COMPOUNDS AND COMPOSITIONS

Abstract

Compounds are revealed that have the formula (1), where R is an alkane chain having between 8 and 20 carbon atoms, and A is one or more anions having a total charge of -2; or R is a quaternary amine having the formula (2), where R a and R b They are, each, an alkane chain that has between 8 and 20 carbon atoms, and A is one or more anions that has a total charge of -3.

Description

COMPOUNDS AND COMPOSITIONS. The present invention relates to compounds that can be used to treat Herpesviridae, Human Papillomavirus, bacterial infections, and fungal infections. Background. The Herpesviridae family is a large group of DNA viruses responsible for a number of diseases in both humans and animals. The most common Herpesviridae that cause disease in humans are the varicella-zoster virus (chickenpox virus), the Epstein-Barr virus, cytomegalovirus, herpes simplex virus 1, and herpes simplex virus 2. The varicella-zoster virus is a common virus that causes chickenpox in children and shingles (herpes zoster) in adults. The Epstein-Barr virus is the virus that commonly causes infectious mononucleosis (glandular fever), and is also associated with types of cancer such as Hodgkin lymphoma, Burkitt lymphoma, and gastric cancer. Cytomegalovirus is another member of the Herpesviridae family of viruses. Human cytomegalovirus (HCMV, or CMV, or human herpesvirus-5 (HHV-5)) is a virus associated with the salivary glands and is usually undetectable by healthy individuals, but it can be life-threatening for immunocompromised individuals, such as patients with HIV, organ transplant recipients, and newborns. 1 Herpes simplex virus 1 and herpes simplex virus 2 are the two viruses responsible for the viral disease herpes simplex. Both viruses can cause oral and genital infections, although HSV-1 is more commonly associated with oral infections (e.g., oral herpes), while HSV-2 is more commonly associated with genital infections (e.g., genital herpes). Herpes simplex viruses cause infections that affect approximately 60% to 95% of adults worldwide (Chayavichitsilp P, Buckwalter JV, Krakowski AC, Friedlander SF (April 2009). "Herpes simplex". Pediatr Rev. 30 (4)). Oral herpes is commonly associated with the face and / or mouth and can cause small blisters that form herpes labialis (cold sores). Oral herpes can also include other symptoms such as sore throat, fever, muscle aches, swollen lymph nodes, headache, and malaise, particularly during the first outbreak after infection. Genital herpes is typically associated with the genitals and can cause small lesions in the genital area, inner thighs, buttocks, and / or rectum. Other typical symptoms associated with this virus include pain, itching, irritation, discharge, fever, headache, muscle pain, swollen lymph nodes, and malaise. Oral herpes can be treated with antiviral medications. which can reduce the duration of symptoms, but do not kill 2 completely to the responsible virus. After resolving the symptoms of a herpes infection, the herpes virus (e.g. HSV-1 or HSV-2) generally remains dormant in the branches of the facial nerve, and the virus can reactivate periodically to cause cold sores in the same area of ​​the mouth or face as the site of the original infection. In some In humans, the virus remains asymptomatic, although transmission is possible even when symptoms are not present. present. Genital herpes can also be treated with antiviral medications, which can reduce the duration of symptoms. However, for oral herpes, there is no approved medication that completely eradicates the virus responsible from the human body. Human papillomavirus (HPV) is responsible for HPV infection, which generally does not cause any symptoms and resolves spontaneously. However, in some cases, infections persist and cause warts or precancerous lesions. Precancerous lesions can increase the risk of several types of cancer, including cervical, vaginal, penile, rectal, oral, and throat cancers (Ljubojevic, Suzana; Skerlev, Mihael (2014). "HPV-associated diseases"). [HPV-associated diseases]. Clinics in Dermatology. 32 (2): 227-234.). HPV is the most common human-transmitted infection sexually transmitted globally and most people get infected in 3 at some point during their lives (Milner, Danny A. (2015). Diagnostic Pathology: Infectious Diseases. Elsevier Health Sciences. p. 40). Bacterial and fungal infections are common worldwide. Several medications have been developed to treat these infections, and these can target specific or broad types of bacterial and fungal species and strains. Antibiotic resistance, and more recently antifungal resistance, is becoming increasingly prevalent and is undoubtedly a growing problem worldwide. With this in mind, there is a global need for new medications capable of treating bacterial and fungal infections. Considering the prevalence of the Herpes virus (particularly the Herpes Simplex virus) and the Human Papillomavirus, as well as the scale of diseases associated with these