Polyimino ketoaldehydes

Abstract

The compounds with the general formula I are disclosed ##STR00001##
where n.sub.1 is the number of carbon atoms connected to nitrogen atom by a double bond and can take on values of 25 to 41, and where n.sub.2 is the number of —CH.sub.2— groups and can take on values of 15 to 23, as well as their biologically acceptable salts and solvates.

Claims

1. A compound with the general formula ##STR00005## where n.sub.1 is the number of carbon atoms connected to nitrogen atom by a double bond and can take values of 25 to 41, and where n.sub.2 is the number of —CH.sub.2— groups and can take values of 15 to 23, or a biologically acceptable salt or solvate thereof.

2. The compound according to claim 1, wherein n.sub.1 is 25, 33, or 41, and n.sub.2 is 15, 19, or 23.

3. The compound according to claim 2, wherein said compound is a 1-amino-tetratriacontyl-henicosa-20-on-21-al.

4. The compound according to claim 1, wherein said compound is a 1-amino-tetratriacontyl-henicosa-20-on-21-al.

5. A pharmaceutical preparation comprising a biologically effective concentration of a compound with the general formula ##STR00006## where n.sub.1 is the number of carbon atoms connected to nitrogen atom by a double bond and can take values of 25 to 41, and where n.sub.2 is the number of —CH.sub.2— groups and can take values of 15 to 23, or a pharmaceutically acceptable salt or solvate thereof.

6. A pharmaceutical preparation according to claim 5 wherein n.sub.1 is 25, 33, or 41, and n.sub.2 is 15, 19, or 23.

7. The pharmaceutical preparation according to claim 5, wherein said preparation comprises a biologically effective concentration of the compound 1-amino-tetratriacontyl-henicosa-20-on-21-al or a pharmaceutically acceptable salt or solvate thereof.

8. The pharmaceutical preparation according to claim 7, further comprising at least one pharmaceutically acceptable excipient.

9. The pharmaceutical preparation according to claim 5, further comprising at least one pharmaceutically acceptable excipient.

10. A compound with the general formula ##STR00007## where n.sub.1 is the number of carbon atoms connected to nitrogen atom by a double bond and can take values of 25 to 41, and where n.sub.2 is the number of —CH.sub.2— groups and can take values of 15 to 23, as a drug.

11. A compound according to claim 10 wherein n.sub.1 is 25, 33, or 41, and n.sub.2 is 15, 19, or 23.

12. A compound according to claim 10, wherein said compound is a 1-amino-tetratriacontyl-henicosa-20-on-21-al.

13. A compound according to claim 12 for treatment of anthrax, bacterial meningitis, brucellosis, bubonic plague, diphtheria, epidemic typhus, gonorrhoea, whooping cough (pertussis), campylobacteriosis, chlamydia, cholera, plague, legionellosis, leprosy (Hansen's disease), leptospirosis, listeriosis, Lyme disease, melioidosis, nocardiosis, pneumonia, relapsing fever, psittacosis, q fever, salmonella, syphilis, MRSA infection, scarlet fever, shigellosis, tetanus, typhus, typhoid fever, tuberculosis, tularemia, or rat-bite fever.

14. A compound according to claim 10, for treating a bacterial infection caused by gram-positive or gram-negative bacteria.

15. A compound according to claim 14 for treatment of anthrax, bacterial meningitis, brucellosis, bubonic plague, diphtheria, epidemic typhus, gonorrhoea, whooping cough (pertussis), campylobacteriosis, chlamydia, cholera, plague, legionellosis, leprosy (Hansen's disease), leptospirosis, listeriosis, Lyme disease, melioidosis, nocardiosis, pneumonia, relapsing fever, psittacosis, q fever, salmonella, syphilis, MRSA infection, scarlet fever, shigellosis, tetanus, typhus, typhoid fever, tuberculosis, tularemia, or rat-bite fever.

16. A method of treating a bacterial infection caused by gram-positive or gram negative bacteria comprising the step of administering an effective amount of a compound with the general formula ##STR00008## where n.sub.1 is the number of carbon atoms connected to nitrogen atom by a double bond and can take values of 25 to 41, and where n.sub.2 is the number of —CH.sub.2— groups and can take values of 15 to 23.

17. The method according to claim 16 wherein n.sub.1 is 25, 33, or 41, and n.sub.2 is 15, 19, or 23.

18. The method according to claim 16 wherein said compound is a 1-amino-tetratriacontyl-henicosa-20-on-21-al.

19. The method according to claim 16 wherein said bacterial infection is anthrax, bacterial meningitis, brucellosis, bubonic plague, diphtheria, epidemic typhus, gonorrhoea, whooping cough (pertussis), campylobacteriosis, chlamydia, cholera, plague, legionellosis, leprosy (Hansen's disease), leptospirosis, listeriosis, Lyme disease, melioidosis, nocardiosis, pneumonia, relapsing fever, psittacosis, q fever, salmonella, syphilis, MRSA infection, scarlet fever, shigellosis, tetanus, typhus, typhoid fever, tuberculosis, tularemia, or rat-bite fever.

Description

EXAMPLE 1—PREPARATION of 1-AMINO-TETRATRIACONTYL-HENICOSA-20-ON-21-AL

(1) 0.1 mol/L of acetate buffer is prepared by mixing 0.1 mol/L aqueous octenic acid solution with 0.1 mol/l aqueous NaOH solution. The resulting solution has a pH of 6.

(2) NRPS1 suspension was prepared in acetate buffer. Final NRPS1 concentration in suspension amounted to 0.06 g/L.

