JPS62209062A - 2-pyridylmethylthio-or 2-pyridylmethylsulfinyl-substituted condensed ring compound - Google Patents

Abstract

NEW MATERIAL:A compound expressed by formula I [A, B, D, E and F are C or N; R<1> and R<2> are H, lower alkyl, lower alkoxy, nitro or lower alkyl substituted by a halogen; amino which may be substituted by OH, lower alkanoyl or toluenesulfonyl; R<3>-R<5> are H, lower alkyl, lower alkoxy or adjacent two groups together form a group expressed by formula IV (R<6> is H or lower alkyl), n is 0 or 1] or salt thereof. EXAMPLE:2-{[(3,5-Dimethyl-4-methoxy-2-pyridyl)methyl]thio}quinoline. USE:A medicine, preventing agent and remedy for gastropathy, e.g. gastric acid secretion inhibitor, preventive agent and remedy for gastric ulcer, etc. PREPARATION:A condensed ring thiol expressed by formula II is reacted with a 2-halogenomethylpyridine expressed by formula III (X is halogen) in the presence of a base to give the compound expressed by formula I (n is 0), which is then oxidized with an oxidizing agent to afford the compound expressed by formula I (n is 1).

Description

Detailed Description of the Invention (Industrial Field of Application) The present invention relates to pyridylmethylthio (or sulfinyl) expressed by the following general formula, which is useful as a preventive or therapeutic agent for gastric diseases.
The present invention relates to group-substituted fused ring compounds or pharmaceutically acceptable salts thereof.

(In the formula, A, B, D, E and F are carbon atoms or nitrogen atoms.

R1 and R2 are hydrogen atoms, lower alkyl a, low R alkoxy groups, and nitro groups.

A lower alkyl group substituted with a halogen atom, a hydroxyl group, a lower alkanoyl group, a lower alkanoyl group, a lower alkanoyl group, an amino group R3, R4, and R5, which may be substituted with a halogen atom, are a hydrogen atom, a lower alkyl group, a lower alkoxy group, or an adjacent Formed by two groups taken together - or alternatively refers to a hydrogen atom or a lower alkyl group. ) is the group h ! 10 Li Ding = +sL Each means Junko. ) (Prior Art) Fused ring compounds substituted with pyridylmethylthio (or sulfinyl) groups have been previously described in Japanese Patent Publication No. 59-24157 and Japanese Patent Publication No. 60-34956. The compound of the present invention is a novel compound that differs in the type of condensed ring from these known compounds.

(Means for Solving the Invention) The compound represented by the general formula (1) will be further explained as follows.

The fused ring in general formula CI) is a fused two-ring compound which may contain nitrogen and 1 to 5 atoms. The main types of these condensed rings are as follows.

Naphthalene ring, quinoline ring, inquinoline ring.

Quinogisaline ring, phthalazine ring, quinazoline ring, ■, 8
- Naphthyridine ring, pteridine ring.

The compounds of the present invention have a 2-pyridylmethylthio group or a 2-
Substituted with a pyridylmethylsulfinyl group. here K
"Lower alkyl group" meant by R3, R' and R5
is a linear or branched alkyl group having 1 to 5 carbon atoms, such as a methyl group, ethyl group, propyl group, isopropyl group, butyl group, and "lower alkoxy group" is a methoxy group, ethoxy group, Propoxy group.

Examples include impropoxy group, butoxy group, and blue-butoxy group. Also, a group where two adjacent groups meet together (
In the formula, R6 is the same or different and means a hydrogen atom or a lower alkyl group. )as.

A group represented by the formula (-CH, OCR, O- and its mono-Cf (.

or di-lower alkyl substituents (e.g. -CH201:
Ho-.

When it is 0, it is a 2-pyridylmethylthio group.

When n is 1, it is a 2-pyridylmethylsulfinyl group.

The above condensed ring may be substituted with a group represented by RI or R2 in addition to the 2-pyridylmethylthio (or sulfinyl) group. The meaning of R1 or R2 is as mentioned above, but to further explain the middle part,
The "lower alkyl group" and the "lower alkoxy group" are the same as those explained for R3, R4 and R'K above.

