JPH0625276A - Acylaminosugar derivative and its production - Google Patents

Abstract

PURPOSE:To provide a new acrylaminosuger derivative exhibiting a leukoxytosis action and/or an excellent infection-preventing action, and useful as an infection- preventing agent of an antiinfection-enhancing agent. CONSTITUTION:A derivative of formula I (R<1> is H, heterocyclic group, etc.; X is single bonding hand, alkylene, etc.; R<2> is H, aryl or heterocyclic group which may have a substituent, etc.; Y is alkylene or alkenylene which may have a cycloalkylene at its end, etc.; one of R<3> and R<4> is H, and the other is lower alkoxy, etc.; R<5>, R<6> are H, hydroxy; R<7> is hydroxy and R<8>, R<9> are H, hydroxy; or R<7>, R<8> are combined to each other at their ends of form a lower alkylenedioxy, R<9> is H) and its pharmacologically permissible salt. For example, methyl 6-deoxy-6-[N-octadecanoyl-N-(4-phenylbutyl)amino]-alpha-D-glucopyranos ide. The compound of formula I is obtained e.g. by condensation-reacting a compound of formula II with a compound of the formula: R<2>-Y-COOH in the presence of a dehydrating agent in a solvent preferably at 0-20 deg.C.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a novel acylamino sugar derivative having a protective effect against infection and / or a leukocytosis effect and a method for producing the same.

[0002]

2. Description of the Related Art Among white blood cells, it is known that, especially by enhancing the in vivo function of neutrophils, macrophages and lymphocytes, a bacterial or fungal infection protective effect, an antitumor effect or a wide range of immunological effects are exhibited. ing.

As a compound having such an effect, particularly an infection protective effect, a compound in which an N-acyl-N-alkylamino group is substituted at the 1-position of sugar is known (Japanese Patent Publication No. 1-40036). issue).

On the other hand, Carbohydrate Research (Car
Bohydrate Research), 45 (1975), pp. 65-72 discloses methyl 6-deoxy-2,3-di-O-methyl-6-methylacetamide-α-D-glucopyranoside. No activity is disclosed.

[0005]

DISCLOSURE OF THE INVENTION The present invention provides a novel compound having an equal or superior excellent infection-protecting activity and / or leukocyte-increasing activity as compared with conventionally known acylamino sugar derivatives.

[0006]

The acylamino sugar derivative according to the present invention has the general formula [I]

[0007]

[Chemical 5]

(In the formula, R ¹ is a hydrogen atom or an aryl group or a heterocyclic group which may have a substituent, X is a single bond, an alkylene group, an alkenylene group or an alkynylene group, and R ² is ( 1) hydrogen atom, (2) optionally substituted aryl group or heterocyclic group, (3) optionally substituted aryl lower alkylcarbamoyl group, (4) amino acid or ester thereof A carbonyl group substituted with a group in which one hydrogen atom has been removed from the amino group or (5) an optionally esterified carboxyl group,
Y is an alkylene group which may have a cycloalkylene group at the terminal, an alkenylene group, an alkynylene group or a tricycloalkylene group, R ³ and R ⁴ are different, one is a hydrogen atom, the other is a lower alkoxy group, or a substituent Or, an unsubstituted phenoxy group, R ⁵ and R ⁶ are different from each other, a hydrogen atom or a hydroxy group, R ⁷ , R ⁸ and R ⁹ are hydrogen atoms or a hydroxy group, R ⁷ is a hydroxy group, R ⁸ and R ⁹ are different from each other. Is a group, or R ⁷ and R ⁸ are bonded to each other at the terminals to form a lower alkylenedioxy group, and R ⁹ is a hydrogen atom. ).

The object [I] of the present invention is N- at the 6-position of the sugar.
It has a structural feature of introducing an acyl-N-alkylamino group, an N-acyl-N-alkenylamino group, or the like, and is superior to or equivalent to the 1-position substitution product in infection protection and / or leukocyte increasing activity. Therefore, it is a pharmaceutical compound useful as an infection protective agent or an anti-infection enhancing agent.

