JPS58150591A - Novel thienylimidazole derivative and its preparation - Google Patents

Abstract

NEW MATERIAL:A compound shown by the formulaI(R<1> is 1-5C alkyl, or 2-5C alkenyl; R<2> is halogenophenyl). EXAMPLE:2-(4-Fluorophenyl)-4-(3-thienyl)-5-methylimidazole. USE:An antiphologistic, an anodye, and an antipyretic. PROCESS:For example, a compound e.g., N-(4-fluorobenzoyl)-(3-thienylcarbonyl) methlyamine, etc. shown by the formula II is reacted with a halide compound (e.g., methyl iodide, etc.) shown by the formula R<1>X(X is halogen) at -50-30 deg.C in the presence of an acid acceptor (e.g., sodium hydride, etc.) in a solvent such as THF, etc. to give a novel methylamine compound e.g., N-(4-fluorobenzoyl)-1- (3-thienylcarbonyl)ethylamine, etc. shown by the formula III, which is reacted with ammonium (salt) (e.g., ammonium acetate, etc.), and, if necessary, it is made into a salt.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to novel chenylimidazole derivatives, processes for their production, and pharmaceutical compositions containing them.

JP-A-37-10379 discloses that 2-phenyl-4,5-substituted imidazole derivatives such as 2-(4-bromophenyl)-4-(2-chenyl)-5-methylimidazole have anti-inflammatory effects. It is stated that. However, this 2-(4-bromophenyl)-4-(2-
(chenyl)-5-methylimidazole does not yet have sufficient activity to be used as an anti-inflammatory agent.

As a result of various studies, the present inventors have discovered a novel chenylimidazole derivative having excellent anti-inflammatory, analgesic, and antipyretic effects.

That is, the present invention is based on the general formula: [wherein R1 is a straight chain or branched alkyl group having 1 to 5 carbon atoms or a straight chain or branched alkenyl group having 2 to 5 carbon atoms, and R2 means a halogenophenyl group] The present invention provides novel chenylimidazole derivatives and pharmaceutically acceptable salts thereof.

For example, 2-(4-chlorophenyl)-4-(3-chenyl)-5-ethylimidazole, 2-(4-chlorophenyl)-4-(3-chenyl)-5-(2-n-propenyl)imidazole, 2-(4-fluorophenyl)
- Anti-inflammatory against carrageenin-induced edema in rats for 4-(3-chenyl)-5-ethylimidazole or 2-(4-fluorophenyl)-4-(3-chenyl)-5-(2-n-propenyl)imidazole When we investigated the effect, we found that commercially available thiaramide (chemical name: 4-C)
10 to 5-chloro-2-oxo-3-benzothiazolinyl)acetylcy (1-piperazineethanol)
It has been found to be 30 times more powerful.

Additionally, the Randall Sellitto method (Arch, int.

Pharmacodyn, 1957 +CXI, /P
The analgesic effect of oral administration of 2-(4-fluorophenyl)-4-(3-chenyl)-5-(2-n-propenyl)imidazole was found to be approximately 18 times stronger than that of thiaramide. It is.

Compound (I) of the present invention is also superior to thiaramide in its antipyretic action. For example, 2-(4-fluorophenyl)-4-(3-chenyl)-5-ethylimidazole or 2-(4-fluorophenyl)-4-(3-
(chenyl)-5-(2-n-propenyl)imidazole is 10-15 times more potent than thiaramide in preventing carrageenin-induced fever. Furthermore, the compound of the present invention (I
) exhibits virtually no ulcerative effect on the digestive system and has extremely low toxicity, making it extremely safe for use as an anti-inflammatory, analgesic and/or antipyretic agent. For example, compound (I) is administered to mice at 1000q.
When administered orally at the dose of //c9, no mouse deaths were observed within 7 days.