"Lower alkyl group substituted with a halogen atom" refers to a lower alkyl group having 1 to 4 halogen atoms (for example, ), elementary atom, chlorine atom, bromine atom, etc.), [lower alkanoyl group] "or an amino group which may be substituted with a toluenesulfonyl group" is an amino group.

Examples include an acetylamino group, a propionylamino group, a butyrylamino group, and a p-1 luenesulfonylamino group.

One or two of these groups R1 and R2 can be substituted at any carbon atom position in the condensed ring.

Next, as a salt of the compound of general formula (I).

It is a pharmaceutically acceptable salt with an inorganic or organic acid. Such acids include, for example.

Hydrohalic acids (hydrochloric acid, hydrobromic acid, etc.).

Inorganic acids such as sulfuric acid, nitric acid, phosphoric acid, sulfonic acid and formic acid, acetic acid, propionic acid, lactic acid, tartaric acid.

Examples include organic acids such as citric acid, maleic acid, methanesulfonic acid, and toluenesulfonic acid.

(Manufacturing method) The compound of the present invention is manufactured by the method shown by the following reaction formula.

(In the formula, X means a halogen atom.) This method:
First, a condensed ring thiol represented by the formula (II) and (III)
A fused ring compound (Ia) substituted with a 2-pyridylmethylthio group is produced by reacting with 2-halogenomethylpyridine represented by the formula (first step), and then this compound (Ia) is treated with an oxidizing agent. The corresponding sulfinyl form (
Ib) (second step).

The first step is a method for producing the target compound (Ia) in which n is 0 in the compound of general formula (I), and the second step is a method for producing the target compound (Ib) in which n is 1.

To carry out the reaction in the first step, corresponding amounts of fused ring thiol (n) or its salt and 2-halogenomethylpyridine (m) or its salt are reacted in the presence of a base. Examples of the base used here include inorganic bases such as sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, and sodium bicarbonate, and organic bases such as triethylamine. The appropriate amount of base to be added is 3 molar equivalents when both (n) and (TIT) are used as acid salts, and 2 molar equivalents when the educt of (■) and the salt of (II) are used. This reaction is usually carried out in a solvent at room temperature or at elevated temperatures. As the solvent, alcohols such as methanol and ethanol, water, chloroform, dimethyl sulfoxide, benzene, ether, etc. are used.

The reaction product is obtained as a free base or as its acid addition salt, depending on the raw materials used and reaction conditions.

In the second step, the fused ring compound (Ia) or a salt thereof is treated with an oxidizing agent to obtain the corresponding sulfinyl compound. When using the salt of (Ia), it is first neutralized to form a free form of (Ia) and then treated with an oxidizing agent.

Metachloroperbenzoic acid (MCPBA) is used as an oxidizing agent.
In addition, peracetic acid, hydrogen peroxide, peracid esters, etc. are used. The oxidation reaction is usually carried out in a solvent under cooling. As the solvent, dichloromethane, chloroform, alcohol, etc. are used.

Target compound (Ia) and (I) obtained by the above production method
When b) is a free base, it can be made into an acid addition salt by reacting it with a pharmaceutically acceptable acid in a conventional manner.

(Effect of the invention) Compound (I) and its salt provided by the present invention are:
It has gastric acid secretion suppressing action and antiulcer action, and is useful as a gastric acid secretion suppressing agent, gastric ulcer preventive and therapeutic agent, and other gastric disease preventive and therapeutic agents.

The gastric acid secretion suppressing effect and anti-ulcer effect of the compounds of the present invention are expressed by the inhibitory activity (IC5o, 50% inhibitory concentration) against H+, ni+-adenosine triphosph 7tase (hereinafter referred to as H'', K''-ATPase) shown below. It was confirmed by
Acta (Biochimica et Biophis)
ica Acta).

728, 31-38 (1983).

The compounds of the present invention can be evaluated by ICS using this pharmacological test method.

was confirmed to be effective at 30 μM or more.

