JPS58116489A - Carboxylic acid amide derivative - Google Patents

Abstract

NEW MATERIAL:An carboxylic acid amide derivative shown by the formulaI (R<1> is H, or halogen; R<2> and R<3> are H, lower alkyl, cycloalkyl, phenyl lower alkyl, lower alkenyl, etc.; X is lower alkylene which may have phenyl group). EXAMPLE:N-Methyl-alpha-(thiazolo[5,4-b]pyridine-2-yl)thiophenylacetic amide. USE:An antiphlogistic. A hypotensor, anodyne, and antipyretic. PROCESS:A 2-mercaptothiazolo[5,4-b]pyridine derivative shown by the formula II is reacted with a haloamide derivative shown by the formula III(Y is halogen such as F, Cl, Br, orI) in the presence of a deoxidizer (e.g., pyridine, triethylamine, etc., preferably NaOH, etc.), to give a compound shown by the formulaI. The reaction is carried out in a proper solvent (e.g., benzene, toluene, etc.).

Description

[Detailed description of the invention] The present invention relates to novel carboxylic acid amide derivatives.

The carboxylic acid amide derivative of the present invention is a novel compound that has not been described in any literature, and is represented by the following general formula [I].

[In the formula, R1 represents a hydrogen atom or a halogen atom.

R2 and R3 are the same or different and are a hydrogen atom, a lower alkyl group, a phenyl lower alkyl group, a lower alkenyl group, a nido group, a halogen atom, a lower alkyl group, a lower alkoxy group Refers to a phenyl group having 91 to 3 substituents selected from the group consisting of a dicarbonyl group, a lower alkyl group, and a hexogen-substituted lower alkyl group. X represents a lower alkyl group which may have a phenyl group as a substituent. ] The compound of the present invention represented by the general formula CI) has excellent anti-inflammatory, hypotensive, analgesic, and antipyretic effects, and is useful as an anti-inflammatory agent, antihypertensive agent, analgesic agent, and antipyretic agent.

Specifically, each group shown in the above general formula (:I) can be exemplified by the following groups.

Examples of the halogen atom include fluorine atom, chlorine atom, bromine atom, and iodine atom.

Examples of the lower alkyl group include methyl, ethyl, dimethyl, isopropyl, butyl, pentyl, and hesyl groups.

Examples of the Schifol group include Schifopyl, cyclobutyl, Schiffpentyl, Schiffoxyl, SchiffO
Examples include heptyl, Schiffoctyl, and the like.

Zyl, α-phenethyl, β-phenethyl, 3-phenylpropyl, 4-phenylbutyl, 1,1-dimethyl-2
-phenylethyl, 5-phenylethyl, 6-phenyl, and the like.

Examples of the lower alkenyl group include 2-benyl, 2-benyl,
-butenyl, 3-butenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl and 4-hedecenyl radicals may be mentioned.

Examples of the lower alkoxy groups include meth-10, etho-10, prop-2, iso-1, iso-1, and tart-.
Examples include butoshi group.

Examples of the lower alkoxycarbonyl group include methocodicarbonyl, ethocyclodicarbonyl, dicarbonyl, isozodicarbonyl, carbonyl, and tart-butocodicarbonyl. can be mentioned.

Examples include fluoromethyl, trichloromethyl, and 2,2.2-trifluoroethyl groups.

Nido O group, halogen atom, lower alkoxy group, Ta1-3
Examples of the phenyl group which may have 4 substituents include phenyl, 4-methylphenyl, 3-trifluoromethylphenyl, 3,4-di,ethylphenyl, 3,4
．． 5-) Limethylphenyl, 2-ethylphenyl, 4
-tricOOmethylphenyl, 2-methoxydiphenyl,
3.4-dimeth+diphenyl, 3,4,5-)rimeth+diphenyl, 3-ethodiphenyl1.4-methodiphenyl, 0 lophenyl, 2=4-, l;
0 phenyl, 2,6-dichlorophenyl, 3,4.5-
) RikuOO phenyl, 3,4-diz(]E”7enyl, 4-?dio0 phenyl, 2-fluorophenyl, 2-
200 phenyl, 3-4-;
phenyl, 4-nido phenyl, 2-nido phenyl,
Examples include 2-methoxycarboxylic acid, luponylphenyl, and 4-ethoxycarbonylphenyl groups.