Examples of the aryl group in the present invention include:
Examples thereof include a phenyl group, a naphthyl group, and a tetrahydronaphthyl group, and examples of the heterocyclic group include a monocyclic or bicyclic group containing 1 to 2 heteroatoms selected from nitrogen atom, oxygen atom and sulfur atom. Examples of the heterocyclic group include benzofuranyl group, pyridyl group, thienyl group, imidazolyl group, thiazolyl group, oxazolyl group, and the like.
Examples thereof include a pyrazolyl group, a pyrrolyl group, a pyrazinyl group, an indolyl group, a quinolyl group and a benzothienyl group. Examples of the substituents on the aryl group, heterocyclic group and phenoxy group include a lower alkyl group, a lower alkoxy group, a lower alkanoyl group, an optionally esterified carboxyl group, a halogen atom, a phenyl group and a lower alkanoyl group. Alternatively, an amino group which may be substituted with a phenyl lower alkoxycarbonyl group, a nitro group, a mono- or di-lower alkylcarbamoyl group, a piperidinocarbonyl group and the like can be mentioned. In addition, examples of amino acids include natural protein amino acids and their enantiomers or racemates, and alanine, leucine, phenylalanine, valine, isoleucine and the like are preferable.

Further, examples of the ester in the esterified carboxyl group or amino acid ester include lower alkyl ester, phenyl lower alkyl ester and the like. Of these, methyl ester, ethyl ester and benzyl ester are preferable.

An example of the alkylene group having a cycloalkylene group at the terminal is an alkylene group having a cyclohexylene group at the terminal, and an example of a tricycloalkylene group is a group forming an adamantyl group with adjacent R ^2. Can be given.

Specific examples of the object [I] of the present invention include:
R ¹ is (1) hydrogen atom, (2) lower alkyl group, lower alkoxy group, lower alkanoyl group, optionally esterified carboxyl group, halogen atom, phenyl group,
It may be substituted with 1 to 3 groups selected from an amino group, which may be substituted with a lower alkanoyl group or a phenyl lower alkoxycarbonyl group, a nitro group, a mono- or di-lower alkylcarbamoyl group and a piperidinocarbonyl group. Good phenyl group, (3) naphthyl group,
(4) Tetrahydronaphthyl group, (5) Benzofuranyl group, (6) Pyridyl group or (7) Thienyl group, X is a single bond, linear alkylene group or linear alkenylene group, R ²
Of (1) hydrogen atom, (2) phenyl group, (3) phenyl lower alkylcarbamoyl group optionally substituted by 1 to 3 lower alkoxy groups, (4) alanine, leucine or phenylalanine or an ester thereof. A carbonyl group substituted with a group obtained by removing one hydrogen atom from an amino group or (5) an optionally esterified carboxyl group, Y is a linear alkylene group, a linear alkylene group having a cyclohexylene group at the terminal, A straight chain alkenylene group or a straight chain alkynylene group, or a group forming an adamantyl group with adjacent R ² , R ³ and R ⁴ are different,
One is a hydrogen atom, the other is a lower alkoxy group or a phenoxy group, R ⁵ and R ⁶ are different, and a hydrogen atom or a hydroxy group, R ⁷ , R ⁸ and R ⁹ are as follows: R ⁷ is a hydroxy group, R
⁸ and R ⁹ are different and are a hydrogen atom or a hydroxy group, or R ⁷ and R ⁸ are bonded to each other at a terminal to form a lower alkylenedioxy group, and R ⁹ is a hydrogen atom. To be

Among these, preferred compounds in terms of their medicinal effects are: R ¹ is (1) hydrogen atom, (2) lower alkoxy group,
A phenyl group which may be substituted with 1 to 2 groups selected from an optionally esterified carboxyl group, a halogen atom and a piperidinocarbonyl group, or (3) a naphthyl group, and X is a single bond, Linear alkylene group or linear alkenylene group, R ² is hydrogen atom or phenyl group, Y is linear alkylene group or alkenylene group, R ³ and R ⁴ are different, one is hydrogen atom, the other is lower alkoxy group, R
Examples are compounds in which ⁵ is a hydrogen atom, R ⁶ and R ⁷ are hydroxy groups, and R ⁸ and R ⁹ are different and are hydrogen atoms or a hydroxy group.

From the viewpoint of efficacy, more preferable compounds are R
¹ is a hydrogen atom or a phenyl group, X is a linear alkylene group,
R ² is a hydrogen atom, Y is a linear alkylene group or a linear alkenylene group, R ³ , R ⁵ and R ⁸ are hydrogen atoms, R ⁴ is a lower alkoxy group, and R ⁶ , R ⁷ and R ⁹ are hydroxy groups. Compounds.

