis (e.g., mesangial cell proliferative glomerulonephritis, endoproliferative glomerulonephritis, membrane proliferative glomeruloneitis I, II, III, crescentic glomerulonephritis Chronic and acute glomerulonephritis such as proliferative glomerulonephritis, sclerosing glomerulonephritis, etc.), prophylactic / therapeutic agents for arteriosclerotic diseases, preventive agents for reocclusion after PTCA (percutaneous coronary angioplasty), It can be used safely as a drug for preventing or treating rheumatoid arthritis, a drug for preventing or treating cancer, or a drug for preventing or treating hyperlipidemia.

The compound (I) or a salt thereof may be in bulk, but is usually a carrier for pharmaceutical preparations such as excipients (eg, calcium carbonate, kaolin, sodium hydrogencarbonate, lactose, soluble starch, corn starch, Crystalline cellulose, talc, granulated sugar, porous substances, etc.), binders (eg, dextrin, gums, pregelatinized starch, gelatin, hydroxypropylcellulose, hydroxypropylmethylcellulose, pullulan, etc.), thickeners (eg, natural gums) , Disintegrants (eg, carboxymethylcellulose calcium, croscarmellose sodium, crospopidone,
Low-substituted hydroxypropylcellulose, partially pregelatinized starch, etc.), solvents (eg, water for injection, physiological saline,
Ringer's solution, alcohol, propylene glycol, sesame oil, corn oil, etc.), dispersants (eg, Tween 80, HCO60, carboxymethylcellulose, sodium alginate, etc.), suspending agents (eg, sodium lauryl sulfate, benzalkonium chloride, etc.), Dissolution aids (eg, polyethylene glycol, propylene glycol, D-mannitol, benzyl benzoate, ethanol, trisaminomethane, triethanolamine,
Sodium carbonate, sodium citrate, etc.), soothing agents (eg, benzyl alcohol), buffers (eg, phosphate, acetate, carbonate, citrate, etc.), lubricants (eg, magnesium stearate) , Calcium stearate, talc, starch, sodium benzoate, etc.), coloring agents (eg, tar pigment, caramel, iron sesquioxide, titanium oxide, riboflavins, etc.), flavoring agents (eg, sweets, flavors, etc.), stabilization Agents (eg, sodium sulfite, ascorbic acid, etc.) and preservatives (eg, parabens, sorbic acid, etc.)
It is prepared according to a conventional method using an appropriate amount.

The pharmaceutical preparation, which may contain the carrier for a pharmaceutical preparation, suitably contains an effective amount of the compound (I) or a salt thereof for preventing or treating the above-mentioned disease. The content of the compound (I) or a salt thereof in the pharmaceutical preparation is usually
It is about 0.1 to 100% by weight of the whole pharmaceutical preparation. Further, the pharmaceutical preparation may contain other pharmaceutical ingredients other than the compound (I) or a salt thereof as an active ingredient, and these ingredients are not particularly limited as long as the purpose as a medicine is achieved, and may be appropriately determined. It can be used at a proper mixing ratio. Other pharmaceutical ingredients other than compound (I) or a salt thereof include, for example, diuretics, angiotensin II receptor antagonists,
Calcium antagonist, angiotensin converting enzyme (AC
E) Inhibitors, chymase inhibitors, anti-inflammatory agents, hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitors, squalene synthase inhibitors and the like.

Specific examples of dosage forms include tablets (including sugar-coated tablets and film-coated tablets), pills, capsules, granules, fine granules, powders, syrups, emulsions, suspensions, injections, Suppositories and the like are used. These pharmaceutical preparations are prepared according to a conventional method (for example, a method described in the Japanese Pharmacopoeia). The main production methods of pharmaceutical preparations are shown below, but are not limited thereto. (1) Tablet Compound (I) or a salt thereof as it is, or an excipient,
A binder, disintegrant or other suitable carrier for a pharmaceutical preparation is added and uniformly mixed, granulated by an appropriate method, and then a lubricant and the like are added, followed by compression molding. Then
If necessary, the skin may be coated with a suitable coating agent for the purpose of taste masking, enteric coating or persistence. (2) Injection A certain amount of compound (I) or a salt thereof is dissolved and suspended in water for injection or the like, if necessary, by adding a stabilizer, a solubilizing agent, a suspending agent, a buffer, a preservative, and the like. Alternatively, the mixture is emulsified to a fixed dose, or a fixed amount of the compound (I) of the present invention or a salt thereof is taken and sealed in a container for injection. (3) Capsule The compound (I) or a salt thereof and a carrier for pharmaceutical preparations such as a suitable excipient are uniformly mixed, or granulated by an appropriate method, or a suitable coating on the granulated material. The capsules coated with the agent are filled directly or lightly into capsules.

