RU2008116170A - DERIVATIVES OF TRIINDOLYLMETHANES SUBSTITUTED IN THE INDO KERNEL, METHOD FOR PRODUCING THEM AND THEIR ANTIBACTERIAL AND ANTI-FUNGAL ACTIVITY - Google Patents

Abstract

1. Compounds corresponding to the formula I or II! ! ! where R1; R7; R13 is independently hydrogen, alkyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, provided that at least one of the substituents R1; R7; R13 is different from H; ! R2; R8; R14 are independently hydrogen, alkyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl; halogen, -OH, -OR,! = O; -COOH, -COOR; -NH2, -N (R) 2; -N + (R) 3, -CN, -SO2R, -SOR, -CRO, acyl, carbamoyl, thiocarbamoyl, R, where R may be the same or different substituents selected from the series hydrogen, alkyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl , and any of the substituents can in turn be substituted, while the number of substituents is from 1 to 3, and the position of any substituents can vary; ! R3-R6; R9-R12; R15-R18 are independently hydrogen, alkyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl; halogen, -OH, -OR, -COOH, -COOR; -NO2, -NO, -NH2, -NHRa; -N (R) 2; -N + R3, -CN ,, -SO2R, -SO2N (R) 2; -SOR, -CRO, -O-Sug,! -N-Sug, acyl, carbamoyl, thiocarbamoyl, R, where R may have the same or different values, selected from the series hydrogen, alkyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, Sug is any cyclic or acyclic carbohydrate, and any of the substituents may in turn be substituted, the number of any substituents may vary from 1 to 3,! Y- represents the anion of any pharmacologically acceptable organic or inorganic acid; ! R19 represents hydrogen, alkyl, acyl, metal ion,! in the form of any stereoisomers, enantiomers or diastereomers, racemates, which can be enriched in one of the forms, if possible, as well as their solvates, pharmaceutically acceptable salts

Claims (17)

1. Compounds corresponding to formula I or II

where R ₁ ; R ₇ ; R ₁₃ independently represent hydrogen, alkyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, provided that at least one of the substituents R ₁ ; R ₇ ; R ₁₃ is different from H; R ₂ ; R ₈ ; R ₁₄ independently represent hydrogen, alkyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl; halogen, -OH, -OR, = O; -COOH, -COOR; -NH ₂ , -N (R) ₂ ; —N ⁺ (R) ₃ , —CN, —SO ₂ R, —SOR, —CRO, acyl, carbamoyl, thiocarbamoyl, R, where R may be the same or different substituents selected from the range hydrogen, alkyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, and any of the substituents may in turn be substituted, wherein the number of substituents is from 1 to 3, and the position of any substituents may vary; R ₃ -R ₆ ; R ₉ -R ₁₂ ; R ₁₅ -R ₁₈ independently represent hydrogen, alkyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl; halogen, -OH, -OR, -COOH, -COOR; -NO ₂ , -NO, -NH ₂ , -NHR _a ; -N (R) ₂ ; -N ⁺ R ₃ , -CN ,, -SO ₂ R, -SO ₂ N (R) ₂ ; -SOR, -CRO, -O-Sug, -N-Sug, acyl, carbamoyl, thiocarbamoyl, R, where R may have the same or different values, selected from the series hydrogen, alkyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, Sug is any cyclic or acyclic carbohydrate, and any of the substituents may in turn be substituted, the number of any substituents may vary from 1 to 3, Y ^- represents the anion of any pharmacologically acceptable organic or inorganic acid; R ₁₉ represents hydrogen, alkyl, acyl, metal ion, in the form of any stereoisomers, enantiomers or diastereomers, racemates, which can be enriched in one of the forms, if possible, as well as their solvates, pharmaceutically acceptable salts in amorphous or crystalline form. 2. A pharmaceutical composition having an antibacterial or antifungal effect, comprising a therapeutically effective amount of at least one compound of Formula I or II in a mixture with at least one acceptable carrier. 3. The method of obtaining compounds corresponding to formula I, which consists in the fact that the method is carried out according to scheme I

including the following steps: dissolving or dispersing the starting triindolylmethane in an organic or inorganic solvent with the addition of the acid corresponding to the resulting salt, or dissolving or dispersing the starting triindolylmethane directly in the acid corresponding to the obtained salt, and oxidation by contacting the resulting solution or dispersion with oxygen or an oxygen-containing gas mixture or solutions containing dissolved oxygen, isolation of the obtained product in the form of the corresponding salt of triindolylmethyl. 4. The method according to claim 3, characterized in that the process is conducted in the presence of substances that increase the contact surface of the liquid and gaseous phases, such as, for example, activated carbon, or substances and conditions that increase the solubility of oxygen in these environments. 5. A method of producing compounds corresponding to formula II from compounds corresponding to formula I, by treating the latter in a dissolved, or solid, or in a molten state with solutions having a pH> 7, or by fusion or exposure to them with solid salts of alkali or alkaline earth metals, or the action on them of basic salts or carbonates of metals or amines according to Scheme II