A representative example of the chenylimidazole derivative of the present invention is the formula (I
), R1 is a straight-chain or branched alkyl group having 1 to 5 carbon atoms, such as methyl, ethyl, n-propyl, isopropyl or n-butyl, a straight-chain or branched alkenyl group having 2 to 5 carbon atoms, e.g. 2-propenyl or 2
-methyl-2-propenyl, and R2 is halogenophenyl, such as 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 2-chlorophenyl, 3
-chlorophenyl t or 4-'; l chlorophenyl. Among these, preferred are formula (I) in which 1 is methyl, ethyl, n-propyl, isopropyl,
n-butyl, 2-n-propenyl or 2-methyl-2
-n-propenyl, R2 is 2-fluorophenyl, 3
-Fluorophenyl, 4-fluorophenyl, 2-chlorophenyl l: is 4-chlorophenyl. Other preferred compounds are those of formula (I) in which R1 is methyl, ethyl, n-propyl or 2-n-propenyl and 2 is 4-fluorophenyl or 4-chlorophenyl.

Compound (I) of the present invention is produced by reacting a methylamine compound represented by the formula: [In the formula, 1 and 12 are the same as above] with ammonia or a salt thereof.

The ring-closing reaction between the methylamine compound (5) and ammonia or a salt thereof is extremely easily carried out.

For example, the above reaction is preferably carried out in a solvent under heating.

Ammonium salts capable of releasing ammonia in the solvent can be used as starting materials for the above reaction. Representative examples of the ammonium salts include organic acid salts such as ammonium carbonate, ammonium formate, ammonium acetate, ammonium propionate, and ammonium benzoate.

Examples of solvents used include acetic acid, propionic acid, dioxane, toluene, xylene, and chlorobenzene.
-butanol. The above reaction is 100-15
Preferably it is carried out at 0'C, especially from 120 to 140"C. If ammonia is used as the starting material, the reaction should be carried out in a sealed vessel at from 5 to 120 atmospheres.

The chenylimidazole derivative (I) of the present invention has two tautomeric structures as shown in the following formula.

These isomers are also included within the scope of the present invention.

R2R2 (I) (I')C In the formula, 1 and 2 are the same as above. ] The chenylimidazole derivative (I) of the present invention has anti-inflammatory, analgesic and/or
It is also useful as an antipyretic agent. They are also skeletal muscles,
It is used to treat and prevent various types of inflammation in joints (knee joint, shoulder joint, elbow joint, ankle joint, etc.) and other organs. It is also used in the prophylaxis and treatment of rheumatism, gout and arthritis, and inflammation caused by fractures or bone disorders or trauma. They can also be used to prevent pain, fever and other symptoms associated with various types of inflammation.

The chenylimidazole derivative (I) can be used for pharmaceutical purposes as a free base or as a salt thereof. Pharmaceutically acceptable salts of the chenylimidazole derivative (I) include, for example, inorganic acid addition salts such as hydrochloride, phosphate, nitrate and sulfate, organic acid addition salts such as acetate, lactate, citric acid salt, etc. Included are acid salts, tartrates, fumarates, maleates, aspartates, methanesulfonates and benzoates, as well as salts with metals (eg, sodium, potassium, lithium) or amines. These salts are prepared, for example, by neutralizing chenylimidazole derivatives with acids, metal hydroxides or hydrides, or amines.

The chenylimidazole derivative or salt thereof of the present invention can be administered orally or parenterally. Furthermore, this chenylimidazole derivative and its salt can also be used in the form of a pharmaceutical preparation with a pharmaceutical carrier suitable for oral or parenteral administration.

Preferred carriers include, for example, mannitol, lactose, magnesium stearate, starch, talc, cellulose, sucrose, glucose, magnesium carbonate, polypropylene glycol, water, saline, ethanol, glycerin, sodium acetate, and sorbitan monolaure-1.・、
and triethanolamine oleate. The pharmaceutical preparation may be a solid preparation such as a tablet, powder, capsule or granule, or a liquid preparation such as a solution or suspension. Furthermore, for parenteral administration, it may be in the form of an injection.