The pharmaceutical preparation obtained in this way is PD
Since it has a GF inhibitory action, a renal disease improving action, a lipid lowering action, etc., and is low in toxicity and safe, it is useful as a medicament for preventing and treating diseases based on these pharmacological actions. That is, the pharmaceutical preparation of the present invention thus obtained includes, for example, acute renal failure, diabetic nephropathy, nephritis (eg, proliferative glomerulonephritis such as mesangial cell proliferative glomerulonephritis, sclerosing glomerulonephritis, etc. ), Arteriosclerosis, PTC
It can be used for prevention and / or treatment of reocclusion after A, rheumatoid arthritis, cancer, hyperlipidemia and the like. The dose of the pharmaceutical preparation varies depending on the administration route, symptoms, age and weight of the patient. For example, when administered orally to an adult patient with diabetic nephropathy, compound (I) or a salt thereof is used. About 0.05 to 50 mg / kg, preferably about 0.1 to 30 mg / kg per day as an active ingredient
It is preferable to administer the drug in 1 to 3 divided doses (for example, 1 to 3 times). The route of administration of the pharmaceutical preparation is not particularly limited by various circumstances, but for example, it can be administered orally or parenterally. "Parenteral" as used herein includes intravenous, intramuscular, subcutaneous, intranasal, rectal, vaginal and intraperitoneal administration.

[0031]

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, the present invention will be described in more detail with reference to Reference Examples and Examples, but the present invention is not limited thereto. The abbreviations in Reference Examples and Examples have the following meanings. s: singlet, d: doublet, t: triplet,
q: quartet, dd: double doublet, m: multiplet, br: wide, J: coupling constant.

[0032]

【Example】

Reference Example 1 Production of 4- (2-chloroethane-1-yl) piperidine hydrochloride: A solution of 4-piperidineethanol (310 g) in tetrahydrofuran (3.1 L) was ice-cooled, and thionyl chloride (511 g) was added dropwise thereto. did. The mixture was heated and stirred under reflux for 3 hours. The reaction solution was cooled on ice and the precipitated crystals were collected by filtration. The crystals were washed with tetrahydrofuran (1 L) and then dried to obtain 321 g of 4- (2-chloroethane-1-yl) piperidine hydrochloride (yield 90%). ¹ H-NMR (CDCl ₃ , δ, 300 MHz): 1.63-1.93 (m, 7H), 2.85-
2.93 (m, 2H), 3.49-3.53 (m, 2H), 3.85 (t, J = 6.3Hz, 2H),
9.39-9.58 (m, 2H).

Example 1 Preparation of 4- (2-chloroethane-1-yl) -1-trifluoromethanesulfonylpiperidine: 4- (2-chloroethane-1-yl) piperidine hydrochloride (311 g) in toluene (3. 1 L) The suspension was cooled to −30 ° C., and trifluoromethanesulfonic anhydride (710 g) was added dropwise thereto while maintaining the temperature, followed by dropwise addition of triethylamine (514 g). The reaction was brought to 0-5 ° C and stirred for 4 hours. Water (760 ml) was added to the reaction solution, and the mixture was separated and washed with water (760 ml). The organic layer was dried over anhydrous sodium sulfate and concentrated. The obtained oil was purified by a silica gel column to obtain 336 g of a crude oil. The crude oil was distilled under reduced pressure to give 4- (2-chloroethane-1-yl)-.
293 g of 1-trifluoromethanesulfonylpiperidine
(50% yield). ¹ H-NMR (CDCl ₃ , δ, 300 MHz): 1.25-1.36 (m, 2H), 1.74-
1.85 (m, 5H), 3.00-3.07 (m, 2H), 3.59 (t, J = 6.3Hz, 2H),
3.93-4.00 (m, 2H).

