JPS6239565A - Succinimide derivative - Google Patents

Abstract

NEW MATERIAL:A succinimide derivative expressed by formula I (R is dihalogen-substituted phenyl, lower alkoxy-substituted phenyl, styryl, biphenylyl or naphthyl). EXAMPLE:N-(4-Methoxyphenylmethyl)succinimide. USE:An antiulcer agent capable of exhibiting improved inhibitory action on stress ulcer. PREPARATION:For example, succinimide expressed by formula II is condensed with a compound expressed by the formula R-CH2-X (X is halogen), in the presence of a base to afford the aimed compound expressed by formula I.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to novel cono-phosphate imide derivatives. That is, the present invention provides a novel compound represented by the general formula: [wherein R represents a civaloquine-substituted phenyl group, a lower alkoxy-substituted phenyl group, a styryl group, a biphenylyl group, or a naphthyl group].

The compound represented by the above formula (1) exhibits an excellent stress ulcer suppressing effect and can be used as a pharmaceutical useful as an anti-ulcer agent.

The present invention will be explained in detail below.

First, to explain the novel compound according to the present invention, as an example of a compound represented by formula (1), in general formula (1), R is 2,4-dichlorophenyl, 5.41chlorophenyl 2.6- Examples include compounds which are a phenyl group substituted with chizino-rogen such as dichlorophenyl; a lower alkoxy-substituted phenyl group such as 4-methoxyphenyl; a styryl group; a biphenylyl group such as 4-biphenylyl; or a naphthyl group such as 1-naphthyl.

Next, a method for producing the compound of formula (1) according to the present invention will be described.

The compound represented by the general formula (1) of the present invention is, for example,
It can be manufactured by the following method.

1) Cleavage method 1: Succinimide represented by the formula and the general formula R-CH2-X
(3) Produced by subjecting the compound [wherein R has the meaning as defined in formula (1) above and X represents a halogen atom] to a condensation reaction in the presence of a base. Can be done.

2) Production method 2 Succinic anhydride shown in the formula (2) and a compound of the general formula, R-CH2-NH2(5) [wherein R has the meaning as defined in the above formula (1)] It can be produced by reacting.

The compound of formula (1) according to the invention can be used as an anti-ulcer agent. This product can be administered in the form of capsules, tablets, lozenges, suspensions or emulsions. These various preparations are manufactured by conventional methods.

The dosage of the active compound is determined appropriately depending on the patient's age, weight, symptoms, etc., but the daily dosage is usually 101
The amount is from g to 1000JI9.

Next, the method for producing the compound of formula (1) according to the present invention will be explained with reference to Examples.

Example 1 A mixture of 424J1g of N-(4-methoxyphenylmethyl)conophosphate succinimide, 10-1 potassium carbonate 731Q of N,N-dimethylformamide, and 548mg of 4-methoxybenzyl chloride was heated at 100°C.
The mixture was stirred for 10 hours. The reaction solution was concentrated under reduced pressure, ethyl acetate was added thereto, washed with water, and then dried over anhydrous sodium sulfate. After evaporating the solvent under reduced pressure, the remaining crystals were recrystallized from ethyl acetate-hexane to obtain 576 jg of the title compound.

Melting point 127.6-128.8°C Mass spectrum (m/e): 219 (M”)
, 191.190.

176, 160, 148, 134, 121,
55 Examples 2 to 7 By the reaction procedure based on Example 1, using succinimide and the corresponding chloride for each compound, the following Table 1 was prepared.
Each compound listed therein was manufactured.

In Table 1, the compounds obtained in each example are represented by R in formula (1).
The melting point and mass spectrum of the compound are listed.

Table 1 56.55 3 3.4-Jik 1:10 140.0-141.0
°C rx4; 261,259,257 (M+5° phenyl 196,194
,56,55141.56.55 5 Styryl 141.5-143.5℃ i;215
(M+), 116. η5゜ioo, ss 6 4-biphenylyl 147.8-149. D.C.
Ve: 2'65 (M"), 237,236°180.1
65.55 7 1-Naphthyl 97.0-101.0℃ Inpuku;
239 (M+), 210,154° Tests regarding the stress ulcer suppressing effect were conducted on the compounds according to the present invention. Test examples and data are shown below.

Test method Stress ulcer suppression effect by water immersion restraint Takagi, Sobe et al.: Jap, J, Pharmacol
18, 9 (1968), the test compound was orally administered to male Wistar rats weighing around 240 P after fasting for 18 hours. After 60 minutes, the rats were placed in stress cages and immersed up to their chests in a water bath at 25±1° C. to be stressed. After 6 hours, the rats were killed and
Then, the helmet was removed and 10-mL physiological saline was injected. After fixation with 5% formalin for 5 minutes, the stomach was incised along the major groove, and the long axis of the ulcer observed in the glandular stomach was measured, and the sum total was taken as the ulcer index per animal. The test compound was suspended in a solution of gum arabic, and
It was administered orally at a rate of y. The antiulcer effect thus obtained was calculated using the following formula and is shown in Table 2 as the average value for 9 to 10 animals per group.

Suppression rate (4) = [((ulcer coefficient of control group) - (
Ulcer coefficient of each group)) ÷ (Ulcer coefficient of control group)) xloo Test result table 2 176□□□) 559* 665$ Note: Umbrella 5011VkII administration

Claims (1)

[Claims] Formula: ▲There are mathematical formulas, chemical formulas, tables, etc.▼ [In the formula, R represents a dihalogen-substituted phenyl group, a lower alkoxy-substituted phenyl group, a styryl group, a biphenylyl group, or a naphthyl group] Succinimide derivative.