The compounds used as starting materials for producing the compounds of the present invention are also novel; for example, the compound represented by the formula: is combined with a halide compound represented by the formula: IX [wherein X is a halogen and R1 is the same as above]. In the presence of an acid acceptor (e.g. hydride, potassium tert, -butoxide or alkyl lithium) at -50-30°C in a suitable solvent (
For example, it is prepared by reaction in tetrahydrofuran, dioxane, benzene, toluene, dimethylformamide or dimethyl sulfoxide).

The present invention will now be described in more detail with reference to experimental examples and examples.

Experiment 1 (Anti-inflammatory effect) A suspension of the test compound in a 0.25% carboxymethyl cellulose solution was mixed with Sprague-D a,
wley male rat (weight 160-180g, -
It was administered orally to subjects who had been fasted overnight. 1 hour after administration, 1
% carrageenin saline solution was injected subcutaneously into the sole of either hind paw. The volume of both hind paws was measured 3 hours after the carrageenin injection, and the difference in volume between both hind paws was compared with that of the control group to calculate the protective effect (a) of the test compound against carrageenin-induced edema. The anti-inflammatory effect of the test compound is
30% effective dose (ED3o), ie, the dose that reduces carrageenin-induced edema by 30%. The results are shown in Table 1.

2) Chemical name: 4-C(5-chloro-2-oxo-3-benzothiazolinyl)acetyldi-1-piperazineethanol Experiment 2 (Analgesic effect) A suspension of the test compound in 0.25% carboxymethyl cellulose solution was It was orally administered to male Sprague-Dawley rats (body weight: 60-90 g 1 - overnight fasted). Immediately after administration of the test compound, a 20% dry yeast saline suspension Q, 1 d was subcutaneously injected into the sole of one of the hind paws. Two hours after the yeast injection, a pain meter (Ugo) was used.
(manufactured by Ba5ile) to determine the difference in pain threshold between the inflamed foot and the control foot, and the magnitude of this difference was compared with the control group. 50% effective dose (ED) of test compound
5o), ie, the dose that reduces the pain threshold difference to 50% of the control group, was determined from the dose-effect curve. The results are shown in Table 2.

Table 2 shows 2. Experiment 3 (Antipyretic effect) Sprague-Dawley male rats (body weight 12
0.11 of a 2% saline solution was injected subcutaneously into the sole of one of the hind paws (0 to 1409, - overnight fasted). Three hours after the injection, a suspension of the test compound in 0.25% carboxymethylcellulose was orally administered. Thirty minutes before the injection of carakinin and 2 hours after the administration of the test compound, the rectal temperature of the rat was measured using a thermistor thermometer to examine the antipyretic effect of the test compound. The dose that reduced trial-induced fever by 50% was calculated from the dose-effect curve. The results are shown in Table 3.

2 (Ancer effect) A suspension of a 0.25% carboxymethyl cellulose solution of the test compound was administered to ddY male mice, weight = 18 to 229, -
(Dose: 300M)
flk&). Immediately after administration of the test compound, mice were placed in stress cages and immersed up to the neck in a water bath (24±0.5"C). After 15 minutes, mice were removed and left at room temperature.

Two hours after administration of the test compound, the mice were sacrificed, their stomachs were removed, and
An incision was made along the greater incision and the number of ulcers was examined. As a result, 2
-(4-fluorophenyl)-4-(3-chenyl)=
5-methylimidazole, 2-(4-fluorophenyl)-4-(3-chenyl)-5-methylimidazole and z-(4-fluorophenyl)-4-(3-chenyl)-5-(2 -n-propenyl)imidazole administration group, no ulcers were formed.

Experiment 5 (Acute Toxicity) A suspension of a 0.25% carboxymethyl cellulose solution of the test compound was orally administered to ddY male mice (weight: 18-22 g), and the mice were observed for 7 days to see if they were alive or dead. Compound (I
) was administered at 10,100 O/kQ, no mouse deaths were observed during the observation period.