Example 2 1,2-Dihydro-1- [2- (trifluoromethanesulfonylpiperidin-4-yl) ethane-1-yl] -1,
4,7b-Triazacyclopent [cd] indene-2-
Preparation of ON: 1,2-dihydro-1,4.7b-triazacyclopento [cd] inden-2-one (5.3 g) and 4- (2-chloroethane-1-yl) -1-trifluoromethane To a suspension of sulfonylpiperidine (5.3 g) in N, N-dimethylformamide (53 ml) was added 1,8-diazabicyclo [5.4.0] -7-undecene (9.7 g) at 80 ° C. for 3 hours. Stirred. The reaction solution was cooled on ice and the precipitated crystals were collected by filtration. The crystals were treated with 20% aqueous methanol (50
ml), dried and dried in 1,2-dihydro-1- [2-
(Trifluoromethanesulfonylpiperidin-4-yl)
Ethan-1-yl] -1,4,7b-triazacyclopento [cd] inden-2-one 10.8 g (81% yield)
I got ¹ H-NMR (CDCl ₃ , δ, 300 MHz): 1.35-1.45 (m, 2H), 1.54-
1.59 (m, 1H), 1.83-1.99 (m, 4H), 2.96-3.05 (m, 2H), 3.95
-3.99 (m, 2H), 4.15 (t, J = 7.0Hz, 2H), 6.85 (d, J = 7.0Hz, 1
H), 7.67 (d, J = 8.6Hz, 1H), 7.78 (dd, J = 7.0,8.6Hz, 1H),
8.36 (s, 1H).

[0035]

According to the method of the present invention, a tricyclic compound having excellent pharmacological action can be obtained in a high yield with a small number of steps and without using many expensive raw materials.

Claims (14)

