JPS5867669A - Benzamide derivative - Google Patents

Abstract

NEW MATERIAL:The benzamide derivative of formulaI(R1 is H, CH3 or OCH3; R2 is 2-8C alkyl or phenyl; R3 is H or 1-2 CH3; n is 0 or 1). EXAMPLE:3-Propionyl-N-pyridylbenzamide. USE:Drug. It has blood sugar level depressing activity. PROCESS:The compound of formulaIcan be prepared by (1) reacting the 3-nitrobenzoyl halide of formula II (X is halogen) with an amino-pyridine compound of formula V in an inert solvent preferably in the presence of a base such as triethylamine, etc. to obtain the 3-nitrobenzamide derivative of formula III, (2) reducing the product by conventional method, and (3) acylating the resultant 3-aminobenzamide derivative of formula IV with a carboxylic acid halide of formula R2COX.

Description

Detailed Description of the Invention The present invention is based on the following general formula (wherein R1 represents a hydrogen atom, a methyl group, or a methoxy group, and Rfi represents a straight chain or branched @0 alkyl group having 2 to 8 carbon atoms or a substituted phenyl group). (- represents a hydrogen atom or 1 to 2 methyl groups, and the staff represents O゛ or Fi1).

The compound of the present invention represented by the above formula (1) has a hypoglycemic effect and is useful as a medicine.

The compounds of the present invention can be produced, for example, by reacting 3-nitropenzoyl chloride with an amine in the presence of a base to obtain a 3-nitrobenzamide derivative, as shown below, and then converting this into a 3-nitrobenzamide derivative by a conventional method. It can be obtained by acylating it as a benzamide derivative.

The formula for this is as follows. In the formula, X means a halogen atom, and the other 9 and 1 have the same meanings as above.

[I) The reaction between compound CI) and aminopyridines is carried out according to the usual acid oxide formation reaction method, for example, acetone,
The reaction is carried out in an inert solvent such as tetrahydrochloride or dioxane, preferably in the presence of a base such as triethylamine or pyridine, at 0 to 30°C for 1 to 5 hours.

Compound (1) is prepared by a conventional method, for example, palladium-carbon,
Compound (V) can be easily led to compound (V) by a base reaction using a catalyst such as nickel or platinum dioxide.

The reaction between compound (IV) and carbon-chloride is
The reaction is carried out under conventional acid amide formation reaction conditions, for example in an inert solvent such as acetone, tetrahydro7rane or dioxane, preferably in the presence of a base such as triethylamine or pyridine, for 0 to 30 liters, for 1 to 5 hours.

Example 1゜2-Annoviridine 2 & 2f,) ethylamine 45d
In a mixed solution of 600w/acetone and 600w of acetone, 3
-Nitrobenzoyl chloride55. .

Gradually add 8t. 30 minutes at the same temperature, then 1 hour at room temperature.
After stirring for an hour, the reaction solution was poured into 3j- of water, and the precipitated crystals were collected, washed with water, and then recrystallized from methanol to obtain colorless needle-like crystals of 3-nitro-N-2-pyridylbenzamide 5&5.
I got f. Yield SOW.

Hydrogen is passed through a mixture of 15.9f of this (2), 1.5f of 10% palladium-carbon and 300+d of ethanol with a melting point of 156 to 157°C, and catalytic reduction is carried out by a conventional method. After absorbing the calculated amount of hydrogen, the catalyst was removed, the reaction solution was concentrated under reduced pressure, and the residue was recrystallized from ethanol to give colorless needle-like crystals of 3-amino-N.
-Good at 2-pyridylbenzand 7.2f, yield 52
X, melting point 113-115°C, this &4 f, ) To a mixed solution of 45 ml of ethylamine and 60 d of acetone, 2.82 g of propychloride was gradually added while stirring at room temperature. After stirring for 1 hour, the reaction solution is poured into 200 d of water and then made slightly alkaline by gradually adding 10% sodium hydroxide solution. The precipitated crystals were collected, washed with water, and then recrystallized from methanol to obtain colorless needle-shaped 3-propionyl crystals.
N-diylbenzamide (compound 1) 7, Of was obtained. Yield 87%, melting point 128-129°C.

Elemental analysis value Molecular formula als HII N5oz O
HN Theoretical value (2) 66.90 5.61 15.61 Actual value (2) 66.97 5.65 15.52 The compounds shown in Table 1 were obtained in the same manner as in Joki.

Example 2 Group of 5 mice, 5 week old DDY mice (1 male weighs 25-30
? ) was fasted for 16 hours, 75q/kl of azutsuxane was administered intravenously, and 48 hours later, the compound of the present invention (200#9
An aqueous solution or suspension of 150 minutes later was administered orally, and 150 minutes later, blood was collected from the heart and the amount of sugar in the blood was measured by the glucose oxidase method.

The measurement results are illustrated in Table 2.

Note that the compound numbers in the table correspond to the compound numbers of Example 1.

Table 2 Kisr<o, os Kakuden Sr<0.01 Dendenmine SIP<0.001 Continued from page 1 0 Inventor Masuo Koizumi Chugai Pharmaceutical Co., Ltd., 41-8 Takada 3-chome, Toshima-ku, Tokyo 0 Inventor: Yasushi Murakami, Chugai Pharmaceutical Co., Ltd., 3-41-8 Takada, Setshima-ku, Tokyo Inventor: Yoshikazu Hinohara, Chugai Pharmaceutical Co., Ltd., 3-41-8 Takada, Toshima-ku, Tokyo Inventor: Hideki Nakano, Chugai Pharmaceutical Co., Ltd., 3-41-8 Takada, Toshima-ku, Tokyo Inventor: Yoshio Takagaki, Chugai Pharmaceutical Co., Ltd., 3-41-8 Takada, Toshima-ku, Tokyo

Claims (1)

[Claims] General formula (in the formula, R1 represents a hydrogen atom, a methyl group or a methoxy group, Rj represents a straight or branched alkyl group having 2 to 8 carbon atoms or a substituted phenyl group, and R3 represents hydrogen) atoms, or 1-2
Benzamide derivatives represented by ) (indicating 1 digit methyl group and 1 digit 0 digit l).