Examples of lower alkali groups which may have a phenyl group as a substituent include methylenedi, ethylene, pyrene, isozylene, pyrene, pentamethylene, hesylmethylene, methylmethylene, phenylmethylene, 1
-Phenylethylene, 2-phenylethylene, l-phenylpropylene, 2-phenylpropylene, 3-phenylpyrene, l-phenylethylene, 2-phenylethylene, 3-phenylbutylene, 4-phenylbutylene, ■ -Phenylpentamethylene, 2-phenylpentamethylene, 3-phenylpentamethylene, 4-phenylpentamethylene, 5-phenylpentamethylene, 1-phenylbentamethylene, 2-phenylbentamethylene, 3
Examples include -phenyl methylene, 4-phenyl methylene, 5-phenyl methylene, 6-phenyl methylene, and the like.

The compound of the present invention can be produced by various methods, but one preferred example is as shown in the reaction formula below:
By reacting the 2-merca-dithiazilo[5,4-h)pyridine derivative represented by the general formula [II] with the haO3do derivative represented by the general formula (I) in the presence of an acid absorbing agent. Manufactured.

Reaction formula % Formula % [In the formula, Y represents fluorine, chlorine, bromine, iodine atoms, etc. ] As the deoxidizing agent used in the reaction between the compound of the general formula [■] and the compound of the general formula, a wide variety of conventionally known basic compounds can be used. Examples include inorganic bases such as N-methylmorpholoxy, triethylene, sodium methoxy, potassium methoxy, sodium ethyl ester, and potassium ethyl ester. Among these, it is advantageous to use deoxidizers as inorganic bases. The above reactions are generally carried out in a suitable solvent.

As a solvent, any known book can be used as long as it does not adversely affect the reaction. Specifically, Pent! Aromatic or aliphatic hydrocarbons such as toluene, toluene, petroleum ether, chain or cyclic ethers such as ethyl ether, methylphenylene ether, tetrahydrofurazine, dioxane, acetone, methyl ethyl ketone, acetophenone, etc. Ketones, methanol, ethanol, lower alcohols such as isodol-panol, and the like are appropriately selected and used depending on the type of deoxidizing agent used, the properties of the raw materials, and other reaction conditions. In this reaction, when using as a starting material a compound in which Y represents a halogen atom other than an iodine atom among the compounds of the general formula, potassium iodide,
Preferably, an alkali metal iodide compound such as sodium iodide is present.

In the above reaction, the ratio of the compound of general formula (III) and the compound of general formula (III) to be used is not particularly limited and can be appropriately selected from a wide range, but usually the latter is used in equimolar excess to the former, preferably It is preferable to use an equivalency culm.The reaction may be carried out under cooling, at room temperature, or under heating, but it is usually preferable to carry out between room temperature and the reflux temperature of the solvent.The reaction is generally carried out at 3. It will take about 12 hours.

The compounds of the invention thus obtained can be separated by conventional separation means,
For example, solvent extraction, recrystallization, column extraction,
It can be easily isolated and purified using a thin layer of magnetic tape. Next, the present invention will be explained in more detail with reference to Examples.

Example I N-methyl-a-200 phenyl acetic acid eamide 1.8 f
was dissolved in 30 μl of acetone, then 1 μl of sodium iodide
．． Add 5 f and heat to reflux for 3 hours. After cooling, add 2-merkazutothiadi[1[5,4-b]pyridine 1 while stirring.
．． 6 and anhydrous sodium carbonate 1. Add Of and 6 again
Heat to reflux for an hour. After cooling, 100% of water was added to the reaction mixture.
and extracted with RI00 form. Dry over porcelain, treat
The solvent is distilled off.

The residue was eluted with gel strength 5 muk 0 methanol (20:1) with form/methanol (20:1) > IIC, and N
-Methyl-α-(thiarylo[5,4-b)pyridine-
2-yl)thiophenyl acetate amide was obtained. Benzene-
The mixture was recrystallized into roux and sashimi to obtain 1.3 tons of light brown needle crystals. mp 155.5-157.0°C (decomposition) Examples 2 to 14 Each compound listed in Table 1 below is obtained in the same manner as in Example 1 above.

Claims (1)

[Claims] ■ General formula [wherein R1 represents a hydrogen atom or a halogen atom]. R2 and R3 are the same or different and are a hydrogen atom, a lower alkyl group, a phenyl lower alkyl group, a lower alkenyl group, a nido group, a halogen atom, a lower alkyl group, lower alkoxydicarbonyl group, lower alk+
represents a phenyl group which may have 1 to 3 substituents selected from the group consisting of a 2-alkyl group and a hexogen-substituted lower alkyl group. X represents a lower alkyl group which may have a phenyl group as a substituent. ] Carposi acid amide derivatives.