6. A method of obtaining compounds of formula I from compounds of formula II by treating the latter in a dissolved, or solid, or in a molten state with solutions having a pH <7, or by applying liquid, solid, or gaseous acids to them according to Scheme III

7. A method of obtaining compounds corresponding to formula III

(in which the values of R ₁ -R ₁₈ correspond to those for formula I), which means that indoles unsubstituted at the 3-C atom with more electron-donating substituents in the nucleus (substituents that increase the electron density at the 3-C atom of the indole ring) replace the indoles with less electron-donating substituents in triindolylmethanes under the action of weakly acidic catalysts and / or Lewis acids when components are mixed according to the following scheme IV:

where R, R _{1 in} total or separately create an electron density on the 3-C atom of the indole ring that is less than R ₂ and R _{3 in} total or separately. 8. The method according to claim 7, characterized in that the process is carried out by heating in a suitable solvent or melt. 9. The method according to any one of claims 7 and 8, characterized in that the process is carried out by boiling in alcohols and using lanthanides as triflates as catalysts. 10. A method of inhibiting the activity of gram-positive and gram-negative microorganisms by the administration of a pharmaceutically effective amount of a compound corresponding to formula I or II, or a pharmaceutical composition containing a therapeutically effective amount of at least one compound corresponding to formula I or II in a mixture with at least one acceptable carrier or solvent. 11. A method of inhibiting the propagation of pathogenic bacterial microflora on environmental objects or materials susceptible to the destructive effects of bacterial microflora, comprising treating these objects, for example, for antiseptic or disinfection purposes, or materials, for example, for preservation, with an effective amount of a compound corresponding to formula I or II, or a composition containing an effective amount of at least one compound corresponding to formula I or II, in a mixture with at least one acceptable carrier or solvent 12. A method of inhibiting fungal activity, comprising administering a pharmaceutically effective amount of a compound according to formula I or II, or a pharmaceutical composition containing a therapeutically effective amount of at least one compound corresponding to formula I or II, in a mixture with at least one acceptable carrier or solvent. 13. A method of inhibiting the activity of pathogenic fungal microflora on objects of the environment or materials susceptible to the destructive effects of fungal microflora, comprising treating these objects, for example, for the purpose of antiseptics and disinfection, or materials, for example, for the purpose of preservation, with an effective amount of the compound corresponding to formula I or II, or a composition containing an effective amount of at least one compound corresponding to formula I or II, in a mixture with at least one acceptable carrier or solvent 14. A method of using the compounds of formula I or II as antibacterial agents (against gram-positive and gram-negative bacteria), comprising administering to one of the known methods (for example, topically, orally, intravenously, intramuscularly, etc.) to a person or animal suffering from bacterial infection, a pharmaceutically effective amount of a compound corresponding to formula I or II, or a pharmaceutical composition containing a therapeutically effective amount of at least one compound, with Resp formula I or II, in admixture with at least one acceptable carrier or diluent. 15. A method of using compounds corresponding to formula I or II as agents that prevent the propagation of pathogenic bacterial microflora on environmental objects (for example, for antiseptic and disinfection purposes) or materials susceptible to the destructive effects of bacterial microflora (for example, as a preservative), including treating these objects or materials with an effective amount of a compound according to Formula I or II, or a composition containing an effective amount of at least one compound, The appropriate formula I or II, in admixture with at least one acceptable carrier or diluent 16. A method of using the compounds of formula I or II as antifungal agents, comprising administering, using one of the known methods (for example, topically, orally, intravenously, intramuscularly, etc.) to a person or animal suffering from a fungal infection, a pharmaceutically effective amount of a compound corresponding to the formula I or II, or a pharmaceutical composition containing a therapeutically effective amount of at least one compound corresponding to formula I or II, in a mixture with at least one media or solvent. 17. The method of application of the compounds corresponding to formula I or II as agents that prevent the propagation of pathogenic fungal microflora on environmental objects (for example, for antiseptic and disinfection purposes) or materials susceptible to the destructive effects of fungal microflora (for example, as a preservative), including treating these objects or materials with an effective amount of a compound according to Formula I or II, or a composition containing an effective amount of at least one compound, respectively vuyuschego formula I or II, in admixture with at least one acceptable carrier or diluent