JPS596850B2 - Propanol derivatives and their production method - Google Patents

Description

[Detailed Description of the Invention] The present invention relates to the general formula (wherein R^'' and R^2 have the same meaning as above)
It can be produced by reacting the oxirane derivative [■] represented by the formula with the compound [■] represented by the formula.

This reaction can be carried out using compound [■] as both a reagent and a solvent, or can also be carried out in an appropriate solvent. The reaction is preferably carried out at room temperature to about 100° C. with stirring, and compound [I] can be obtained in high yield. Note that the starting compound [■] can be produced, for example, by the method shown in the following reaction formula.

Examples of such acid addition salts include salts with inorganic acids such as hydrochloric acid, phosphoric acid, nitric acid, and sulfuric acid, or acetic acid, lactic acid, citric acid, tartaric acid, fumaric acid, maleic acid, glycine, aspartic acid, methanesulfonic acid, These include salts with organic acids such as benzoic acid.

(However, R1 and R2 have the same meanings as above.) A method for producing a propanol derivative or a pharmacologically acceptable acid addition salt thereof. (However, X represents a halogen atom, and R1 and R2 have the same meanings as above. have the same meaning.

) The compound [1] of the present invention can be used as a medicine as a free base and is medically acceptable. where R2 represents a lower alkoxy group.

) and its production method.

Compounds [1] of the present invention are all new compounds, have central depressant action, and are useful pharmaceutical compounds as tranquilizers, sedatives, and antiemetics.

Examples of the compound of the present invention represented by the general formula [] include lower aliphatic groups in which the group represented by the symbol R1 is a formyl group, an acetyl group, a propanol group, a sometimes branched butyryl group, and a valeryl group. Examples include compounds in which the group represented by the symbol R2 is a lower alkoxy group such as a methoxy group or an ethoxy group, which is an acyl group. The compound [1] of the present invention is an oxirane derivative [] represented by the general formula (wherein R1 and R2 have the same meanings as above) and a compound [] represented by the formula
It can be produced by reacting with.

This reaction can be carried out using the compound [ ] as both a reagent and a solvent, or can also be carried out in an appropriate solvent. The reaction is preferably carried out at room temperature to about 100° C. with stirring, and the compound [ ] can be obtained in high yield. Note that the starting compound [] can be produced, for example, by the method shown in the following reaction formula.

As a method of administration, it may be administered orally in an appropriate dosage form such as powder, tablet, capsule, solution, emulsion, or suspension.
or administered parenterally.

Experimental Example 1 Group of 5 male mice were given 1-(4-acetamido-2-methoxyphenoxy)-3-(4-phenylpiperidino)-
2-propanol was administered intraperitoneally, and the following effects were investigated.

The results were as shown in Table 1. (1) Maximum tolerance This was determined based on the presence or absence of death 48 hours after administration of the sample.

(2) Spontaneous movement suppression effect 30 minutes after administration of the sample, the amount of movement was measured using Animex for 5 minutes, and when the amount of movement was suppressed to 1/2 or less of the control group, it was determined to be effective, and the ED5O value was determined.

(3) Anesthesia-enhancing effect 30 minutes after administration of the sample, methylhexavitanosodium (100η/K9) is administered intraperitoneally. If the righting reflex disappearance time is at least twice that of the control group, it is judged to be effective. The ED5O value was determined.

(4) Anti-apomorphine effect 30 minutes after administration of the sample, apomorphine hydrochloride (2.5η/K
9) was administered subcutaneously, and the ED5O value was determined using the inhibition of the cage climbing reaction as an index.

Example 1 3-(4-acetamido-2-methoxyphenoxy)-1
・2-epoxypropane 1.07 to ethanol 30ml
742η of 4-phenylpiperidine was added thereto, and the mixture was stirred at 90°C for 4 hours.

When ethanol is distilled off and the residue is recrystallized from ethyl acetate, 1-(4-acetamido-2-methoxyphenoxy) is obtained.
1.387 was obtained as a powder crystal of -3-(4-phenylpiperidino)2-propanol. Yield: 82.1% M. p. l64-165.5℃

Claims (1)

[Claims] 3. General formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ [II] (However, R^
1 represents a lower aliphatic acyl group, and R^2 represents a lower alkoxy group. ) is reacted with a compound represented by the formula ▲ ▼ There are mathematical formulas, chemical formulas, tables, etc. ▼ [III], and then, if desired, the product is converted into its pharmacologically acceptable acid addition salt. A propanol derivative or its pharmacologically acceptable acid addition salt represented by the characteristic general formula ▲ Numerical formula, chemical formula, table, etc. ▼ (However, R^1 and R^2 have the same meanings as above.) manufacturing method.