The compound (1) of the present invention and its salts may be used as such or in a known pharmaceutically acceptable carrier.

It is used as a pharmaceutical composition mixed with excipients. Administration is in tablets, capsules, powders, and granules.

It can be administered orally as pills, or parenterally as injections, capsules, ointments, suppositories, etc.

The dosage varies depending on the subject, administration route, symptoms, etc., but it is usually 40 to 400 mg orally per day for adults.
This is administered in divided doses 2 to 4 times a day.

(Example) EXAMPLES The present invention will be explained in more detail by way of examples below.

However, the present invention is not limited to only those described in the examples.

In addition, the main raw material compounds used in the examples will be explained using their production examples as reference examples.

Reference example 1. (Raw material for Example 2) 6-Medoxyquinoline-2-thiol was produced using 2-chloro-6-methoxyquinoline by the method described in Pharmaceutical Journal, Vol. 86, p. 1090, 1966.

Melting point 190-193°C (ethanol) [-f soot vector (m/z) 191 (M”) Reference example 2. (Raw materials for Example 9) (1) Dissolve 15 g of 2-chloroquinoline in 95 g of concentrated sulfuric acid. , 97 g of water-cooled concentrated sulfuric acid and 11 g of nitric acid (70%)
After dropping a mixed acid consisting of the following over 1 hour, the mixture was stirred for 1 hour under water cooling and then for 4 hours at room temperature. The reaction solution was poured into ice water, the precipitated crystalline P was collected, washed with water, and purified by silica gel column chromatography using chloroform-hexane as a developing solvent to obtain 3.7 g of 2-chloro-5-nitroquinoline. Ta.

Mass spectrum: (m/z) 208,210 (
(11) 1.8 g of 2-chloro-5-nitroquinoline and 0.0 g of thiourea in 35 ml of ethanol.
After adding 8 g and refluxing for 2.5 hours, the reaction solution was adjusted to pH 10 using a 20% aqueous solution of caustic soda under water cooling, and then adjusted to pi (7) with acetic acid. One portion of the precipitated crystals was taken, washed with water, and then dissolved in chloroform. Recrystallization from -hexane yielded 1.7 g of 2-mercapto-5-nitroquinoline.

Mass spectrum: (m/z) 206 (M”
) Reference example 3. (Raw material for Example 10) (+) 2.5 g of 2-chloro-8-nitroquinoline
Dissolve it in 90 ml of ethanol and incubate for 10 minutes under nitrogen atmosphere.
After adding 450% palladium on carbon ITlg, hydrogen gas was passed through and stirred. After the reaction is completed, the palladium on carbon is filtered, the solvent is distilled off under reduced pressure, and 50 ml of acetic anhydride is added, followed by stirring at room temperature for 2 hours. After distilling off the solvent under reduced pressure, the residue was purified by silica gel column chromatography using hexane-ethyl acetate as a developing solvent to obtain 1.4 g of 8-acetylamino-2-chloroquinoline.

Mass spectrum: (m/z) 220 CM”
) NMR (δ: CDCl3): 2.36 (3H,
s), 7.26-7.62 (3H, m), 8.08
(IH, d), 8.78 (If(, dd).

9.32 (LH, bs) (fil) 8-acetylamino-2-mercaptoquinoline was obtained in the same manner as in Reference Example 2 (oo) using 8-acetylamino-2-chloroquinoline.

Example 1゜Under nitrogen flow, methanol 15ml 1K sodium hydroxide 0
．． 2-mercaptoquinoline 0
．． 64g was dissolved and then 2-chloromethyl-3,5-
Add 0.89 g of dimethyl-4-methoxypyridine hydrochloride, and stir at room temperature for 1 day. Thereafter, the solvent was distilled off under reduced pressure, and the crystals insoluble in 25 ml of water were collected and recrystallized with methanol (2-[[(3,5- 1.00 g of dimethyl-4-methoxy-2-pyridyl)mercaptoquinoline was obtained.