Example 1 (1) Hydrogenation) IJum (61% dispersion in oil) 0.
94 g were suspended in 25 ffi/dimethylformamide and the suspension was then heated at -40 to -50°C with stirring.
5.26 g of (4-fluorobenzoyl)-(3-thenylcarbonyl)methylamine are added. The mixture was heated to -4
Stir for 5 minutes at 0 to -50"C. Add 3.41F of methyl iodide to this and stir at the same temperature for 1 hour, then stir at 0'C.
Stir at C for 1 hour. Neutralize the reaction mixture with acetic acid,
Add water to this and extract with ethyl acetate. The extract is washed with an aqueous solution of sodium bicarbonate and then with water. The extract is then dried and evaporated under reduced pressure to remove the solvent. The obtained residue was recrystallized from a mixture of ethyl acetate and n-hexane to give N-(4-fluorobenzoyl)-
1-(3-chenylcarbonyl)ethylamine 3.4o
Get y. Yield 65%, melting point 103-105℃IRv'
Di""(cm"): 3370.3100.1
650.1600ax (2) Acetic acid 2wN-(4-fluorobenzoyl)
-1-(3--7-enylcarbonyl)ethylamine 2
．． 771 is added and the mixture is heated at 120-140'C until the ethylamine is dissolved. 20 g of ammonium acetate is gradually added to the mixed solution over 2 hours while stirring. After cooling, 100 d each of water and ethyl acetate are added and neutralized using sodium bicarbonate. The ethyl acetate layer is taken from the mixture, washed with water, and dried. The ethyl acetate is then concentrated under reduced pressure to remove the solvent. The residue was purified by silica gel chromatography (solvent: chloroform) to obtain 2-(
4-fluorophenyl)-4-(3-chenyl)-5-
1.5 g of methylimidazole is obtained. Yield 58%, melting point 171-172°C (recrystallized from a mixture of ethyl acetate and isopropyl ether)
M”): 1610.1590ax Example 2 (1) N-(4-fluorobenzoyl)-(3-chenylcarbonyl)methylamine s, 26f, sodium hydroxide (61% dispersion in oil) 0.91 ', 25 g of dimethylformamide and 3.499 g of ethyl iodide were treated in the same manner as described in Examples 1 to (1) to form N-(4-fluorobenzoyl)-1-(3-thenylcarbonyl).
-4.80 g of n-propylamine are obtained. Yield 82%,
Melting point 105-107"CIRν'di"'" (cII
I”): 3340, 3080, 1675.

max.

1647.1600 (2) 2.91 g of N-(4-fluorobenzoyl L-1-(3-chenylcarbonyl)-n-propylamine,
Example 1 Acetic acid 31I/and ammonium acetate 20f
-(2) to obtain 1.93 g of 2-(4-fluorophenyl)-4-(3-chenyl)-5-ethylimidazole.

Yield 71%, melting point 155-157"C (recrystallized from a mixture of ethanol and diisopropyl ether) IRν'
= “(CIll”): 1618, 1600ma
x.

Example 3 (1) 5.26 y of N-(4-fluorobenzoyl)-3-thenylcarbonyl)methylamine, 0.94 g of sodium hydride (61% dispersion in oil), 25 ml of dimethylformamide and bromide Isopropyl 2.95g
was treated in the same manner as described in Example 1-(1), and
3.33 g of N-(4-fluorobenzoyl)-1-(3-thenylcarbonyl)isobutylamine are obtained. Yield 55%, melting point 114-115° CIRI/""'"(
all”): 3430.3120.1675,1
650°max.

600 (2) N-(4-fluorobenzoyl)-1(3-chenylcarbonyl)isobutylamine 3.05g 1 acetic acid 3
11/ and 20 g of ammonium acetate in Example 1-(2
) to obtain 2.44 g of 2-(4-fluorophenyl)-4-(3-chenylcy-5-isopropylimidazole).

Yield 85%, melting point 184-1.85'C (recrystallized from a mixture of ethyl acetate and diisopropyl ether), I
R & “J”” (ff-1): 1612.1600
max.