The object [I] of the present invention includes both an optically active substance and a mixture thereof.

The object [I] of the present invention can be used in medicinal use either in the free form or in the form of its pharmacologically acceptable salt. Examples of such salts include alkali metal salts, alkaline earth metal salts, amino acid salts, organic acid salts (succinic acid, maleic acid, tartaric acid, methanesulfonic acid, etc.), mineral acid salts and the like.

The object [I] of the present invention can be used either for oral administration or parenteral administration, and can be used as a pharmaceutical preparation by mixing with an excipient suitable for oral or parenteral administration. Further, the pharmaceutical preparation may be a solid preparation such as a tablet, a capsule or a powder, or a liquid preparation such as a solution, a suspension or an emulsion. Further, for parenteral administration, it can be used in the form of injection.

The dose varies depending on the age, weight, condition of the patient or the degree of disease, but the daily dose is usually 1 to 500 mg / kg, especially 10 to 100 mg / kg in the case of oral administration. For parenteral administration,
0.1-500 mg / kg, especially 1-100 mg /
It is preferably kg.

According to the present invention, the target [I] is, for example, a compound of the general formula [II]

[0021]

[Chemical 6]

[Wherein the symbols have the same meanings as defined above] and the amino sugar compound or salt thereof and the general formula [III]

[0023]

[Chemical 7]

It can be produced by reacting with a carboxylic acid compound represented by the formula (wherein the symbols have the same meaning as described above), a salt thereof or a reactive derivative thereof.

The condensation reaction of the amino sugar compound [II] or its salt with the carboxylic acid compound [III] or its salt can be carried out in a suitable solvent in the presence of a dehydrating agent.
Examples of the dehydrating agent include dicyclohexylcarbodiimide and carbonyldiimidazole. As the salt of the amino sugar compound [II], a commonly used salt such as a mineral acid salt such as hydrochloride or an organic acid salt such as fumarate, maleate, malate and oxalate can be used. On the other hand, as the salt of the carboxylic acid compound [III], a conventional salt such as an alkali metal salt or an alkaline earth metal salt can be used, and these salts are preliminarily released in the reaction with the amino sugar compound [II]. It is preferable to use it as a carboxylic acid for the reaction.

The condensation reaction between the amino sugar compound [II] or a salt thereof and the reactive derivative of the carboxylic acid compound [III] may be carried out in a suitable solvent in the presence or absence of a deoxidizing agent. it can. As the reactive derivative, for example, any of those commonly used for acid amide condensation such as acid halide, mixed acid anhydride and active ester can be used. Examples of the deoxidizing agent include alkali metal hydroxide, alkali metal carbonate, alkali metal hydrogen carbonate, tri-lower alkylamine, N, N-di-lower alkylaniline, pyridine and the like.

The reaction solvent may be an inert solvent which does not adversely affect the reaction in any condensation reaction, and preferred examples thereof include trichloromethane, dichloromethane, dioxane and tetrahydrofuran. In addition, these condensation reactions can be suitably carried out from under cooling at the boiling point of the solvent, for example, -20 ° C to 70 ° C, especially 0 ° C to 20 ° C.

The object [I] of the present invention obtained above is
Mutual conversion is possible if necessary. For example,
The compound [I] in which R ¹ is an amino group-substituted phenyl group is
A compound [I] which is a phenyl lower alkoxycarbonylamino group-substituted phenyl group can also be produced by catalytic reduction, and a compound [I] in which R ¹ is a lower alkanoylamino group-substituted phenyl group is a compound [I] in which R ¹ is an amino group. It can also be produced by subjecting a compound which is a substituted phenyl group and a lower alkanoyl halide to a condensation reaction.

A compound in which R ² is a carbonyl group substituted with a group obtained by removing one hydrogen atom from the amino group of an amino acid or its ester, or an optionally substituted lower arylalkylcarbamoyl group [I ] Is R ²
It can also be produced by reacting a compound [I] in which is a carboxyl group with the corresponding amine compound.

Any of the above interconversion reactions can be carried out according to a conventional method. The catalytic reduction can be carried out, for example, at room temperature, atmospheric pressure and in the presence of palladium-carbon, and the condensation reaction with the lower alkanoyl halide can be carried out by using a deoxidizing agent (alkali metal hydroxide, alkali metal carbonate, alkali metal hydrogen carbonate, tricarbonate). Lower alkylamine, N, N-di-lower alkylaniline, pyridine, etc.). The condensation reaction with the corresponding amine compound can be carried out in the presence of a dehydrating agent (dicyclohexylcarbodiimide, carbonyldiimidazole, etc.).