Elemental analysis value (as CIIIHIllN20S) C(9
19H('1 N(Hata S(Ya calculated value 69.6
5 5.84 9.02 10.33 Measured value 69.
59 6.06 9.05 10.49 Mass spectrum: (m/n) 310 (M”) EI Example 1
The following compounds were obtained in the same manner as above.

Example 2゜2-[[(3,5-dimethyl-4-methoxy-2-pyridyl)methylcothioko-6-methoxyquinoline Melting point 101-102°C (ethyl acetate-ether)
Mass spectrum: (m/z) 340 (M”)
E1 elemental analysis value (as C,.H,,N,OtS)
C(pleasure H(-N(@S(@calculated value 67.03 5.92 8.23 9.42
Measured value 66.94 5.88 8.14 9.40
Example 3. 2-[[(315-dimethyl-4-methoxy-2-pyridyl)methyl]thio]-4-methylquinoline Melting point 129-130°C (ethyl acetate) Mass spectrum: (m/z) 324 (M”) E1 Elemental analysis value (as CnH2gN20S) C (I H
(ml N(9JI 5(11 calculated value 70
．． 34 6.21 8.63 9.88 Measured value
70.17 6,13 8.54 9.95 Example 4゜2-[[(2-pyridyl)methylcothio]quinori7-2
Hydrochloride 8 points 131-135°C (ethanol-ethyl acetate) mass spectrum: (m/z) 252 (M”)
EI elemental analysis value (C,, H,, N, S @ 2HC1
) C(19H(d N(eeS(d cl(
-Calculated value 55.39 4.34 8.61 9.8
6 21.80 Measured value 55.33 4.08 8.
57 9.89 21.52 Example 5°・HCl 8- [[[(3,5-dimethyl-4-methoxy-2-
pyridyl) mercaptoquinoline hydrochloride Melting point 144
~145°C (ethanol) mass spectrum: (m/
z) 311 (M++1) FAB elemental analysis value (as C+gtLaNtO8-HCI)
(@N(@s(transport CI(@calculated value 6)
2.33 5,52 8.08 9.24 10.22
Measured value 62.12 5.45 8.03 9.27
10.36 Example 6゜8-[[(2-pyridyl)methylcothio]quinoline.2
Hydrochloride melting point 116-120°C (ethanol-ethyl acetate) mass spectrum: (rn/z) 252 (M”)
EI elemental analysis value (C15H12N2S ・2HC1-
1,2H20)C(transport H(-N(@S(@calculated value) 51.94 4.71 8.08 9.24
Measured value 51,89 4,47 8.07 9.14
Example 7 4-[[(3,5-dimethyl-4-methoxy-2-pyridyl)methyl]thio]-7-dolifluoromethylquinoline mass spectrum: (m/z) 378 (M”)
NMR (δ: CDC15): 2.25 (3H, s),
2.36 (3H, s).

3.76 (3H, s), 4.46 (2H, s),
7.60-7.72 (2H, m), 8.16-8.3
6 (3H, m), 8.80 (IH, d) Example 8 2-[[(3,5-dimethyl-4-methoxy-2-pyridyl)methyl]thio]-8-nitroquinoline mass spectrum: ( m/z) 355 (M”) NMR (δ, C
DCl, ) 2.22 (3H,s), 2.32 (3H,s),
3.76 (3H, s).

4.78 (2H,s), 7.24~7゜52 (2
H, m), 7.84-8.02 (3H, m), 8
．． 16(IH,s) Example 9 2-[[3,5-dimethyl-4-methoxy-2-pyridyl)methyl]thio]-5-nitroquinoline mass spectrum: (m//Z) 355(M”) NMR (δ, C
DCl,) 2.24 (3H,s)t 2.42 (3H,s),
3.78 (3 to 3).

4.79 (2H,s)t 7.42~7.79(
2H,m) Example 10 8-acetylamino-2-[[(3,5-dimethyl-4
-methoxy-2-pyridyl)methyl]thio]quinoline NMR (δ, CDCl,) 2.20 (3H,s), 2.38 (3H,s), 2.5
4 (3H, s) 3.74 (3H, S), 4.68 (2
H, 8), 1.74-7.50 (3H, m), 7.
82(IH,d)t 8.12(IH,s).

