RU2167150C2 - Polyfluoroalkyl-n-arylcarbamates showing antibacterial activity - Google Patents

Abstract

FIELD: organic chemistry. SUBSTANCE: invention describes novel polyfluoroalkyl-N-arylcarbamates of the general formula: RR′C₆H₃NHCOOCHR″R″′ where R, R' mean H, ortho-, meta- or para-alkyl-C₁-C₃, CF₃, CH₃S, Cl, NO₂, NHCOOCHR''R'''; R'' means H, CF₃; R''' means CF₃, (CF₂)_nH where n = 2-6 or CF₂NO₂ with the exception of 2,2-difluoro-2-nitroethyl-N-phenylcarbamate, 2,2,2-trifluoroethyl-N-p-nitrophenylcarbamate showing the broad spectrum of antibacterial effect at low toxicity that can be used in medicine. EFFECT: new compounds indicated above, valuable properties. 2 tbl

Description

где R и R' = H, о-, м или п-алкил C₁-C₃, CF₃, CH₃S, Cl, NO₂, NHCOOCHR''R''';
R'' = H, CF₃;
R''' = CF₃, (CF₂)_nH, где n = 2-6, или CF₂NO₂ за исключением 2.2-дифтор-2-нитроэтил-N-фенилкарбамата, 2.2.2-трифторэтил-N-п-нитрофенилкарбамата,
обладающие антимикробной активностью.The invention relates to the use of fluorine derivatives of carbamic acid, namely polyfluoroalkyl-N-arylcarbamates of the general formula

where R and R '= H, o-, m or p-alkyl C ₁ -C ₃ , CF ₃ , CH ₃ S, Cl, NO ₂ , NHCOOCHR "R"'';
R "= H, CF ₃ ;
R '''= CF ₃ , (CF ₂ ) _n H, where n = 2-6, or CF ₂ NO ₂ with the exception of 2.2-difluoro-2-nitroethyl-N-phenylcarbamate, 2.2.2-trifluoroethyl-N-p nitrophenyl carbamate,
possessing antimicrobial activity.

The use of bis- (carbamates) from higher (≥ C ₁₀ ) polyfluoroalkanols and toluene diisocyanate used to impart water- and oil-repellent properties to tissues is described [Pat. United States N 3171861, publ. 1965]. The latter compounds go beyond the formula (1) - higher alcohols. Information on the antimicrobial activity of polyfluoroalkyl-N-arylcarbamates is not available in the literature.

 The objective of the invention is to create a fundamentally new substances with high antimicrobial activity of a wide spectrum of action, characterized by extremely low toxicity and completely harmless to humans.

 The essence of the invention is achieved by combining in the proposed compounds an aromatic substituent at the nitrogen atom and ≥ 2 fluorine atoms in the β-position of the alkyl at the residue, which leads to their manifestation of antimicrobial properties. Replacing the N-aryl substituent with benzyl or piperidyl (compounds 25 and 26, Table N 1) sharply reduces their antimicrobial activity. A more remote arrangement of fluorine atoms (compared with the β-position) also reduces bactericidal activity (see compound 27 of table. N 1).

 The methodology for the study of antibacterial activity.

 The antimicrobial activity of the synthesized compounds was studied in a dense nutrient medium by the method of "diffusion in agar" or by the hole method.

The surface of the Petri dish with solid nutrient agar is seeded with a continuous "lawn" suspension of daily culture according to the bacterial standard. The cup is dried for 40 minutes in a thermostat, then 3 drops of a solution of the test substance (10%, 1% or 0.1%) are added to the well in the middle of the cup and the cup is thermostated at 37 ^° C for 24 hours.

 The results of the study are evaluated visually by measuring areas of growth inhibition of microbes after incubation.

 Gram-positive bacteria were used for the tests: white staphylococcus, Staphylococcus aureus golden (906), anthracoid bacillus (1312) and gram-negative Escherichia coli (25922). The results are shown in table. N 1.

 Some of the synthesized compounds were tested on pathogenic fungi — Candida albicaus ATCC 885-653 — unicellular yeast-like fungi, and showed moderate potency.

 As follows from the data table. N 1 claimed polyfluoroalkyl-N-aryl carbamates in their antimicrobial activity are competitive with known bactericides like phenol, monochloramine (DT-1) and even the K-salt of penicillin.

 The results of biological studies are given in table. N 1, indicate that the high antimicrobial activity and low toxicity of the claimed substances makes it possible to use them as chemotherapeutic and antiseptic agents for medical practice, in particular for the prevention of bacterial infections and fungal infections on the surface.

Example. 2.5 g of 1,1,7-trihydrododecafluoroheptanol-1 and 3 drops of triethylamine were added to 0.9 g of phenylisocyanate; after the end of the exothermic reaction, the mixture was heated for 1 h in a boiling water bath and crystallized from hexane. Yield 2.6 g (76.5%) of 1,1,7-trihydrododecafluoroheptanyl-N-phenylcarbamate, mp. 47-48 ^o C. Similarly, other compounds are presented, are presented in table. N 2.

 The properties of the obtained compounds and their yield are given in table. N 2.

Claims (1)

Polyfluoroalkyl-N-arylcarbamates of Formula I

where R, R '= H, o-, m-, or p-alkyl C ₁ -C ₃ , CF ₃ , CH ₃ S, Cl, NO, NHCOOCHR "R"'';
R "= H, CF;
R '''= CF ₃ , (CF ₂ ) _n H, where n = 2-6, or CF ₂ NO ₂ , with the exception of 2,2-difluoro-2-nitroethyl-N-phenylcarbamate, 2,2,2- trifluoroethyl-Nn-nitrophenylcarbamate,
possessing antimicrobial activity.

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