The starting compound [II] of the present invention is, for example,
General formula [IV]

[0032]

[Chemical 8]

(Wherein the symbols have the same meanings as described above) and the compound of the general formula [V]

[0034]

[Chemical 9]

(Wherein the symbols have the same meanings as described above) and an amine compound according to a conventional method, for example, in the presence or absence of a reaction accelerator (eg sodium iodide), It can be manufactured by reacting with heating (for example, 50 to 180 ° C.) in a solvent or without a solvent.

In the present specification, examples of the alkylene group include alkylene groups having 1 to 21 carbon atoms,
The alkenylene group and the alkynylene group have 2 carbon atoms.
To 17 are alkenylene groups and alkynylene groups, and examples of the cycloalkylene group include cycloalkylene groups having 4 to 7 carbon atoms. Also, a lower alkyl group,
The lower alkylene group and the lower alkoxy group include those having 1 to 6 carbon atoms, and the lower alkanoyl group includes those having 2 to 6 carbon atoms. Further, the alkylene group, alkenylene group, alkynylene group, alkyl group and alkoxy group include linear and branched ones.

[0037]

【Example】

Example 1 To a solution of 1.16 g of methyl 6-deoxy-6- (4-phenylbutyl) amino-α-D-glucopyranoside in 20 ml of tetrahydrofuran was added 0.73 g of triethylamine, and while stirring, 1.3 g of octadecanoyl chloride.
Add. After stirring overnight at room temperature, the precipitate was filtered off, the filtrate was concentrated under reduced pressure, and the resulting residue was subjected to silica gel column chromatography (solvent; chloroform: methanol = 1).
5: 1) and methyl 6-deoxy-6- [N-
1.56 g of octadecanoyl-N- (4-phenylbutyl) amino] -α-D-glucopyranoside is obtained as a caramel.

Yield: 73% MASS (m / z): 592 IR ^neat ν _max (cm ⁻¹ ): 3350, 1640 Example 2-13 Corresponding raw material compound and corresponding carboxylic acid compound obtained in Reference Example 1-4 Are treated in the same manner as in Example 1 to obtain the compounds shown in Tables 1 and 2 below.

[0039]

[Table 1]

[0040]

[Table 2]

Example 14 Methyl 6-deoxy-6- [4- (4-methoxyphenyl) butyl] amino-α-D-glucopyranoside 1.1
To a 25 ml solution of 5 g of tetrahydrofuran, 740 mg of potassium carbonate and 8 ml of water are added, and a tetrahydrofuran solution of 1.08 g of octadecanoyl chloride is added dropwise with stirring under ice cooling, followed by stirring for 15 minutes. Further, 1 ml of methanol was added, the mixture was stirred for 30 minutes, extracted with ethyl acetate, the extract was washed and dried, the solvent was distilled off, and the obtained residue was subjected to silica gel column chromatography (solvent; chloroform: methanol = 20: 1) and methyl 6-deoxy-6- {N-octadecanoyl-N- [4- (4
1.91 g of -methoxyphenyl) butyl] amino} -α-D-glucopyranoside is obtained as an oil.

Yield: 95% MASS (m / z): 622 IR ^neat ν _max (cm ⁻¹ ): 3400, 1620 Examples 15-63 Corresponding raw material compounds and corresponding carvone obtained in Reference Examples 1 and 3-38. The acid compound is treated in the same manner as in Example 14 to obtain the compounds shown in Tables 3 to 9 below.

[0043]

[Table 3]

[0044]

[Table 4]

[0045]

[Table 5]

[0046]

[Table 6]

[0047]

[Table 7]

[0048]

[Table 8]

[0049]

[Table 9]

Example 64 Methyl 6-deoxy-6- [N- (5-methoxycarbonylpentanoyl) -N-undecylamino] -α-D
-A solution of 0.5 g of glucopyranoside in 20 ml of methanol was added dropwise with 2 ml of 10% sodium hydroxide solution under ice cooling, and the mixture was stirred overnight at room temperature. The reaction solution was concentrated under reduced pressure, and the concentrated solution was subjected to column chromatography packed with SP-207 [high-porous polymer (Mitsubishi Chemical Industries)] (solvent; methanol: water = 20: 70, 50:50, 70:30).
And methyl 6-deoxy-6- [N- (5-carboxypentanoyl) -N-undecylamino] -α.
0.25 g of -D-glucopyranoside sodium salt is obtained as a powder.