8.74 (IH, dd), 11.18 (IH, bs)
Example 11 2-[(2-naphthylthio)methylcopyridine hydrochloride Melting point 135-141°C (ethanol-ethyl acetate)
Mass spectrum (mHz) 251 (M”) EI elemental analysis value (as C,6H,3NS-IC1)C(
%) H (%) N (%) S (%) C-1 (
%) Calculated value 66.77 4.90 4.87 11.
14 12.32 Measured value 66.53 4.69 4.
83 11.08 12.58 Example 12 0bitio]pteridine Melting point 238-243°C (methanol) Mass spectrum (mHz): 271 (M”) EI elemental analysis value (C
l2H9N50 S) C (%) H (%)
N (%) S (%) Calculated value 53.13 3.34
25.81 11.82 Measured value 53.32 3.
04 25.82 11.67 Example 13 2-[[(3,5-dimethyl-4-methoxy-2-pyridyl)methylcothio-4-hydroxy pteridine Melting point 245-250'C (decomposition) (methanol) mass spectrum (rrv /z) : 329 (M”) E
I elemental analysis value (as CI, H,, IVJSQ, S)
C (%) H (%) N (%) S (%) Calculated value 54.70 4.59 21.26 9.74 Measured value 54.52 4.41 21.44 9.84 Example 14 ・HCl 3 .5-Dimethyl-4-methoxy-2-[(2-naphthylthio)methylcopyridine hydrochloride Melting point 158-160°C (ethanol) Mazuz vector (mHz): 309 (M”) E 1 elemental analysis value (Cl. H,,NO3-as HCl)C (%)
H (%) N (%) S (%) CI (%) Calculated value
65.98 5.83 4.05 9.27 10.
25 Measured value 65.78 5.80 3.89 9.
54 10.05 Example 15 2-[[(3,5-dimethyl-4-methoxy-2-pyridyl)methyl]thio]quinoxaline Melting point 107-109°C (ethanol) Mass spectrum (mHz): 311 (M”) EI elemental analysis value (
CnH17N30 (as S) C (%) H (%)
N (%) S (%) Calculated value 65.57 5.
50 13.49 10.30 Measured value 65.74
5.43 13.44 10.32 Example 16 1-[[(3,5-dimethyl-4-methoxy-2-pyridyl)methylcothiokotalazine Melting point 111-112°C (ethyl acetate) Mass spectrum: (rrL/z) 311 (M”) EI elemental analysis value (C, as Hf7N30 S) C (%)
H (%) N (%) S (%) Calculated value 65.57
5.50 13.49 10.30 Measured value 65.
71 5.56 13.25 10.23 Example 17 2.2.8- )lymethyl-5-[(2-naphthylthio)methy#]-4H-1,3-dioxy[4,5-c copyridine melting point 152-154℃ Mass spectrum (m/Z): 351 (M”) Elemental analysis value (as C21H22NO2SC1) C (%
) H (%) N (%) S (%) CI (%
) Calculated value 65.02 5.72 3.61 8.27
9.14 Actual value 65.26 5.67 3.45
8.16 9.32 Example 18 2.2-dimethyl-8-methyl-5-[(2-quinolylthio)methyl]-4H-1.3-dioxino[4,5-
C Copyridine Melting point 130-132°C Mass spectrum/' (rrV/z): 352 (
M”) Elemental analysis value (as Co to N2 to S) C (%)
H (%) N (%) S (%) Calculated value 68
．． 16 5.72 7.95 9.10 Actual value 68
．． 19 5.70 7.95 8.96 Example 19 2-[[(3,5-dimethyl-
Dissolve 0.34 g of 4-methoxy-2-pyridyl)methylcothioyo6-medoxyquinoline and heat at 0°C under a nitrogen stream.
Add 0.22 g of m-chloroperbenzoic acid and stir for 30 minutes. Thereafter, the 4 reaction mixtures were washed with saturated aqueous sodium bicarbonate solution, and the solvent was distilled off under reduced pressure. By recrystallizing the residue from dichloromethane-ethyl acetate, 2-
[[(3,5-dimethyl-4-methoxy-2-pyridyl)methyl]sulfinyl]-6-medoxyquinoline 0.
25g was obtained.