(3) 0.51 g of glycine, 0.85 g of MgCl.sub.2, 0.043 g of ATP was added to the reaction flask with magnetic stirrer and the mixture was dissolved in 85 mL of previously prepared acetate buffer. Reaction is initiated by adding 85 μL of NRPS1 suspension to the reaction flask. The temperature at which the reaction occurred was 27° C. The stirring rate of the magnetic stirrer amounted to 500 spins/min, and the reaction time was 120 min. The reaction was stopped by admixing 85 mL 7% v/v water solution of trichloroacetic acid (ratio of reaction mixture and acid is 1:1). The reaction vessel was then placed on ice for 30 minutes. After cooling, the process of evaporation on a rotating evaporator with water bath was initiated. After removal of water, additional drying on rotary evaporator with water bath with a temperature of 60° C. for more than one hour was conducted. 0.46 g of white precipitate—with temperature of 125° C. was obtained. The sample was dissolved in isopropanol and analysed with high-resolution mass spectrometry (ESI-qTOF) on Synapt G2-Si (Waters, USA). Mass spectres were recorded in positive and negative ion mode operation. The calculated peak was supposed to appear at 445.50 m/z, and the observed peak was at 445.6564 inferring that the characteristic peak for compound 1-amino-tetratriacontyl-henicosa-20-on-21-al is at 445.7959 with mass measurement error within the accuracy limits at 5 ppm—see picture 1.

EXAMPLE 2—COMPOSITION OF ORAL PREPARATION

(4) 500 mg of 1-Amino-Tetratriacontyl-Henicosa-20-on-21-al 500 mg of Excipients

(5) Excipients in this example are hypromellose, microcrystalline cellulose, dye, titanium dioxide.

(6) The following invention aspect concerns antibacterial activity of the compound with general formula I

(7) ##STR00004##

(8) in particular antibacterial activity of 1-amino-tetratriacontyl-henicosa-20-on-21-al. In vitro testing showed that the compound with general formula I, as well as compound 1-1-amino-tetratriacontyl-henicosa-20-on-21-al, shows antibacterial properties against gram-positive and gram-negative bacteria including multi-resistant bacteria.

(9) The compound with general formula I demonstrates antibacterial properties against the following bacteria: Neisseria gonorrhoea, Acinetobacter baumannii, Staphylococcus aureus (MRSA, Burkholderia cepaci, Pseudomonas aeruginos, Clostridium difficil, Escherichia coli (E. coli ESBL, Mycobacterium tuberculosis, Klebsiella pneumoniae, Streptococcus pyogenes. Table 1 shows inhibition zones for Avian Pathogenic Escherichia coli multi-resistant strain against 1-amino-tetratriacontyl-henicosa-20-on-21-al, Amoxicillin, Trimethoprim sulphate, tetracycline and Sulfadimidine.

(10) As shown, only 1-amino-tetratriacontyl-henicosa-20-on-21-al has an effect on the inhibition of the stated strain of E. Coli.

(11) Table 1 contains the results for inhibition diameter expressed in mm. Table 2 shows minimal concentration of 1-amino-tetratriacontyl-henicosa-20-on-21-al expressed in mg/mL that is necessary for the inhibition of Avian Pathogenic Escherichia coli multi-resistant strain. 1-amino-tetratriacontyl-henicosa-20-on-21-al is marked in tables as Cm. Antibiotics from Table 1 are administered in their standard dose for this type of testing. It is evident that only 1-amino-tetratriacontyl-henicosa-20-on-21-al shows inhibitory activity against Avian Pathogenic Escherichia coli multi-resistant strain.

(12) TABLE-US-00002 TABLE 1 Inhibition zones of Avian Pathogenic Escherichia coli multi-resistant strain in mm Concentration Inhibition zone 20 μL of CM compound solution (350 μg/1 μL) per disc 10 mm  15 μL of CM compound solution (350 μg/1 μL) per disc 9 mm 10 μL of CM compound solution (350 μg/1 μL) per disc 8 mm Amoxicillin (25 μg per disc) 0 mm Trimethoprim sulphate (1.25 μg + 23.75 μg per disc) 0 mm Tetracycline (30 μg per disc) 0 mm Sulfadimidine (300 μg per disc) 0 mm

(13) TABLE-US-00003 TABLE 2 Minimum inhibitory concentration of 1-amino-tetratriacontyl- henicosa-20-on-21-al necessary for inhibition of Avian Pathogenic Escherichia coli multi-resistant strain Concentration Inhibition 80 mg/1 ml + 8 mg/1 ml + 0.8 mg/1 ml + 0.08 mg/1 ml −

(14) Given the results of in-vitro testing, the compounds with general formula I, especially 1-amino-tetratriacontyl-henicosa-20-on-21-al, represent medications, mainly medications against bacterial infections and are used in the treatment of bacterial infections. The bacterial infections that compounds with general formula I, especially 1-amino-tetratriacontyl-henicosa-20-on-21-al, successfully treat are: anthrax, bacterial meningitis, brucellosis, bubonic plague, diphtheria, epidemic typhus, gonorrhoea, whooping cough (pertussis), campylobacteriosis, chlamydia (trachoma), cholera, plague, legionellosis, leprosy (Hansen's disease), leptospirosis in humans, leptospirosis, listeriosis, Lyme disease, melioidosis, nocardiosis, pneumonia, relapsing fever, psittacosis, q fever, salmonella, syphilis, MRSA infection, scarlet fever, shigellosis, tetanus, typhus, typhoid fever, tuberculosis, tularemia, rat-bite fever.