MASS (m / z): 520 IR ^nujol ν _max (cm ^-1 ): 3300,1640 Example 65 Methyl 6-deoxy-6- [N- (5-methoxycarbonylpentanoyl) -N- (4 -Phenylbutyl) amino] -α-D-glucopyranoside was treated as in Example 64 to give methyl 6-deoxy-6- [N- (5-carboxypentanoyl) -N- (4-phenylbutyl) amino. ] -Α-D-Glucopyranoside sodium salt is obtained as a powder.

^Yield : 56% MASS (m / z): 498 IR ^nujol ν _max (cm ^-1 ): 3300,1640 Example 66 (1) Methyl 6-deoxy-6- [N- (5-methoxycarbonyl) To a solution of 0.5 g of pentanoyl) -N- (4-phenylbutyl) amino] -α-D-glucopyranoside in 10 ml of methanol was added an aqueous solution of 1.5 ml of 10% sodium hydroxide under ice cooling, and the mixture was stirred at room temperature overnight. After distilling off methanol under reduced pressure, the residue was adjusted to pH 3 with 10% hydrochloric acid.
And extract with 30 ml of chloroform. The extract was washed and dried, the solvent was distilled off, and methyl 6-deoxy-6-
0.38 g of [N- (5-carboxypentanoyl) -N- (4-phenylbutyl) amino] -α-D-glucopyranoside is obtained as an oil.

Yield: 78% MASS (m / z): 454 IR ^neat ν _max (cm ⁻¹ ): 3300,1710,1610 (2) 0.38 g of dicyclohexylcarbodiimide in a solution of 0.68 g of this product in tetrahydrofuran. 1
-Adding 0.22 g of hydroxybenzotriazole,
After stirring at -10 ° C for 10 minutes, 0.31 g of L-alanine methyl ester hydrochloride and 0.23 g of triethylamine are added, and the mixture is stirred at room temperature for 20 hours, and then the precipitate is filtered off.
The filtrate was concentrated under reduced pressure, and the resulting residue was subjected to silica gel column chromatography (solvent; chloroform: methanol =
10: 1) to give methyl 6-deoxy-6- {N
0.5 g of-[((S) -1-methoxycarbonylethyl) aminocarbonyl] pentanoyl-N- (4-phenylbutyl) amino} -α-D-glucopyranoside is obtained as a caramel.

Yield: 62% MASS (m / z): 539 IR ^neat ν _max (cm ⁻¹ ): 3300,1750,1620 Example 67-71 Methyl 6-deoxy-6- [N- (5-carboxy Pentanoyl) -N- (4-phenylbutyl) amino] -α
-D-Glucopyranoside and the corresponding amine compound are treated in the same manner as in Example 66- (2) to give compounds shown in Table 10 below.

[0055]

[Table 10]

Example 72 Methyl 6-deoxy-6- (4-phenylbutyl) amino-3,4-isopropylidene-β-D-galactopyranose and octadecanoyl chloride were treated as in Example 14. , Methyl 6-deoxy-6- [N-octadecanoyl-N- (4-phenylbutyl) amino]-
3,4-isopropylidene-β-D-galactopyranose is obtained as an oil.

MASS (m / z): 632 IR ^neat ν _max (cm ^-1 ): 3400,1640 Example 73 Methyl 6-deoxy-6- (4-phenylbutyl) amino-β-D-galactopyranose and octa Treatment with decanoyl chloride in the same manner as in Example 14 to give methyl 6-deoxy-6- [N-octadecanoyl-N- (4-phenylbutyl) amino] -β-D-galactopyranose as an oil. obtain.