Example 4 (1) N-(4-fluorobenzoyl)-(3-thenylcarbonyl)methylamine 5.26 f, sodium Xhydride (61% dispersion in oil) 0.94 F, dimethylformamide 25 t/and n-propyl bromide 2.9! M was treated in the same manner as described in Example 1-(1),
N-(4-fluorobenzoyl)-1-(3-thenylcarbonyl)-n-butylamine 4.01' is obtained. Yield 68%, melting point 92-94"C I Ry 'di3"(3"): 3350,168
0,1640.1600max.

(2) r'1(4-fluorobenzoyl)-1-(3-
chenylcarbonyl)-n-butylamine 3.0591
Acetic acid 3- and ammonium acetate 209 in Example 1-(
2) to obtain 1.40 g of 2-(4-fluorophenyl)-4-(3-+enyl)-5-n-propylimidazole.

Yield 49%, melting point 134-136'C (recrystallized from a mixture of diisopropyl ether and n-hexane), I Rv 'di3''(3''): 1610.159
0max.

Example 5 (1) 5.269 N-(4-fluorobenzoyl)-(5-thenylcarbonyl)methylamine, 0.94 g of sodium Xhydride (61% dispersion in oil), 25 ml of dimethylformamide and bromide 3.29N of n-butyl was treated in the same manner as described in Example 1-(1) to obtain N-(4-
4.259 of fluorobenzoyl)-1-(3-thenylcarbonyl)-0-inchylamine is obtained. Yield 74%
, melting point 101-102°C summer Rν'ji""(crI
I”): 3300.3110.1684.167
5°max.

1633.1605 (2) 3.19 g of N-(4-fluorobenzoyl)-1-(3-chenylcarbonyl)-n-pentylamine,
Example 1 - 3 m of acetic acid and 20 f of ammonium acetate
In the same manner as described in (2), 2.7'l of 2-(4-fluorophenyl)-4-(3-4enyl)-5-n-butylimidazole is obtained.

Yield 93 times, fmJ 144-145°C (recrystallized from a mixture of ethyl acetate and n-hexane) IRν8 di”
”(ffi 1):, 1610.1595max.

Example 6 (1) 5.26 g of N-(4-fluorobenzoyl)-(3-thenylcarbonyl)methylamine, 0.942 g of sodium hydride (61% dispersion in oil), 25% of dimethylformamide and Example 1 - 2.09 g of allyl bromide
Treated in the same manner as described in (1), N-(4-fluorobenzoyl)-1-(chenylcarbonyl)-3-n
-5.27 g of butenylamine are obtained. Yield 87%, melting point 89-92"C.

I Rv 'di'' (cm-1): 3250.
3090.1675, 1630°max.

600 (2) N-(4-fluorobenzoyl)-1-(3-chenylcarbonyl)-3-n-butenylamine 3.03
g, acetic acid 3we and ammonium acetate 20g were treated in the same manner as described in Example 1-(2) to obtain 2-(4-
Fluorophenyl)-4-(3-chenyl)-5-(2
-n-propenyl)imidazole 2.24 g are obtained. Yield 79%, melting point 144-14.5"C (recrystallized from a mixture of ethyl acetate and n-hexane) I Rv 'di3"'(pieces-'): 1640.16
10m1x.

2-(4-fluorophenyl>-4-(3-chenyl)
-5-(2-n-propenyl)imidazole 2.849
is dissolved in 20 ffl/ethyl acetate.

A 10% hydrogen chloride-ethyl acetate solution is added to the solution while cooling with water to make it acidic, and the solution is allowed to stand at room temperature for 5 hours. Separate the crystalline precipitate and wash with ether.

The crystals were recrystallized from methanol to give 2-(4-fluorophenyl L-4-(3-chenyl)-5-(2-n
-propenyl)imidazole hydrochloride 2.82N are obtained.

Yield 88%, melting point 244-247'CIR Si'ji'
"(z"): 3200.3150.3020,1
647°max.

