JPH0242065A - 2-acylimidazole derivative - Google Patents

Abstract

NEW MATERIAL:The 2-acylimidazole derivative of formula I [R<1> is lower alkyl; R<2> is furyl, pyridyl, styryl or substituted phenyl (the substituent is lower alkoxy, carboxy, nitro, di(lower alkyl)amino or halogen)]. EXAMPLE:The compound of formula I wherein R<1> is CH3 and R<2> is group of formula II. USE:Antimycotic agent and antifungal agent. PREPARATION:The compound of formula I can be produced e.g., by reacting an imidazole derivative of formula III with n-butyllithium and with dimethylacetamide and reacting the resultant 2-acetylimidazole derivative of formula IV with an aldehyde compound of formula V.

Description

DETAILED DESCRIPTION OF THE INVENTION (Field of Industrial Application) The present invention relates to novel 2-7 syl imigsolyl derivatives and salts thereof, which have antifungal and antifungal effects and are used as antifungal agents and antifungal agents. Qiq1 is m.

(Prior Art) Many imiguzole derivatives have been found as pharmaceuticals and agricultural chemicals, but there are very few reports on 2-position acyl derivatives. As a 2-position acyl derivative similar to the compound of the present invention, a report by the present inventors is given in Heterocycles, Vol. 23.

1759g (1985) (Heterocycle
s* 23. 1759 (1985)) and Chemical 7 Arman Ute Carbyuretin Volume 34, 4
196 pages (1986) (Chem.

Pharm, Bull, 34. 4196 (19
8B)), but the pharmacological effects of these compounds are not described.

(Problems to be Solved by the Invention) An object of the present invention is to provide a novel 2-7 syl imigsolyl derivative having excellent antifungal and antifungal effects.

(Means for Solving the rX Problem) The present invention is based on the general formula , a carboxyl group, a nitro group, a lower alkylamine group, or a halogen atom), and salts thereof.

In the definition of the compounds of the present invention, the lower alkyl group refers to an alkyl group having 1 to 4 carbon atoms such as methyl, ethyl, propyl, isopropyl, butyl, 5ea-butyl, etc., and the lower alkoxy group refers to methoxy, ethoxy, propyloxy, Examples of the alkoxy groups having 1 to 4 carbon atoms such as butoxy and terj-butoxy groups and halogen atoms include fluorine, chlorine, bromine, and iodine.

Salts included in the present invention are not particularly limited as long as they are pharmaceutically acceptable, but general examples include mineral acid salts such as hydrochloric acid, sulfuric acid, and nitric acid, and organic acid salts such as oxalic acid, maleic acid, and malic acid. .

The 2-7 syl imigsol derivatives of the present invention are, for example, as follows:
It can be produced according to the method shown in the reaction formula.

<Reaction formula> (■) A process (1) B process (
In the formula, R1 and R2 are the same as above.) Each step in the above reaction formula is carried out in more detail as follows.

<Step A> The imiguzole derivative represented by the general formula (II) is reacted with ■-butyllithium in a suitable solvent, and then dimethylacetamide is reacted with the imiguzole derivative represented by the general formula (I).
A 2-7 cetyl imigsol derivative represented by II) is obtained. The solvent is not particularly limited as long as it does not participate in this reaction, but examples include noethyl ether, diisopropyl ether, and tetrahydro-7-lane (T HF ).
, ethers such as nooxane are preferably used. The ratio of the imiguzole derivative (II) to n-butyllithium and dimethylacetamide to be used can be selected as appropriate, but it is usually preferably about 1.0 to 1.2 times the molar amount of the compound (II). The reaction is usually carried out under cooling at about -10 to -100°C, and generally proceeds advantageously at -50 to -80°C.

Step B> A 2-7 cetyl imigzoyl derivative represented by the general formula (I [ Compound (1) of the present invention is produced by subjecting it to Kunevenadel condensation reaction.

These condensation reactions are famous reactions, for example, O in the Merck Index 10th Ed.
itiono rganic name reac
tions).

Catalysts currently used include alkali metal or alkaline earth metal catalysts such as potassium hydroxide, sodium hydroxide, calcium hydroxide, sodium carbonate, sodium bicarbonate, sodium methoxide, sodium nidoxide, and sodium acetate. Hydroxides, carbonates, alkoxides, and more! acid salts, methylamine, ethylamine, diethylamine, triethylamine, aniline, nicotine,
Amines such as pyrinone, piperidine, and ammonia and organic acid anhydrides such as acetic anhydride and propionic anhydride are used. The ratio of compound (I[[) and aldehyde compound (IV) to be used can be selected as appropriate, but in general, it is preferable to use about 1.0 to 1.2 times the mole of compound (III) to the aldehyde compound (■). . The reaction is usually carried out under heating, and generally proceeds advantageously at the reflux temperature of the solvent. As the solvent, alcohols such as methanol and ethanol, ethers such as nooxane, and acetic acid are used.

The novel 2-acylimiguzole derivative of the present invention produced by the above reaction can be easily isolated by conventional separation means such as recrystallization, column chromatography, etc.

(Example) Next, reference examples and examples will be given to explain the present invention more specifically.
I will clarify.

Reference Example 1 Under a nitrogen stream, 3.28 g of 1-methyl imiguzole was dissolved in anhydrous THF and cooled to -80°C. This a, a”
-7 After adding 10 mH of pyrifle, 1.55 M of 11-butyl! A hexane solution of Notium 661 was added dropwise.

After stirring at the same temperature for 10 minutes, 3.4 g of N,N-tmethylacetamide was added. Then stir for 30 minutes at room temperature,
After the reaction, add 10% hydrochloric acid 25+al and ether 8 to the reaction solution.
0 duck 1 was added and the liquid was separated. The hydrochloric acid layer was made alkaline with potassium carbonate and extracted with 50 ml of ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, and after drying, the solvent was distilled off and the resulting residue was purified by vacuum distillation to obtain 1-methyl-2-7.
4.7 g (95%) of cetyl imiguzole was obtained.

Boiling, 4 to O ~ 110°C/3 mmHg (colorless oil) H-NMR (CDC1,) δ: 2,66 (s
, 3H.

CHrCO), 4.00(s, 3H-NC1
4*)-7,03,7,14(d, 2H) Example 1 0.62 g of 1-methyl-2-7 cetyl imiguzole and 0.67 g of cinnamaldehyde were dissolved in 25 parts of methanol, and dissolved in this. 0.2 g of sodium hydroxide was added, and the mixture was stirred at room temperature for 4 hours. After the reaction, the solvent was distilled off, and ethyl acetate 501 was added to the residue for extraction. After washing with water, the organic layer was dried over anhydrous sodium sulfate. After drying, the solvent was distilled off and the resulting residue was recrystallized from n-hexane to convert compound 1a to O,
h (76%) was obtained.

Examples 2 to 11 Compounds I) to I shown in Table 1 in the same manner as Example 1
synthesized k.

hand Continued Supplementary Positive book 1986 Patent Application No. 192314 2. Name of the invention 2-7 syl imigsol derivative 3゜ 4゜ person who makes corrections Relationship to the incident Patent applicant Taiho Pharmaceutical Co., Ltd.

Claims (1)

[Claims] (1) General formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (In the formula, R^1 is a lower alkyl group, R^2 is a furyl group,
A pyridyl group, a styryl group, or a substituted phenyl group, and the substituent is a lower alkoxy group, a carboxyl group, a nitro group,
2-acylimidazole derivatives represented by (di-lower alkylamino group or halogen atom) and salts thereof.