JPS6310703B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to a novel phalnesyl acetate amide compound or a salt thereof in which the amine residue is a substituted or unsubstituted piperazino group, and the compound is represented by the following general formula (). In formula (), R represents a hydrogen atom, an alkyl group or an alkenyl group. The above compounds may be in the form of salts that amine nitrogen-containing compounds normally take, such as hydrochlorides, hydrobromides, sulfates, phosphates, citrates, and quaternary ammonium salts. The phalnesyl acetate amide compound or its salt provided by the present invention generally exhibits strong antibacterial activity and is therefore useful as a preservative, disinfectant, and bactericidal agent. It also exhibits antiulcer activity and is useful as a peptic antiulcer agent. can be expected. Furthermore, the salts of the compounds have good affinity for water and organic substances and can be used as surfactants and wetting agents. In the general formula (), the alkyl group represented by R is, for example, a methyl group, an ethyl group, an isopropyl group, n
-propyl group, n-butyl group, n-pentyl group,
These include n-octyl group, n-decyl group, etc. Examples of the alkenyl group represented by R are vinyl group, prenyl group,
These include geranyl group and farnesyl group. Preferably, the number of carbon atoms in these hydrocarbon groups does not exceed 15. The piperazine ring-containing pharnesyl acetate amide compound of the present invention can be produced by various known methods for producing carboxylic acid amides, except for using the corresponding starting materials. The most common method is the following formula () [In the formula (), X represents a group that can react with an amino group to produce an amide, such as OH, a halogen atom, or an alkoxy group], or a reactive derivative thereof, and the following formula () This is a method of reacting with a piperazine compound represented by [Formula (), R has the same meaning as in Formula ()]. When the amide compound of formula () produced by this reaction is reacted with a mineral acid, an organic acid, or an alkyl halide, a corresponding salt including a quaternary ammonium salt is obtained. Examples of the phalnesyl acetate amide compound and its salt of the present invention are listed below, and the compound number will be used hereinafter to refer to the compound. In the formula, F is a farnesyl group G is geranyl group

[Formula] P is preni group

[Formula] means. (1)

[Formula] and HCl salt, HBr salt (2)

[Formula] and HCl salt, HBr salt (3)

【formula】 (Four)

【formula】 (Five)

[Formula] and HCl salt, HBr salt (6)

[Formula] and HCl salt, HBr salt (7)

[Formula] and HCl salt, HBr salt (8)

[Formula] and HCl salt, HBr salt As mentioned above, the falnesyl acetate amide compound and its salt of the present invention have anti-ulcer effects, and some are falnesyl acetate geranyl ester (gefalnate), which is widely used as an anti-ulcer agent.
Shows significantly higher activity. An example is given below. After fasting male Dongliu rats (210-230 g) for 24 hours, indomethacin (manufactured by Merck & Co.) was administered subcutaneously in the form of a suspension in 1% CMC solution in an amount of 20 mg/Kg. Seven hours later, the rats were sacrificed with ether, and the length (mm) of indomethacin-induced ulcers that had developed on the gastric mucosa were measured. The total length of ulcers per animal is the ulcer coefficient. The test compound and gefalnate were tested after administration of indomethacin.
Each was orally administered 10 minutes before. The inhibition rate was calculated by dividing the difference in ulcer coefficient between the control group and the sample administration group by the ulcer coefficient of the control group. The results are shown in Table 1.

[Table] Furthermore, as mentioned above, the compounds of the present invention and their salts have antibacterial activity and are useful as components of disinfectants, preservatives, or agricultural and horticultural fungicides, but they also have surfactant activity. Therefore, it is suitable as an ingredient in soaps, shampoos, and conditioners. A test example of antibacterial activity is shown below. The compound of the present invention was diluted with acetone to obtain a solution of a predetermined concentration, and the solution was soaked into a paper disk having a diameter of 8 mm. Agar plate containing bacteria after leaving the disk to completely remove acetone
placed on top. 30℃ for test bacteria Psl and X;
The radius (mm) of the inhibition circle observed after culturing each strain for 24 hours and at 37°C for 24 hours for other test bacteria was measured. The results are shown in Table 2. The test bacteria indicated by abbreviations in the table are as follows. Test bacterium a: Staphylococcus. Aureus FDA
209 (Staphylococcus aureus FDA 209
P) s: Bacillus. Bacillus subtilis IAM 1069 (Bacillus
sub.IAM 1069) c: Ethelicia. Cori IAM 1239 (Eschelichia
coli IAM 1239) Sal: Salmonella. Typhimurium IFO 12529
(Salmonella typhimurium IFO 12529 Ps: Pseudomonas aeruginosa AKV 823
(Pseudomonas aernginosa AKV 823) Er: Erwinia. Eloide E-705 (Erwinia
aroideae E-705) Psl: Pseudomonas. Pseudomonas lachrymans X: Xanthomotos. Oryzae (Xanthomonas)
oryzae)

[Table] Example 1 55.6 g of methyl pharnesyl acetate and 20 g of anhydrous piperazine were placed in a three-neck flask equipped with a thermometer and a stirrer, heated to 160° C., and reacted for 5 hours.
After the reaction is completed, it is separated by preparative liquid chromatography (Waters System 500).
28 g of monophalnesylacetylpiperazine was obtained. The structure of the product was confirmed by proton NMR and mass spectrometry. The NMR data is shown below.

【table】

[Table] Examples 2 to 4 Using methyl pharnesyl acetate and the amines shown in Table 3, reactions and post-treatments were carried out in the same manner as in Example 1 to synthesize the corresponding pharnesyl acetate amide compounds. The hydrochloride was prepared by reacting the obtained amide compound with 1N hydrochloric acid. The results are shown in Table 3.

[Table] NMR data example 2 [Compound (2)] (δ in CDCl ₃ 90NHz) 1.52 (s) and 1.59 (s) 12H 1.80-2.05 (m) 8H 2.15-2.40 (m) 11H 3.25-3.65 (m) ) 4H 4.85-5.20 (m) 3H Example 3 [Compound (6)] (δ in CCl ₄ 90MHz) 1.50-1.80 (m) 18H 1.80-2.05 (m) 8H 2.10-2.20 (m) 4H 2.25, 2.31, 2.37 (t) 4H 2.82, 2.90 (d) 2H 3.26-3.58 (m) 4H 4.85-5.25 (m) 4H Example 4 [Compound (7)] (δ in CCl ₄ 90MHz) 1.55 (s) and 1.62 (s ) 21H 1.85-2.10 (m) 12H 2.10-2.20 (m) 4H 2.20, 2.26, 2.32 (t) 4H 2.80, 2.80 (d) 2H 3.25-3.55 (m) 4H 4.85-5.28 (m) 5H Example 5 Implementation N-methyl synthesized in the same manner as Example 2
10 g of N'-phalnesylacetylpiperazine and 10 g of ethyl bromide were reacted in 100 ml of acetonitrile under reflux for 10 hours. After the reaction was completed, unreacted ethyl bromide and acetonitrile were distilled off.
11.6 g of pale yellow solid was obtained. This thing is
It was confirmed to be compound (4) by NMR and elemental analysis. The NMR data is shown below.

【table】

Claims (1)

[Claims] 1. The following general formula () [R in formula () represents a hydrogen atom or an alkyl group or alkenyl group having 15 or less carbon atoms]
A falnesyl acetate amide compound having a piperazine ring or a salt thereof. 2. The salt of a falnesyl acetate amide compound according to claim 1, wherein the salt is a hydrochloride or a hydrobromide. 3. The salt of a falnesyl acetate amide compound according to claim 1, wherein the salt is a quaternary ammonium salt.