[Claims] 1. A compound of the general formula (II) [In the formula, ring A may have a substituent, ring B may have one oxo group, and R ¹ may have a hydrogen atom, a halogen atom, and a substituent. Shows a hydrocarbon group or an acyl group. And a salt thereof and a compound represented by the general formula (III): [Wherein, Z is a leaving group, X is a divalent hydrocarbon group which may have a substituent, and Y ring is a nitrogen-containing 5- or 6-membered heterocyclic ring which may have a substituent. And R represents a hydrocarbon group which may have a substituent. And a salt thereof represented by the general formula (I): [The symbols in the formula are as defined above. Or a salt thereof. 2. The ring A is halogen, C _1-6 alkyl, halogeno-C _1-6 alkyl, C _1-6 alkoxy, halogeno-C
_1-6 alkoxy, C _1-6 alkylthio, halogeno-C _1-6
Alkylthio, hydroxy, carboxy, cyano, nitro, amino, mono- or di-C _1-6 alkylamino,
Formyl, mercapto, C _1-6 alkyl-carbonyl,
C _1-6 alkoxy-carbonyl, sulfo, C _1-6 alkylsulfonyl, carbamoyl and mono- or di-C
Ring B may be substituted with 1 to 3 groups selected from _1-6 alkyl-carbamoyl; A ring represented by the formula: wherein X is (1) a C _1-15 alkylene group, a C _2-16 alkenylene group or a C _2-16 alkynylene group which may be substituted by 1 to 5 C _1-6 alkyl or phenyl groups. , (2) halogen, C _1-6 alkyl, C _1-6 alkoxy, C _1-6 alkylthio, hydroxy, carboxy, cyano, nitro, amino, mono- or di-C _1-6 alkylamino, formyl, mercapto, Substituted with 1 to 4 groups selected from C _1-6 alkyl-carbonyl, C _1-6 alkoxy-carbonyl, sulfo, C _1-6 alkylsulfonyl, carbamoyl and mono- or di-C _1-6 alkyl-carbamoyl. An optionally substituted phenylene group or (3) a divalent group formed by combining these groups, wherein the Y ring is halogen, C _1-6 alkyl, halogeno-C _1-6 alkyl, C _1-6 alkoxy, Haloge -C _1-6 alkoxy,
C _1-6 alkylthio, halogeno-C _1-6 alkylthio, hydroxy, carboxy, cyano, nitro, amino, mono- or di-C _1-6 alkylamino, formyl, mercapto, C _1-6 alkyl-carbonyl, C _{1 -6} alkoxy-
Piperidine, pyrrolidine or pyridine optionally substituted with 1 to 3 groups selected from carbonyl, sulfo, C _1-6 alkylsulfonyl, carbamoyl and mono- or di-C _1-6 alkyl-carbamoyl, , Hydroxy, cyano, carbamoyl, mono- or di-C _1-6 alkyl-carbamoyl, carboxy, C _1-6 alkoxy-carbonyl, sulfo, halogen, C _1-6 alkoxy, phenoxy, halogeno-phenoxy, C _{1-6 Alkylthio} , mercapto, phenylthio, pyridylthio, C _1-6 alkylsulfinyl, C _1-6
Selected from alkylsulfonyl, amino, C _1-6 acylamino, mono- or di-C _1-6 alkylamino, 4- to 6-membered cyclic amino group, C _1-7 acyl, benzoyl, nitrogen atom, sulfur atom and oxygen atom 5- or 6-membered monocyclic aromatic heterocyclic group having 1 to 4 heteroatoms and 5- or 6-membered aromatic heterocycle having 1 or 2 heteroatoms selected from nitrogen, sulfur and oxygen A C _1-15 alkyl group, a C _3-8 cycloalkyl group which may be substituted with 1 to 5 groups selected from a bicyclic aromatic heterocyclic group formed by condensation of C
_{A 2-18} alkenyl group, a C _7-16 aralkyl group or a C _6-14 aryl group, and a C _7-16 aralkyl group or a C _6-14 aryl group may be a C _1-6 alkyl group, a halogeno —C _1-6 alkyl or oxo; R ¹ is (1) a hydrogen atom, (2) a halogen atom, (3) an acyl group derived from a carboxylic acid, or (4) nitro, hydroxy, , Cyano, carbamoyl, mono- or di-C _1-6 alkyl-carbamoyl, carboxy, C _1-6 alkoxy-carbonyl, sulfo, halogen, C _1-6 alkoxy, phenoxy, halogeno-phenoxy, C _1-6 alkylthio, Mercapto, phenylthio, pyridylthio, C _1-6 alkylsulfinyl, C _1-6 alkylsulfonyl, amino,
1 to 4 hetero atoms selected from C _1-6 acylamino, mono- or di-C _1-6 alkylamino, 4- to 6-membered cyclic amino, C _1-7 acyl, benzoyl, nitrogen atom, sulfur atom and oxygen atom A 5- or 6-membered monocyclic aromatic heterocyclic group having an atom and a 5- or 6-membered aromatic heterocyclic ring having one or two heteroatoms selected from nitrogen, sulfur and oxygen atoms condensed with a benzene ring Selected from a bicyclic aromatic heterocyclic group formed by
A C _1-15 alkyl group, a C _3-8 cycloalkyl group, a C _2-18 alkenyl group, a C
_{A 7-16} aralkyl group or a C _6-14 aryl group; and a C _7-16 aralkyl group or a C _6-14 aryl group, in addition to these substituents, a C _1-6 alkyl group, a halogeno-C _1-6 alkyl group Or the oxo group, wherein Z is a halogen atom, a C _1-4 alkylsulfonyloxy group or a C _6-10 arylsulfonyloxy group. (3) ring A is unsubstituted and ring B is of the formula Wherein R ¹ is a hydrogen atom or a C _1-6 alkyl group, X is a C _1-6 alkylene group, Y ring is piperidine and R is a halogeno-C _1-6 alkyl group. Law. 4. The ring A may be substituted with a group selected from halogen, C _1-6 alkyl, C _1-4 alkylthio, C _1-4 alkoxy, hydroxy, carboxy, nitro and amino, wherein R ¹ is (1) a hydrogen atom, (2) a C _1-10 alkyl group or a C _6-14 aryl group each of which may be substituted with a group selected from halogen, hydroxy, carboxy, nitro and amino, (3) C _{1- 6} alkoxy-carbonyl group or (4) C _1-6 alkanoyl group, Z is a halogen atom, C _1-4 alkylsulfonyloxy group or C _6-10 arylsulfonyloxy group, X is halogen, hydroxy, C _{1- A} C _1-6 alkylene group which may be substituted with a group selected from ₄ alkyl and a C _6-14 aryl group, a Y ring having a nitrogen-containing 6-membered heterocyclic ring, and R is (i) halogen, (ii) cyano, (iii) hydroxy, (iv) halogen Optionally substituted C _1-6 alkyl, (v) C _1-4 alkoxy optionally substituted with halogen, (vi) C _6-14 aryl, (vii) optionally esterified carboxy and (viii) a C _1-15 alkyl group, a C _3-8 cycloalkyl group, a C _2-10 alkenyl group, a C _6-14 aryl group each of which may be substituted with a group selected from a 5- or 6-membered heterocyclic group Or C