Melting point 140-144°C (decomposition) Mass spectrum/' (m/z): 356 (M"
) EI elemental analysis value (as C+oHm'zOsS)
C (%) C (%) H (%) S (%) Calculated value
64.02 5.66 7.86 9.00 Measured value
63.87 5.60 7.67 8.82 Example 1
The following compound was obtained in the same manner as in Example 9.

Example 20 2-[[(3,5-dimethyl-4-methoxy-2-pyridyl)methyl]sulfinylcoquinoline Melting point 164
~166°C (dichloromethane-acetonitrile) mass spectrum (rrVz): 326 (M”) E
I elemental analysis value (C+aH+5NzO2S・0.2H
as 2O) C (%) H (%) N (%) S (
%) Calculated value 65.51 5.62 B, 49 9
．． 72 measurement value 65,64 5.45 8.57 9
．． 47 Example 21 2-[[(2-pyridyl)methyl]sulfinyl]quinoline Melting point 110-112°C (acetonitrile-ether) Mass spectrum k (Iv/z): 268 (M
”) EI elemental analysis value (as C+sH+□N2O3) C (%) H (%) N (%) S (%) Calculated value 67.14 4.51 10.44 11.95
Measured value 67.12 4.23 10.48 12.
04 Example 22 8-[[(2-pyridyl)methyl]sulfinyl]quinoline Melting point 122-123°C (dichloromethane-ethyl acetate) Mass spectrum (m/z): 268 (M
”) EI elemental analysis value (Cl5H12N20-0.2
as HtO) C (%) H (%) N (%)
S (%) calculated value 66.25 4.60 10
．． 30 11.79 Measured value 66.28 4.58
10.20 11.74 Run 23 8-[[(3,5-dimethyl-4-methoxy-2-pyridyl)methyl]sulfinylcoquinoline Melting point 154
~155°C (dichloromethane-acetonitrile) mass spectrum” (rrVz): (M”) EI elemental analysis value (as C+aH+aN20tS) C (%)
H (%) N (%) S (%) Calculated value 66.23
5.56 B, 58 9.82 Measured value 66.1
1 5.46 8.55 9.59 Example 24 4-[[(3,5-dimethyl-4-methoxy-2-pyridyl)methylcosulfinyl] -7-) IJ Fluoromethylgynoline Melting point 145-147 ℃ Mass spectrum: (m/z) 394 (M") Elemental analysis value (C+eH+, N2O2"' as Fs)
C (%) H (%) N (%) S (%) F
(%) Calculated value 57.86 4.34 7.10 8.
13 14.45 Actual value 57.80 4.14 6.
88 8.34 14.59 Examples 25 and 26 2-[[(3,5-dimethyl-4-methoxy-2-bipyridyl)methylcothioko 8-nitroquinoline 2.0 g
was suspended in 50ml of ethanol and diluted with 10% under nitrogen atmosphere.
After adding 1.1 g of palladium on carbon, hydrogen gas was passed through the mixture and the mixture was stirred at room temperature. After the reaction is complete, palladium on carbon is filtered,
The residue obtained by distilling off the solvent under reduced pressure was dissolved in 50 mt of pyridine, p-toluenesulfonyl chloride was added under water cooling, and the mixture was stirred for 15 hours.

