JPS5940835B2 - alcohol derivative - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION In the general formula of the present invention, A represents lower alkylene, and X represents hydrogen or lower alkylcarbonyl.

) or its acid addition salt.

In the above definition, lower alkyl refers to methyl, ethyl, etc., and lower alkylene refers to methylene, ethylene, trimethylene, propylene, etc.

According to the present invention, the compound represented by the general formula (I) has the general formula Hal-CH2COOA-O-X (■) [wherein A
, X have the same meanings as above, and Hal represents halogen (chlorine, bromine, etc.).

It is produced by reacting a compound represented by ] with a compound represented by the formula NH2 (■).

The reaction is preferably carried out in an alcoholic solvent such as methanol or ethanol under reflux.

At that time, the compound of formula (■) is used as a deoxidizing agent.
Although twice the molar amount of the compound is used, sodium hydrogen carbonate, sodium carbonate, potassium carbonate, sodium hydroxide, or potassium hydroxide may be added. Further, a compound in the general formula (I) in which x is hydrogen is produced by hydrolyzing a compound in which X is lower alkylcarbonyl.

This reaction is carried out under acidic conditions (hydrochloric acid, hydrobromic acid, sulfuric acid, etc.) or preferably under basic conditions (sodium hydroxide,
potassium hydroxide, etc.).

Furthermore, the compound of the general formula (I) can be prepared by the general formula R- (wherein R is hydrogen, lower alkyl, lower alkoxy,
Z represents a single bond or lower alkylene.

) can also be obtained by subjecting the compound represented by formula to a reduction reaction. For the reaction, when R is hydrogen or lower alkyl,
For example, by using sodium borohydride in a solvent such as methanol or ethanol, or if R is lower alkoxy, using lithium aluminum hydride in tetrahydrofuran, or by hydrogenation in a solvent such as benzene or toluene. It is carried out using sodium bis(2-methoxyethoxy)aluminum.

Compounds of general formula (1) having an asymmetric carbon can usually be separated into optically active enantiomers by well-known methods.

The compound of general formula (1) can be subjected to acid addition using a conventional method.

As is clear from the following experiments, the compound of Ikkoku formula (1) has analgesic, antipyretic, and antiinflammatory effects, and is useful, for example, as an analgesic and antiinflammatory agent, and as a synthetic intermediate thereof.

Next, the pharmacological action of the compound of general formula (1) will be shown together with experimental methods.

Experimental method 1 Analgesic effect (phenylquinone method) HendergchOt et al.'s method [J. Pharmac
Ol. exp. Ther. , vol. 125, p. 237 (1
957)].

The test compound was orally administered to female Dd mice (group of 6 mice) weighing around 20 y, and 1 hour later, 0.02% phenylquinone solution was administered intraperitoneally at 0.2 ml/20 y, and the frequency of stretching symptoms was observed for 20 minutes thereafter. The ED5O value was determined from the inhibition rate with respect to the control group by the propitt method. Experimental method 2 Anti-inflammatory effect (ultraviolet erythema method) Winder et al.'s method [Arch. int. Pharm
acOdyn. Volume ll6, page 261 (1958)]
I went to bed.

Using a guinea pig weighing 250 to 450 years, a diameter of 7 m7 is placed on the flank that has been previously depilated. f) Place a rubber plate with 3 holes on it and use a 600W mercury lamp for 15? 8 from a distance of
Irradiated for 0 seconds. After 2 hours, reduce the degree of erythema formation.
Scoring was performed according to the scoring method of er et al., and the total score was 1.
A value of 5 or less was considered effective, and the effectiveness rate was determined.

In addition, half the test compound solution was added one hour before and immediately after irradiation (
The total amount was 10 ml/Kg) orally. Experimental method 3 Anti-edema effect (carrageenan method) Winter et al.'s method [PrOc. SOc. Exptl
．． BiOl. Med. Volume llll, page 544 (1971
2000)].

DOnr37U rats weighing around 1507 kg (5 rats per group)
The test compound solution was orally administered (25 ml/Kg), and 1 hour later, 0.05 ml of 1% carrageenan was subcutaneously injected into the right hind paw, and the paw volume was measured after a certain period of time to determine the increase in paw volume from before carrageenan administration. The percentage was calculated to determine the inhibition rate relative to the control group. This inhibition rate was shown as the average value of 2 to 3 repeated experiments. The results of the above experiments are summarized in Table 1 as follows. Test compound A in the table is as follows.

A: 2-[4-(imidazo[2.1-b]thiazole-
6-yl)phenyl]-1-propanolet general formula (1
) or its acid addition salt is used as a medicine, either by itself or in a suitable pharmaceutical form, mixed with acceptable carriers, excipients, and diluents, and prepared into powders, granules, tablets, capsules,
It can be administered orally or parenterally in the form of suppositories, injections, etc.

Although the dosage varies depending on the symptoms, it is preferably 50 to 150 doses. The present invention will be specifically explained below with reference to Examples.

Example 1 2-(4-chloroacetylphenyl)propyl acetate 127y and 2-aminothiazole 10y were mixed with alcohol 100TII. 1 and heated under reflux on a water bath for 4 hours.

The alcohol is concentrated under reduced pressure, extracted with 200 ml of ethyl acetate, washed with water, and dried over magnesium sulfate. When the crystals obtained by concentrating under reduced pressure are recrystallized from isopropanol, 2-
8.07 of [4-(imidazo[2.1-b]thiazol-6-yl)phenyl]propyl acetate is obtained.
Example 2 2-[4-(imidazo[2.1-b]thiazole-6-
8.07 g of phenyl]propyl acetate is added to 50 ml of alcohol, 10 ml of 20% sodium hydroxide solution is added thereto, and the mixture is allowed to stand at room temperature for about 1 hour.

Concentrate under reduced pressure, collect a lot of the formed crystals, wash with water, and recrystallize from alcohol to obtain 2-[4-(imidazo[2,1-b]thiazole), which is a colorless needle crystal with a melting point of 176-178°C. -6-yl)phenyl]-1-propanol 4.5
7 is obtained. Example 3 4-(imidazo[2.1-b]thiazol-6-yl)
Phenyl ethyl acetate 8.67 to tetrahydrofuran 20
Lithium aluminum hydride solution dissolved in 0ml
．． 37 was suspended in 50 ml of tetrahydrofuran and added dropwise under ice cooling.

After being kept at room temperature for about 1 hour, it is heated under reflux on a water bath for 1 hour.
The reaction solution is ice-cooled, and a saturated aqueous solution of Rothsell's salt is added dropwise to decompose excess lithium aluminum hydride. The tetrahydrofuran layer was separated, concentrated under reduced pressure, and the resulting crystals were recrystallized from isopropanol to give a melting point of 144-145.
4.5y of 4-(imidazo[2.11b]thiazol;ru-6-yl)phenethyl alcohol at a temperature of 4.5y is obtained. below,
The following compounds are synthesized in the same manner.

Claims (1)

[Claims] 1 Alcohol derivatives or acid addition salts thereof represented by the general formula ▲ Numerical formulas, chemical formulas, tables, etc. ▼ (In the formula, A represents lower alkylene and X represents hydrogen or lower alkyl carbonyl.) .