_The method according to claim 1, which is a _7-16 aralkyl group. 5. The ring A may be substituted with a group selected from halogen and C _1-4 alkyl, and the ring B may have the formula: Wherein R ¹ is a hydrogen atom, a C _1-6 alkyl group or a C _6-14 aryl group, and X is a C _1- optionally substituted with a group selected from halogen, hydroxy and C _1-4 alkyl. _{A 6-} alkylene group, the Y ring is a nitrogen-containing 6-membered heterocyclic ring, and R is a C _1-10 alkyl group _optionally substituted with a group selected from halogen, hydroxy and optionally esterified carboxy. Item 10. The production method according to Item 1. (6) ring A is unsubstituted and ring B is of the formula The method according to claim ¹ , wherein R ¹ is a hydrogen atom, Y ring is a nitrogen-containing 6-membered heterocyclic ring, and R is halogen-substituted C _1-6 alkyl group. (7) ring A is unsubstituted and ring B is of the formula The method according to claim ¹ , wherein R ¹ is a hydrogen atom, Z is a chlorine atom, X is an ethylene group, Y ring is piperidine, and R is a trifluoromethyl group. 8. The method according to claim 1, which is carried out in the presence of a base. 9. A compound of the general formula [Wherein, Z is a leaving group, X is a divalent hydrocarbon group which may have a substituent, and Y ring is a nitrogen-containing 5- or 6-membered heterocyclic ring which may have a substituent. And R represents a hydrocarbon group which may have a substituent. Or a salt thereof. 10. X is (1) a C _1-15 alkylene group, a C _2-16 alkenylene group or a C _2-16 alkynylene group which may be substituted by 1 to 5 C _1-6 alkyl or phenyl, (2) halogen, C _1-6 alkyl, C _1-6 alkoxy,
C _1-6 alkylthio, hydroxy, carboxy, cyano, nitro, amino, mono- or di-C _1-6 alkylamino, formyl, mercapto, C _1-6 alkyl-carbonyl, C _1-6 alkoxy-carbonyl, sulfo, C _1-6
A phenylene group which may be substituted with 1 to 4 groups selected from alkylsulfonyl, carbamoyl and mono- or di-C _1-6 alkyl-carbamoyl, or (3) a divalent group formed by combining these groups Wherein the Y ring is halogen, C _1-6 alkyl, halogeno-C _1-6 alkyl, C _1-6 alkoxy, halogeno-C _1-6 alkoxy,
C _1-6 alkylthio, halogeno-C _1-6 alkylthio, hydroxy, carboxy, cyano, nitro, amino, mono- or di-C _1-6 alkylamino, formyl, mercapto, C _1-6 alkyl-carbonyl, C _{1 -6} alkoxy-
Piperidine, pyrrolidine or pyridine optionally substituted with 1 to 3 groups selected from carbonyl, sulfo, C _1-6 alkylsulfonyl, carbamoyl and mono- or di-C _1-6 alkyl-carbamoyl, , Hydroxy, cyano, carbamoyl, mono- or di-C _1-6 alkyl-carbamoyl, carboxy, C _1-6 alkoxy-carbonyl, sulfo, halogen, C _1-6 alkoxy, phenoxy, halogeno-phenoxy, C _{1-6 Alkylthio} , mercapto, phenylthio, pyridylthio, C _1-6 alkylsulfinyl, C _1-6
Alkyl sulfonyl, amino, C _1-6 acylamino, mono- or di-C _1-6 alkylamino, 4- to 6-membered cyclic amino, C _1-7 acyl, benzoyl, nitrogen atom, sulfur atom and oxygen atom A 5- or 6-membered monocyclic aromatic heterocyclic group having from 4 to 4 heteroatoms and a 5- or 6-membered aromatic heterocycle having 1 or 2 heteroatoms selected from nitrogen, sulfur and oxygen A C _1-15 alkyl group, a C _3-8 cycloalkyl group, a C _3-8 cycloalkyl group which may be substituted with 1 to 5 groups selected from a bicyclic aromatic heterocyclic group formed by condensation with a benzene ring;
_{A 2-18} alkenyl group, a C _7-16 aralkyl group or a C _6-14 aryl group, and a C _7-16 aralkyl group or a C _6-14 aryl group may be a C _1-6 alkyl group, a halogeno The compound according to claim 9, which may be substituted with a _-C1-6 alkyl group or an oxo group, and wherein Z is a halogen atom, a _C1-4 alkylsulfonyloxy group or a _C6-10 arylsulfonyloxy group. 11. The compound according to claim 9, wherein X is a C _1-6 alkylene group, Y ring is piperidine and R is a halogeno-C _1-6 alkyl group. 12. The compound according to claim 9, wherein X is an ethylene group, Y ring is piperidine and R is a trifluoromethyl group. 13. A compound of the general formula (IV) [In the formula, Z represents a leaving group, X represents a divalent hydrocarbon group which may have a substituent, and Y ring represents a nitrogen-containing 5- or 6-membered heterocyclic group. Wherein a sulfonylating agent containing a hydrocarbon group which may have a substituent is allowed to act on the compound represented by the general formula (III) or a salt thereof. [Wherein, R represents a hydrocarbon group which may have a substituent,
And other symbols have the same meanings as defined above). 14. Use of a compound represented by the formula (III) or a salt thereof for producing a compound represented by the formula (I) or a salt thereof.