Yield: 86% MASS (m / z): 592 IR ^neat ν _max (cm ^-1 ): 3400,1640 Example 74 Methyl 6-deoxy-6- {N-octadecanoyl-N
-[4- (4-benzyloxycarbonylphenyl)-
900 mg of 10% palladium-carbon is added to a solution of 1.96 g of 3-butenyl] amino} -α-D-glucopyranoside in 15 ml of tetrahydrofuran and 5 ml of ethanol, and catalytic reduction is performed at room temperature and atmospheric pressure. After 3 hours, the catalyst is filtered off and the filtrate is concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (solvent; chloroform: methanol = 9: 1), methyl 6-deoxy-6.
-{N-octadecanoyl-N- [4- (4-carboxyphenyl) butyl] amino} -α-D-glucopyranoside is obtained as an oil. Yield: 82% MASS (m / z): 636 IR ^neat ν _max (cm ⁻¹ ): 3380,1715,1610 Example 75 (1) Methyl 6-deoxy-6- {N-octadecanoyl-N- [4- (4-Benzyloxycarbonylaminophenyl) butyl] amino} -α-D-glucopyranoside was treated as in Example 74 to give methyl 6-deoxy-6- {N-octadecanoyl-N- [. 4- (4-aminophenyl) butyl] amino} -α-D-glucopyranoside is obtained as an oil.

Yield: 97% MASS (m / z): 607 IR ^neat ν _max (cm ^-1 ): 3360,1630 (2) To a solution of 400 mg of this product in 20 ml of tetrahydrofuran was added 150 mg of potassium carbonate and 4 ml of water, and ice was added. A solution of hexanoyl chloride (100 mg) in tetrahydrofuran (3 ml) is added dropwise with stirring under cooling. One hour later,
After adding 2 ml of methanol and stirring for 1 hour, the solvent is distilled off and the mixture is extracted with ethyl acetate. The extract was washed and dried, the solvent was evaporated, and the obtained residue was subjected to silica gel column chromatography (solvent; chloroform: methanol = 10:
1) and methyl 6-deoxy-6- {N-octadecanoyl-N- [4- (4-n-hexanoylaminophenyl) butyl] amino} -α-D-glucopyranoside as an oil. obtain.

Yield: 98% MASS (m / z): 705 IR ^neat ν _max (cm ^-1 ): 3400,1660,1620 Example 76-78 Methyl 6-deoxy-6- (4-phenylbutyl) amino The -α-D-glucopyranoside and the corresponding carboxylic acid compound are treated in the same manner as in Example 14 to obtain the compounds shown in Table 11 below.

[0061]

[Table 11]

Reference Example 1 To a solution of 15 g of methyl 6-tosyl-α-D-glucopyranoside in 70 ml of dimethylformamide was added 19.3 g of 4-phenylbutylamine, and the mixture was reacted at 90 ° C. for 7 hours. After the reaction, the mixture was concentrated under reduced pressure, and the obtained residue was purified by silica gel column chromatography (solvent; chloroform: methanol = 15: 1 to 10: 1) to give methyl 6-deoxy-6- (4-phenylbutyl) amino. 9.71 g of -α-D-glucopyranoside is obtained as a caramel.

Yield: 69% MASS (m / z): 326 IR ^neat ν _max (cm ⁻¹ ): 3350 Reference Example 2-4 The corresponding raw material compound was treated in the same manner as in Reference Example 1, and the following first
The compounds listed in Table 2 are obtained.

[0064]

[Table 12]

Reference Example 5 Methyl 6-tosyl-α-D-glucopyranoside 1.5 g
2.7 g of 4- (4-methoxyphenyl) butylamine is added to a solution of 30 ml of toluene in, and the mixture is heated under reflux for 15 hours. The reaction solution was concentrated under reduced pressure, and the resulting residue was purified by silica gel column chromatography (solvent; chloroform: methanol: ammonia water = 20: 5: 1) to give methyl 6-deoxy-6- [4- (4 -Methoxyphenyl)
Butyl] amino-α-D-glucopyranoside 1.21 g
As an oil.

Yield: 79% MASS (m / z): 356 IR ^neat ν _max (cm ⁻¹ ): 3400 Reference Example 6-38 The corresponding starting compound was treated in the same manner as in Reference Example 5 to give the following 1st
The compounds listed in Tables 3 to 17 are obtained.

[0067]

[Table 13]

[0068]

[Table 14]

[0069]

[Table 15]

[0070]

[Table 16]

[0071]

[Table 17]

Reference Example 39 Methyl 6-tosyl-3,4-isopropylidene-β-D
-Glucopyranoside was treated as in Reference Example 5 to give methyl 6-deoxy-6- (4-phenylbutyl) amino-
3,4-isopropylidene-β-D-gelcopyranoside is obtained as an oil.