603 Example 7 (1) N-(4-fluorobenzoyl)-(3-thenylcarbonyl)methylamine5. Example 1
- Treated in the same manner as described in (1), N-(4-fluorobenzoyl)-1-(3-chenylcarbonyl)-
4.0 g of 3-methyl-3-n=butenylamine are obtained.

Yield 63%, melting point 114-115°C I Rv 'diE''(z''): 3320.3
090.1680, 1635°max.

1608.1595 (2) 3.17f of N-(4-fluorobenzoyl)-1-(3-thenylcarbonyl)-3-methyl-3-butenylamine, 3ml of acetic acid and 209ml of ammonium acetate.
was treated in the same manner as described in Example 1-(2) to obtain 2-(4
-fluorophenyl)-4-(3-chenyl)-5-(
2-Methyl-2-n-propenyl)imidazole 2.7
Obtain 3g. Yield 91%, melting point 173-174"CIRv'di""(clPI-'): 1676.
1590.1615maX.

Example 8 (1) 5.06 y of N-(4-chlorobenzoyl)-(3-thenylcarbonyl)methylamine, 0.94 f of sodium hydride (61% dispersion in oil), 25 g of dimethylformamide/and iodine Methyl chloride 3,412 was treated in the same manner as described in Example 1-(1) to give N-(4-
Chlorobenzoyl)-1-(3-thenylcarbonyl)
4.81 g of ethylamine are obtained.

Yield 82%, melting point 119-121'C IRν' (cIR): 3300.310
0.16B2, 1640°max.

600 (2) N=(4-chlorobenzoyl)-1-(3-chenylcarbonyl)ethylamine 2.94 g, acetic acid 3 w
, l and 20 g of ammonium acetate in Example 1-(2).
2-(4-chlorophenyl)-4-(3-chenyl)-5-methylimidazole 2.089 is obtained. Yield 76%, melting point 183-184"
C (recrystallized from a mixture of ethyl acetate and diisopropyl ether) IRν"di""(cIR"): 1612.15
95max.

Example 9 (1) 5.60 y of N-(4-chlorobenzoyl)-(3-thenylcarbonyl)methylamine, 0.94 g of sodium hydride (61% dispersion in oil), 25 g of dimethylformamide and iodine 3.49 g of ethyl chloride was treated in the same manner as described in Example 1-(1) to obtain He (4
3.32 g of -chlorobenzoyl)-1-(3-thenylcarbonyl)-n-propylamine are obtained. Yield 54%
, melting point 114-116° CIR 8 3"(z"):
3320.3100.1680,1650゜max
.

Example 1-
Treat in the same manner as described in (2) to obtain 1.85f of 2-(4-chlorophenyl)-4-(3-chenyl)-5-ethylimidazole. Yield 64%, melting point 195-1
96°C (recrystallized from a mixture of ethyl acetate and n-hexane), I Rv 'di3''(cIII''): 3090.
1608.1590max.

Example 10 (1) 5.06 g of N-(4-chlorobenzoyl)-(3-thenylcarbonyl)methylamine, 0.94 f of sodium hydride (61% dispersion in oil)! , 25 wrl of dimethylformamide and 2.95 ml of n-propyl bromide were treated in a manner similar to that described in Example 1-(1),
3.28 g of N-(4-chlorobenzoyl)-1-(3-chenylcarbonyl)-n-butylamine are obtained. Yield 51%, melting point 79-81°C' (31):
3300.3100.1670,1630°IRν max.

595 (2) N-(4-chlorobenzoyl) -1-(3,-
chenylcarbonyl)-n-butylamine 3.22 g,
Example 1 - vinegar wamzg and ammonium acetate 209
Treatment is performed in the same manner as described in (2) to obtain 2-(4-chlorophenyl)-4-(3-chenyl)-5-n-propylimidazole 1.91f.

Yield 63%, melting point 177-179"C (recrystallized from a mixture of ethyl acetate and diisopropyl ether) IRv8
Ji"'"(CM"): 1610.1590ma
x.

