JPS59175467A - Ureidobenzamide derivative - Google Patents

Abstract

NEW MATERIAL:An ureidobenzamide derivative shown by the formula I (R1 is H, lower alkyl, or lower alkoxy; R2 is H, halogen, lower alkoxy, or 1-2 lower alkyl; n is 0 or 1). EXAMPLE:3-Ureido-N-2-pyridylbenzamide. USE:A drug having blood sugar lowering action. PREPARATION:For example, a 3-nitrobenzoyl chloride shown by the formula IIis reacted with an amine in the presence of a base, to give a 3-nitrobenzamide derivative shown by the formula III, which is then reduced to give a 3-aminobenzamide derivative shown by the formula IV, which is reacted with an alkali cyanate in an acidic aqueous solution, to give the desired compound shown by the formula I .

Description

Detailed Description of the Invention The present invention relates to the following general formula (wherein R1 represents a hydrogen atom, a lower alkyl group, or a lower alkoxy group, and R2 represents a hydrogen atom, a hydrogen atom, a lower alkoxy group, or 1 to 2 a group, n is 0 or 1
shows. ) is related to the ureidobenzamide m2i form.

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

The compound of the present invention can be produced, for example, by reacting 3-nitrobenzoyl chloride with an amine in the presence of a base to obtain a 3-2F lobenzamide derivative as shown below, and then reducing this by a conventional method to form a 3-aminobenzamide. It can be obtained by making it into a derivative and then reacting it with an alkali cyanate in an acidic water bath.

The formula for this is as follows. In addition, in the formula, X is
The halogen atom and A mean an alkali metal atom, and the other symbols have the same meanings as above.

[■] [Dish] Reaction between compound CIIJ and aminopyridine angle +1, j1
a It is carried out under conventional acid amide formation reaction conditions, e.g.
The reaction is carried out in an inert solvent such as acetone, tetrahydrofuran, diquine, etc., or in the presence of a base such as triethylamine, pyridine, etc. at 0 to 30° C. at 1 to 5 o'clock No. II.

Compound [■] can be easily converted into compound [■] by a conventional method, for example, by a reduction reaction using a catalyst such as noradium-carbon, Raney nickel, or platinum dioxide.

The reaction between compound [■] and cyanate is carried out under the usual urea formation reaction conditions. For example, compound (■) is dissolved in an acidic water bath solution such as hydrochloric acid or acetic acid, then an alkaline cyanate bath solution is added, and the It is carried out at 100°C for 1 to 5 hours.

Example 1゜2-aminopyridine 28.2f,) ethylamine 45
3-nitrobenzoyl chloride was gradually added to a mixed bath solution containing 600 mg of acetone and 600 mg of acetone. The precipitated crystals were collected, washed with water, and then recrystallized from methanol to obtain 58.57 ml of 3-nitro-N-2-pyridylbenzamide in the form of colorless needles. Yield: 80%.

Melting point: 156-157°C. Hydrogen was passed through this mixture of 15.9 f, 10% palladium-carbon 1.51 and 300 ytt of ethanol, and catalytic reduction was 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 0;
3-Amino-N-2-py1)zylbenzamide 7.2
L? I got it. Yield 52%, melting point 113-115°C. Dissolve this 6.42 in 50 ml of 5% hydrochloric acid solution, press down at room temperature, make alkaline by adding an excess of 10% cyanic acid, and continue stirring for 21 hours at the same temperature. Precipitation. The resulting crystals were separated, washed with water, and then recrystallized from methanol to obtain colorless needle-like crystals of 3-ureido-N-2-pyridylbenzamide (Ishi compound I) at a yield of 5.57. Yield: 72%.
Melting point 223-224°C.

Elemental analysis value Molecular formula 013 HI3 N4 0 as o2 ) I N J Fu j1 i Lun I Direct σ Gong 60.93 4
．． 72 2],, 87 real 1jll value (M 6
0.90 4.75 21.88'' - The compound shown in Table 1 was obtained in the same manner as described above.

Example 2 After fasting for 16 hours, 1gY-5 5-week-old DDY mice (iIf, weight 25-30S') were treated with alloxan 75.
prg/kg was administered intravenously, 48 hours later, a water bath solution or suspension of the compound of the present invention (20011rg/#) was orally administered, and 150 minutes later, blood was collected from the heart and the blood sugar level was determined by the glucose oxidase method. was measured.

The measurement results are illustrated in Table 2.

Note that the compound numbers in the table correspond to compound No. 917 of Example 1.

Claims (1)

[Claims] NH0NH2 (in the formula, R1 represents a hydrogen atom, a lower alkyl group, or a lower alkoxy group, and R2 represents a hydrogen atom, a halogen atom, a lower alkoxy group, or 1 to 2 lower alkyl groups) ,n
indicates 0 or 1. ) A ureidobenzamide derivative represented by