Yield: 95% MASS (m / z): 366 IR ^neat ν _max (cm ⁻¹ ): 3180 Reference Example 40 Methyl 6-deoxy-6- (4-phenylbutyl) amino-3,4-isopropyi 11 ml of 10% hydrochloric acid was added to a solution of 3.0 g of lidene-β-D-galactopyranose in 50 ml of methanol, and the mixture was stirred at room temperature for 4 hours, adjusted to pH 8 with 10% aqueous sodium hydroxide solution, and concentrated under reduced pressure. The obtained residue is subjected to silica gel column chromatography (solvent; chloroform: methanol: ammonia water = 10:
2: 0.2) and methyl 6-deoxy-6- (4
1.9 g of -phenylbutyl) amino-β-D-galactopyranose are obtained as an oil.

Yield: 71% MASS (m / z): 326 IR ^neat ν _max (cm ^-1 ): 3350

[0075]

The acylamino sugar derivative [I], which is the object of the present invention, has the structural characteristics of introducing an acylamino group at the 6-position of the sugar, and is equivalent to the 1-position substitution product which is a known compound. Since it exhibits the above-mentioned excellent infection-protecting action, it is a useful pharmaceutical compound as an infection-protecting agent or an anti-infection enhancing agent.

Specifically, it exhibits a protective effect against bacterial and fungal infections and / or an antitumor effect, is useful for general prevention against infectious diseases in humans and animals, and also has an innate or acquired immunity. It can be suitably used for deficiency, particularly acquired immunodeficiency due to a severe primary modulation state after radiotherapy or treatment with a substance having immunosuppressive activity. The compounds of the present invention also have a leukocytosis effect. In addition, the compounds of the present invention may also be administered in combination with anti-infective and anti-cancer antibiotics or other chemotherapeutic agents or other drug treatments, preferably to offset immunodeficiency.

Claims (10)