Example 11 (1) N-(4-chlorobenzoyl,)-(3-thenylcarbonyl)methylamodi 5.6Of, sodium hydride (61% 7 dispersion in oil) 0.94g, dimethylformamide 25. Isoproyl bromide 2.959 was treated in the same manner as described in Example 1-(1), and
2.40 g of 4-chlorobenzoyl)-1-(3-chenylcarbonyl)isobutylamine are obtained. Yield 37%,
Melting point 122-124'CIRν8di3'''(α-'):
3400.3050.1670,1640°max
.

595 (2) N-(4-chlorobenzoyl)-1-(3-chenylcarbonyl)isobutylamine 3.22 g, acetic acid 3
xi and 20 g of ammonium acetate in Example 1-(2
) to obtain 2.20 g of 2-(4-chlorophenyl)-4-(3,-chenyl)-5-isopropylimidazole. Yield 86%, melting point 194-1
95'C (recrystallized from a mixture of ethyl acetate and diisopropyl ether) IR Si8di'(C'j11')
: 1610.1595max.

Example 12 (1) N-(4-chlorobenzoyl)-(3-thenylcarbonyl)methylamine 5.60f1 Sodium hydride (16% dispersion in oil) 0.94mm, dimethylformamide 25m and allyl bromide is treated in the same manner as described in Example 1-(1) to obtain 5.50 g of N-(4-chlorobenzoyl)-1-(3-thenylcarbonyl)-3-n-butenylamine. Yield 86%, melting point 91-9
3゛C IRν8ji""(m"): 3340.312
0.1660, 1630°max.

595 (2) 3.20 g of N-(4-chlorobenzoyl)-1-(3-chenylcarbonyl)-3-n-butenylamine
, 3III acetate/and 20 g of ammonium acetate were treated in the same manner as described in Example 1-(2) to obtain 2-(4-
Chlorophenyl)-4-(3-chenyl)-5-(2-
n-propenyl)imidazole 1.98II is obtained. Yield: 66%, melting point: 140-142'C (recrystallized from a mixture of ethyl acetate and n-hexane) IR Si'(CM'): 1640.161
0.1595max.

Example 13 (1) 5.26 g of N-(3-fluorobenzoyl)-(3-thenylcarbonyl)methylamine, 0.94 f of sodium hydride (61% dispersion in oil), 25 m of dimethylformamide and bromide. 2.90 g of allyl was treated in the same manner as described in Example 1-(1) to produce N-(3-fluorobenzoyl)-1-(3-chenylcarbonyl).
5.60 units of -3-butenylamine are obtained. Yield 92%,
Melting point 86-88℃ I Rv 'di'''(z'):
3350.3250.3100, 1675°max.

1640.1590 (2) N-(3-fluorobenzoyl)-1-(3-chenylcarbonyl)-3-n-butenylamine 3.03
g, 3 ml of acetic acid and 20 f of ammonium acetate were treated in the same manner as described in Example 1-(2) to obtain 2-(3-fluorophenyl)-4'-(3-chenyl)-5-(
3.56 g of 2-n-propenyl)imidazole are obtained.

Yield 73.7%, melting point 135-136"C IRv5L di3"'((1111-"): 3100
．． 1640.1620,1600°max.