The solvent was distilled off under reduced pressure, water was added and extracted with chloroform,
Wash with water and dry. After evaporating the solvent under reduced pressure again, the residue was dissolved in 30 m7 of methylene chloride, and 0.8 g of m-chloroperbenzoic acid was added under ice cooling, followed by stirring for 30 minutes. Then add saturated hydrogen carbonate to the reaction solution) 20 ml of IJium aqueous solution
After adding, extract with chloroform, wash with water, dry,
The solvent is removed under reduced pressure. The resulting residue was purified by silica gel column chromatography using chloroform-ethyl acetate as a developing solvent, and recrystallized from chloroform-hexane to obtain the following two target products 02-[
[(3,5-dimethyl-4-methoxy-2-pyridyl)
methylcosulfinyl]-8-(p-toluenesulfonylamino)quinoline (0.65 g) Melting point 147-1
48℃ (decomposition) Mass spectrum/': (rrVZ): 495 (
M'') Elemental analysis value (as CtsH25NsO4St) C (%) H (%) N (%) S (%) Calculated value 60.59 5.08 8.48 12.94 Actual value 60.59 4.92 8. 21 12.66
2-[[(3,5-dimethyl-4-methoxy-2-pyridyl)methylcosulfinyl-5-ethoxy-8-(
p-) luenesulfonylamino) * / IJn (0
, 61g) Melting point 167-168℃ (decomposition) Mass spectrum; (%'Z) 539 (M'') Elemental analysis value <CvrHsNsO5St) C (%)
H (%) N (%) S (%) Calculated value 60.0
9 5.42 7.79 11.88 Actual value 59.
90 5.39 7.75 11.85 Example 27 2-[[(3,5-dimethyl-4-methoxy-2-pyridyl)methyl]sulfinyl]-5-nitroquinoline Melting point 189-191°C Mass spectrum: ( m/Z) 371 (M”) Elemental analysis value (as C+sH+vNsO<S)C (%)
H (%) N (%) S (%) Calculated value 58
．． 21 4.61 11.31 8.63 Actual value 5
8.32 4.47 11.22 8.73 Example 28 8-acetylamino-2-[[(3,5-dimethyl-4
-Methoxy-2-pyridyl)methyl]furfinyl]quinoline Melting point 154-155°C Mass spectrum: (,rrv'Z) 383 (M
”) Elemental analysis value (C20) (as 2+N5OsS)
C (%) H (%) N (%) S (%) Calculated value 62.64 5.52 10.96 8.36 Actual value 62.49 5.40 10.86 8.43 Example 29 3.5 -dimethyl-4-methoxy2-[(2-naphthylsulfinyl)methylcopyridine Melting point 118~
119°C (methylene chloride-ethyl acetate) mass spectrum: (rrL/z) 325 (M”) Et elemental analysis value (C+.H,, N02S・0.3 as H2O) C (%) H (%) N (%) S (%) Calculated value 68.98 5,97 4.23 9.69 Measured value 68.89 5.86 4.07 9.98 Example 30 2-[[(3,5,-dimethyl- 4-Methoxy-2-pyridyl)methyl]sulfinyl]quinoxaline Melting point 1
40-143 (decomposition) (methylene chloride-acetonitrile) Mass spectrum: (m/Z) 327 (M”)
EI elemental analysis value (as C+yH+tNsO2S)C
(%) H (%) N (%) S (%) Calculated value
62.36 5.23 12.83 9.79 Measured value 62.07 5.07 12.63 9.87 Example 31 2.2.8-)dimethyl-5-[(2-quinolylsulfinyl)methylco 4H -1,3-dioxino[4,5
-C]Pyridine Melting point 138-140°C

Claims (1)

[Claims] General formula ▲ Numerical formula, chemical formula, table, etc. ▼ (In the formula, A, B, D, E and F are carbon atoms or nitrogen atoms, R^1 and R^2 are hydrogen atoms, lower Amino groups R^3, R^4 and R^5 which may be substituted with an alkyl group, a lower alkoxy group, a nitro group, a lower alkyl group substituted with a halogen atom, a hydroxyl group, a lower alkanoyl group or a toluenesulfonyl group are Formulas formed by combining a hydrogen atom, a lower alkyl group, a lower alkoxy group, or two adjacent groups▲There are mathematical formulas, chemical formulas, tables, etc.▼(R^ in the formula
6 are the same or different and represent a hydrogen atom or a lower alkyl group. The group n represented by ) means 0 or 1, respectively. ) A 2-pyridylmethylthio (or sulfinyl) substituted fused ring compound or a pharmaceutically acceptable salt thereof.