[Claims] 1. A compound represented by the general formula [I]: (However, R ¹ is a hydrogen atom, or an aryl group or a heterocyclic group which may have a substituent, X is a single bond, an alkylene group, an alkenylene group or an alkynylene group, and R ² is a (1) hydrogen atom. From (2) an optionally substituted aryl group or heterocyclic group, (3) optionally substituted aryl lower alkylcarbamoyl group, (4) an amino group of an amino acid or its ester Hydrogen atom 1
A carbonyl group substituted with groups other than the above or (5) an optionally esterified carboxyl group, Y is an alkylene group which may have a cycloalkylene group at the end, an alkenylene group, an alkynylene group or tricyclo Alkylene groups, R ³ and R ⁴ are different, one is a hydrogen atom, the other is a lower alkoxy group, or a substituted or unsubstituted phenoxy group, R ⁵ and R ⁶ are different, a hydrogen atom or a hydroxy group, R ⁷ , R ⁸ and R ⁹ , R ⁷ is a hydroxy group, R
⁸ and R ⁹ are different and are a hydrogen atom or a hydroxy group, or R ⁷ and R ⁸ are bonded to each other at a terminal to form a lower alkylenedioxy group, and R ⁹ is a hydrogen atom. . ] The acylamino sugar derivative shown by these, or its pharmacologically acceptable salt. 2. R ¹ is (1) hydrogen atom, (2) lower alkyl group, lower alkoxy group, lower alkanoyl group, optionally esterified carboxyl group, halogen atom, phenyl group, lower alkanoyl group or phenyl. 1 to 1 selected from an amino group optionally substituted with a lower alkoxycarbonyl group, a nitro group, a mono- or di-lower alkylcarbamoyl group and a piperidinocarbonyl group
Phenyl group optionally substituted with 3 groups, (3) naphthyl group, (4) tetrahydronaphthyl group, (5) benzofuranyl group, (6) pyridyl group, (7) thienyl group,
(8) Imidazolyl group, (9) Thiazolyl group, (10)
Oxazolyl group, (11) pyrazolyl group, (12) pyrrolyl group, (13) pyrazinyl group, (14) indolyl group, (15) quinolyl group or (16) benzothienyl group, X is a single bond, straight chain alkylene group Or a straight chain alkenylene group, R ² is (1) a hydrogen atom, (2) a phenyl group,
(3) Substituted with a phenyl lower alkylcarbamoyl group which may be substituted with 1 to 3 lower alkoxy groups, (4) alanine, leucine, or a group obtained by removing one hydrogen atom from the amino group of phenylalanine or their esters. The compound according to claim 1, which is a carbonyl group or (5) an optionally esterified carboxyl group. 3. R ¹ is substituted with 1 to 2 groups selected from (1) hydrogen atom, (2) lower alkoxy group, optionally esterified carboxyl group, halogen atom and piperidinocarbonyl group. A phenyl group, which may be
Or (3) naphthyl group, X is a single bond, linear alkylene group or linear alkenylene group, R ² is hydrogen atom or phenyl group, Y is linear alkylene group or linear alkenylene group,
R ³ and R ⁴ are different, one is a hydrogen atom, the other is a lower alkoxy group, R ⁵ is a hydrogen atom, R ⁶ and R ⁷ are hydroxy groups, R ⁸ and R ⁹ are different, and a hydrogen atom or a hydroxy group. A compound according to claim 2. 4. R ¹ is a hydrogen atom or a phenyl group, X is a linear alkylene group, R ² is a hydrogen atom, Y is a linear alkylene group or a linear alkenylene group, and R ³ , R ⁵ and R ⁸ are hydrogen atoms. , R ⁴ is a lower alkoxy group, and R ⁶ , R ⁷ and R ⁹ are hydroxy groups. 5. R ¹ is a phenyl group, X is a tetramethylene group, R ² is a hydrogen atom, Y is a heptadecamethylene group,
R ³ , R ⁵ and R ⁸ are hydrogen atoms, R ⁴ is a methoxy group, R
The compound according to claim 4, wherein ⁶ , R ⁷ and R ⁹ are hydroxy groups. 6. R ¹ is a phenyl group, X is a tetramethylene group, R ² is a hydrogen atom, Y is a heptamethylene group, R ³ and R.
⁵ and R ⁸ are hydrogen atoms, R ⁴ is a methoxy group, R ⁶ and R ⁷
The compound according to claim 4, wherein R ⁹ and R ⁹ are hydroxy groups. 7. R ¹ is a hydrogen atom, X is a heptamethylene group, R ² is a hydrogen atom, Y is a heptadecamethylene group,
R ³ , R ⁵ and R ⁸ are hydrogen atoms, R ⁴ is a methoxy group, R
The compound according to claim 4, wherein ⁶ , R ⁷ and R ⁹ are hydroxy groups. 8. R ¹ is a hydrogen atom, X is an octadecamethylene group, R ² is a hydrogen atom, Y is an undecamethylene group,
R ³ , R ⁵ and R ⁸ are hydrogen atoms, R ⁴ is a methoxy group, R
The compound according to claim 4, wherein ⁶ , R ⁷ and R ⁹ are hydroxy groups. 9. R ¹ is a phenyl group, X is a tetramethylene group, —Y—R ² is a 9-decenyl group, R ³ , R ⁵ and R ⁸
Is a hydrogen atom, R ⁴ is a methoxy group, and R ⁶ , R ⁷ and R ⁹ are hydroxy groups. 10. A compound represented by the general formula [II]: (In the formula, R ¹ is a hydrogen atom, or an aryl group or a heterocyclic group which may have a substituent, X is a single bond, an alkylene group, an alkenylene group or an alkynylene group, and R ³ and R ⁴ are different. One of them is a hydrogen atom, the other is a lower alkoxy group, or a substituted or unsubstituted phenoxy group, R ⁵ and R ⁶ are different from each other, and a hydrogen atom or a hydroxy group, R ⁷ ,
Or R ⁸ and R ^9, R ⁷ is hydroxy group, and R ⁸ and R ⁹ are different, a hydrogen atom or a hydroxy group, or,
R ⁷ and R ⁸ are bonded to each other at the terminals to form a lower alkylenedioxy group, and R ⁹ is a hydrogen atom. ) An amino sugar compound represented by the formula) or a salt thereof and a compound represented by the general formula [III]: (In the formula, R ² is (1) hydrogen atom, (2) optionally substituted aryl group or heterocyclic group, (3) optionally substituted aryl lower alkylcarbamoyl A group, (4) a carbonyl group substituted with a group obtained by removing one hydrogen atom from an amino group of an amino acid or its ester, or (5) a carboxyl group which may be esterified, and Y has a cycloalkylene group at the terminal. An alkylene group, an alkenylene group, an alkynylene group, or a tricycloalkylene group which may be added), a salt thereof or a reactive derivative thereof. ] [Chemical 4] (In the formula, symbols have the same meanings as described above.) A process for producing an acylamino sugar derivative or a pharmaceutically acceptable salt thereof.