590 Example 14 (1) N-(2-fluorobenzoyl)-(3-thenylcarbonyl)methylamine 5.26F, sodium hydroxide (61% dispersion in oil) 0.94g, dimethylformamide 25M and odor Example 1-
(2-
4.8 g of fluorobenzoyl)-1-(3-chenylcarbonyl)-3-n-butenylamine are obtained. Yield 79
%IRνfi"" (ffi-1): 3410
．． 3090.1680,1650゜max- 625 (2) N-(2-fluorobenzoyl)-1-(3-thenylcarbonyl)-3-n-1 thenylamine 3.03
F, 3d acetic acid and 20g ammonium acetate in Example 1
-2-(2-fluorophenyl)-4-(3-chenyl)-5-(2-
2.96 g of fl-propenyl)imidazole are obtained. Yield 74.4%, melting point 108-109'C I Rv 'di3''' (cIII-1): 3150
．． 30B0,1635,1620゜max 1595.1585 Example 15 (1) To-(3-fluorobenzoyl)-(3-thenylcarbonyl)methylamine 5.26 fl, 1 g of water 61% dispersion in oil of sodium sodium chloride ) 0.94F, dimethylformamide 25d and methyl iodide 3.411I were treated in the same manner as described in Example 1-(1) to obtain N-
4.362 of (3-fluorobenzoyl)-1-(3-thenylcarbonyl)ethylamine is obtained. Yield 78.6
%, melting point 101-103°C 595 (2) N-(3-fluorobenzoyl)-1-(3-chenylcarbonyl)ethylamine 2.77N.

Example 1-(
2-(3-fluorophenyl)-4-(3-chenyl)-5-methylimidazole 2.389 is obtained in the same manner as described in 2). Yield 92%, melting point 193-19
5℃ IRν'di""(cN"): 3100.161
3.1593ax Example 16 (1) N-(2-fluorobenzoyl)=(3-thenylcarbonyl)methylamine 5.26N, sodium X hydride (61% dispersion in oil) 0.94g, dimethylformamide 25ml and 3.41 g of methyl iodide were treated in the same manner as described in Example 1-(1) to obtain N-(2-
4.54 g of fluorobenzoyl)-1-(3-thenylcarbonyl)ethylamine are obtained. Yield 81.8%, melting point 72-73゛CIRv8di3''(z'): 3
420.3100.1680,1653°ax 1620 (2) N-(2-fluorobenzoyl)-1-(3-f
enylcarbonyl)ethylamine 2.779゜acetic acid 3
a, l and 20 g of ammonium acetate in Example 1-(2
) to obtain 3.32 g of 2-(2-fluorophenyl)-4-(3-chenyl)-5-methylimidazole. Yield 85.8%, melting point 121
~122°C I Rv 'di''''(n-'): 3100.3
050.1600,1593ax Patent applicant: Tanabe Seiyaku Co., Ltd. Agent: Patent attorney: Seihaku Hao, and 1 other person

Claims (1)

[Scope of Claims] 2 [In the formula, 1 is a straight-chain or branched alkyl group having 1 to 5 carbon atoms or a straight-chain or branched alkenyl group having 2 to 5 carbon atoms, and R2 is a halogenophenyl group; ] A chenylimidazole derivative or a pharmaceutically acceptable salt thereof. (2) The above-mentioned (X) chenylimidazole derivative-0 (37R' is methyl,
Ethyl, n-propyl, isopropyl, N-butyl, 2
-n-propenyl or 2-methyl-2-n-propenyl, the above (1) or (2) i# enylimidazole derivative. (4) The thhenylimidazole derivative according to item (1), (2) or (3) above, wherein k2 is 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 2-chlorophenyl or 4-chlorophenyl. (5) Formula: [In the formula, R1 means a straight chain or branched alkyl group having 1 to 5 carbon atoms or a straight chain or branched alkenyl group having 2 to 5 carbon atoms, and R2 means a halogenophenyl group] The methylamine compound shown is reacted with ammonia or a salt thereof, and if necessary the product is converted into a pharmaceutically acceptable salt thereof. Process for producing chenylimidazole derivatives and pharmaceutically acceptable salts thereof. 2 [In the formula, R1 means a straight chain or branched alkyl group having 1 to 5 carbon atoms or a straight chain or branched alkenyl group having 2 to 5 carbon atoms, and R2 means a halogenophenyl group] An anti-inflammatory, antipyretic analgesic agent containing an imidazole derivative or a pharmaceutically acceptable salt thereof as an active ingredient. (7) General formula [In the formula, 1 means a straight chain or branched alkyl group having 1 to 5 carbon atoms or a straight chain or branched alkenyl group having 2 to 5 carbon atoms, and R means a halogenophenyl group] A methylamine compound represented by