JPS5929594B2 - alcohol derivative - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention is based on the general formula ゛'C゛もhe~■~ [I] (wherein, R'' is hydrogen, . . . , halogen, R2 is hydrogen, lower alkyl, halogen, A represents lower alkylene, B represents CH or N, and X represents hydrogen or lower alkylcarbonyl.

) or its acid addition salt.

In the above definition, lower alkyl refers to methyl, ethyl, etc.
・Rogen refers to chlorine, bromine, fluorine, 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 H-l-CH2Co□A-O-X0l [wherein R1, A, and X are as defined above, and Hal is...
・Indicates rogens (chlorine, bromine, etc.).

] and the general formula 0 [■] (wherein, R2 has the same meaning as above, and Y represents amino or methyl.

) is produced by reacting with the compound represented by

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

At that time, a compound of the general formula [] is used as a deoxidizing agent.
It is also possible to use twice the molar amount of the compound, or to add sodium bicarbonate, sodium carbonate, potassium carbonate, sodium hydroxide or potassium hydroxide. Also, general formula [
The compound in which X is hydrogen in 1] is produced by hydrolyzing a compound in which X is lower alkylcarbonyl.

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

Furthermore, the compound of the general formula [1] is a compound of the general formula (wherein R1, R
2. B has the same meaning as above, R4 represents hydrogen, lower alkyl, or lower alkoxy, and z represents a single bond or lower alkylene.

) can also be obtained by subjecting the compound represented by formula to a reduction reaction.

When R4 is hydrogen or lower alkyl, the reaction is carried out using sodium borohydride in a solvent such as methanol or ethanol, and when R4 is lower alkoxy, the reaction is carried out using, for example, lithium aluminum hydride in tetrahydrofuran. Alternatively, sodium bis(2-methoxyethoxy)aluminum hydride may be used in a solvent such as benzene or toluene.

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 converted into an acid addition salt by a conventional method.

As is clear from the following experiments, the compound of general 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)
The method of rschOt et al. [J. PharmaOl. ex
p. Ther. , vol. 125, p. 237 (1957)
].

The test compound was orally administered to female Dd mice (6 mice per group) weighing around 20f7, and 1 hour later, 0.2% phenylquinone solution was administered intraperitoneally at 0.2ml/20r, and then 2
The frequency of 0-minute stretch symptoms was observed, and the ED5O value was determined from the inhibition rate relative to the control group using the propit method. Experimental method 2 Anti-inflammatory effect (ultraviolet erythema method) Winder et al.'s method [Arch. int. Pharm
acOdyn. ．． ll6 volume 261 page (1958)
].

Using guinea pigs weighing 250 to 4,507 kg, a rubber plate with three holes of 7 m 7 nm in diameter was applied to the flanks of which hair had been removed in advance, and irradiated with a 600 W mercury lamp from a distance of 15 CfL for 80 seconds. After 2 hours, the degree of erythema formation was reduced to Win.
Scoring was performed according to the scoring method of der et al., and the total score was 1.
．． A value of 5 or less was considered effective, and the effectiveness rate was calculated.

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 (carrageenin method) Winter et al.'s method [PrOc. SOc. Exptl
．． BlOl. Med. Volume llll, page 544 (1971
2000)].

The test compound solution was orally administered (25 ml/K9) to DOnryu rats (5 rats per group) weighing around 1,507 kg, and 1 hour later, 0.05 ml of 1% carrageenan was injected subcutaneously into the right hind paw, and after a certain period of time, the paw volume was The percentage of increase in the paw volume before carrageenan administration was calculated, and the inhibition rate was determined 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 compounds A and B in the table are as follows.

A: 2-[4-(imidazo[1.2-a]pyridine-2
-yl)phenyl]-1-propanol B:2-[4-
(Imidazo[1,2-a]pyridin-2-yl)phenyl]propyl acetate When the compound of the general formula [1] or its acid addition salt is used as a medicine, it may be used as a pharmaceutical compound or in an appropriate pharmacologically acceptable carrier. , excipients, and diluents, and can be administered orally or parenterally in the form of powder, granules, tablets, capsules, suppositories, injections, and the like. The dosage varies depending on the symptoms, etc., but is 50-1507
r9 is preferred. EXAMPLES The present invention will be specifically described below with reference to Examples.

Example 1 4-(chloroacetyl)phenethyl acetate 48y and 2-aminopyridine 237 were dissolved in ethanol 200ml
and heated under reflux for 4 hours.

Ethanol is distilled off under reduced pressure, 100 ml of water and 20 t of sodium hydrogen carbonate are added to the residue, and the mixture is heated on a water bath for 1 hour.
The reaction solution is extracted with ethyl acetate, washed with water, dried over magnesium sulfate, and concentrated under reduced pressure to obtain a brown oil. Add a small amount of ethyl acetate to this and remove the precipitated crystals.
It is then recrystallized from ethyl acetate to give a melting point of 102-10.
4-(imidazo[1.2-a] is a colorless crystal at 5°C.
Pyridin-2-yl)phenethyl acetate 357 is obtained. Example 2 Dissolve 23V of 4-(imidazo[1,2-a]pyridin-2-yl)phenethyl acetate in 100ml of ethanol, add alkaline water (4V of sodium hydroxide, 20ml of water), and leave at room temperature for 10 minutes. .

Concentrate under reduced pressure, add water to collect the precipitated crystals, and recrystallize from ethyl acetate to obtain 4-[imidazo(1,2-a)pyridine-, which is a colorless crystal with a melting point of 132-134°C.
15 t of 2-yl]phenethyl alcohol are obtained. Example 3 4.2 t of 4-(imidazo[1,2-a]pyridin-2yl)acetophenone was suspended in 50 ml of methanol, 1.0 t of sodium borohydride was added little by little under ice cooling, and the mixture was stirred for 30 minutes. Reflux.

Concentrate under reduced pressure, add ice water and collect the precipitated crystals,
Recrystallization from methanol yields 2.8 tons of 1-[4-(imidazo[1.2-a]pyridin-2-yl)phenyl]ethanol as colorless crystals with a melting point of 214-215°C. Example 4 3.8 t of lithium aluminum hydride was added to 100 ml of tetrahydrofuran, and while stirring under ice cooling, 2-[
A solution of 29.4 t of 4-(imidazo[1.2-a]pyridin-2-yl)phenyl]propionic acid ethyl ester (melting point 112-114°C) dissolved in 200 ml of tetrahydrofuran is added dropwise at a temperature below 10°C.

Claims (1)

[Claims] 1 General formula ▲ Numerical formula, chemical formula, table, etc. ▼ (In the formula, R^1 represents hydrogen or halogen, R^2 represents hydrogen, lower alkyl, or halogen, A represents lower alkylene, B represents CH or N, X represents hydrogen or lower alkylcarbonyl) or an acid addition salt thereof.