viruses, there is a need for a treatment that focuses on these viruses and can treat the diseases associated with them. In a first aspect of the present invention, a compound that has the following formula: (Formula I) where R is an alkane chain having between 8 and 20 carbon atoms and A is one or more anions having a total charge of -2; or R is a quaternary amine having the following formula: Where Ra and Rb are each an alkane chain having between 8 and 20 carbon atoms, and A is one or more anions having a total charge of -3. R can be, for example, a linear or branched saturated alkane chain having between 8 and 18 carbon atoms, for example 8 and 16 carbon atoms, for example 8 and 14 carbon atoms, for example 9 and 15 carbon atoms, for example 10 carbon atoms. Preferably, R is a linear saturated alkane chain having between 8 and 16 carbon atoms, for example 10 carbon atoms. R can be, for example, a quaternary amine according to formula (Ia), in which Ra and Rb are each a linear or branched saturated alkane chain having between 8 and 18 carbon atoms, for example 8 and 16 carbon atoms, for example 8 and 14 carbon atoms, for example 9 and 15 carbon atoms, for example 10 carbon atoms. Ra and Rb can each be a linear or branched saturated alkane chain having a different number of carbon atoms. Preferably, Ra and Rb are each a linear saturated alkane chain having between 8 and 16 carbon atoms, for example 10 carbon atoms. A saturated linear alkane chain can be represented by the following formula: where n is the number of repeating units that is the number of carbon atoms in the alkane chain linear. As^ in the case where R is an alkane chain that has between 8 and 20 carbon atoms, it is preferable that R be where n is between 8 and 16 For example, 10. In the case where R is a quaternary amine having the formula (Ia) As stated above, it is preferred that Ra and Rb be where n is between 8 and 16, for example 10. A may include, for example, halide ions, such as chloride ions (Cl-), bromide ions (Br-), iodide ions (I-), and / or fluoride ions (F-). A may also include, for example, ions of other organic and inorganic acids, such as sulfate (SO42-), carbonate (CO32 ), hydrogen carbonate (HCO3 ), sulfate of hydrogen (HSO4 ), acetate ions (CH3COO ), and / or formate ions (HCOO-). If R is an alkane chain having between 8 and 20 carbon atoms, preferably A comprises two halide ions, for example two chloride ions, thus having a total charge of -2. If R is a quaternary amine having the formula (Ia) as previously established, preferably A comprises two chloride ions and one bromide ion, thus having a total charge of -3. Preferably, the compound of the preceding formula I has the following formula: Formula II Formula III Referring to formula II, R is a linear saturated alkane chain having 10 carbon atoms; and A has two chloride ions. Referring to formula III, R is a quaternary amine, in which Ra and Rb are each linear saturated alkane chains having 10 carbon atoms, and A has two chloride ions and one bromide ion. In another procedure of the invention, a compound is provided which has the following formula: Formula IV Where R is an alkane chain having between 8 and 20 carbon atoms, and A has one or more anions having a total charge of -2; or R is a quaternary amine having the following formula: Where Ra and Rb are each an alkane chain having between 8 and 20 carbon atoms, and A has one or more anions having a total charge of -3; and where X is 2, 4, 6, 8 or 10. R can be, for example, a linear or branched saturated alkane chain having between 8 and 18 carbon atoms, for example 8 and 16 carbon atoms, for example 8 and 14 carbon atoms, for example 9 and 15 carbon atoms, for example 10 carbon atoms. Preferably, R is a linear saturated alkane chain having between 8 and 16 carbon atoms, for example 10 carbon atoms. R can be, for example, a quaternary amine according to formula (la), in which Ra and Rb are each linear or branched saturated alkane chains having between 8 and 18 carbon atoms, for example 8 and 16 carbon atoms, for example 8 and 14 carbon atoms, for example 9 and 15 carbon atoms, for example 10 carbon atoms. Ra and Rb can each be a linear or branched saturated alkane chain having a different number of carbon atoms. Preferably, Ra and Rb are each alkane chains Linear saturated compounds that have between 8 and 16 carbon atoms, for example 10 carbon atoms. A saturated linear alkane chain can be represented by the following formula: where n is the number of repeating units that is the number of carbon atoms in the alkane chain linear. Thus, in the case where R is an alkane chain that has between 8 and 20 carbon atoms, it is preferable that R be where n is between 8 and 16 For example, 10. In the case that R is a quaternary amine having the formula (Ia) as 10 As previously established, it is preferable that Ra and Rb be where n is between 8 and 16 for example 10. A may include, for example, halide ions, such as chloride ions (Cl-), bromide ions (Br-), iodide ions (I-), and / or fluoride ions (F-). A may also include, for example, ions of other organic and inorganic acids, such as sulfate (SO42-), carbonate (CO32-), hydrogen carbonate (HCO3-), sulfate of hydrogen (HSO4-), acetate (CH3COO-), and / or formate ions (HCOO-). If R is an alkane chain having between 8 and 20 carbon atoms, preferably A comprises two halide ions, for example two chloride ions, thus having a total charge of -2. If R is a quaternary amine having formula (Ia) as stated above, Preferably A comprises two chloride ions and one bromide ion, thus having a total charge of -3. Preferably, the compound of the preceding formula IV has the following formula: 11 formula (VI) where X is 4, 8 or 10. Referring to formula V, R is a linear saturated alkane chain having 10 carbon atoms; and A has two chloride ions. Referring to formula VI, R is a quaternary amine, in which Ra and Rb are each saturated linear alkane chains having 10 carbon atoms, and A has two chloride ions and one bromide ion. The applicant has found that the preceding compounds represented by formulas I-VI demonstrate remarkable antibacterial and antifungal activity. Without being bound by any particular theory, it is assumed that this antibacterial and antifungal activity may derive from the combination of the aromatic groups thymol and carvacrol, quaternary ammonia groups, and long-chain alkyl groups. Additionally, the complex compounds, according to the 12 Formulas I-III with bromine can further enhance their antibacterial and antifungal properties. Additionally, based on computer modeling, the applicant has found that compounds according to formulas I-VI, which include a combination of the thymol, carvacrol, quaternary ammonium, and long-chain alkane groups, may have antiviral activity, being effective against, for example, the Herpes virus, for example, Herpes Simplex virus and Human Papillomavirus. Without being tied to any particular theory, it is predicted that compounds of formulas I-VI should be capable of possessing direct antiviral activity against viral particles prior to the virus's target cell interaction due to chemical interaction with key biological macromolecules such as proteins, lipids, and nucleoproteins. Compounds of formulas I-VI should be able to disrupt the early stages of viral activity and concentrate on cell interaction, including viral attachment, cell receptor interaction, and viral entry into the cell. Compounds according to formulas I-VI should be potent as inducers of apoptotic cell death during interaction with virus-infected intracellular cells. 13 In another aspect of the invention, a pharmaceutical composition (for example, a human pharmaceutical composition and / or a veterinary pharmaceutical composition) is provided, comprising a compound according to formulas I to VI above. The pharmaceutical composition may be in a form suitable for one or more administrations by oral, rectal, parenteral, transdermal, intravenous, or intra-arterial routes. intraosseous infusion, intracerebral, intracerebroventricular, intrathecal, intramuscular, subcutaneous, intravaginal, intraperitoneal, epidural, intracerebral, intraosseous, intravitreal, transmucosal, buccal or nasal infusion. The pharmaceutical composition may comprise a compound According to formulas I to VI, a pharmaceutically acceptable vehicle, such as an aqueous solution, non-toxic excipients, including salts and preservatives, buffers, and the like. Examples of suitable aqueous and non-aqueous pharmaceutical vehicles, diluents, solvents, or carriers include water, ethanol, polyols (such as glycerol, propylene glycol, polyethylene glycol, and the like), carboxymethylcellulose and suitable mixtures thereof, vegetable oils (such as olive oil), and injectable organic esters such as ethyl oleate. Examples of pharmaceutically acceptable excipients include anti-adherents, binders, coatings, colorants, disintegrants, flavorings, gluing agents, lubricants, Preservatives, absorbents, and sweeteners. 14 3516003 14 of 46 The pharmaceutical compositions of the present invention may also contain additives such as, by way of example, preservatives, wetting agents, emulsifying agents, surfactants, and dispersing agents. Antibacterial and antifungal agents may be included to prevent microbial growth and include, for example, m-cresol, benzyl alcohol, parabens, chlorobutanol, phenol, sorbic acid, and the like. If a preservative is included, benzyl alcohol, phenol, and / or m-cresol are preferred; however, the preservative is by no means limited to these examples. It is also recommended to include isotonic agents such as sugars, sodium chloride, and the like. A pharmaceutical composition suitable for oral administration may be in the form of, for example, a tablet, a pill, a sugar-coated agent, a powder, a capsule, a liquid, a gel, a syrup, an aqueous solution, a suspension, a pill, and the like. The composition may comprise a pharmaceutically acceptable vehicle, for example, liposomes, lactose, trehalose, sucrose, mannitol, xylitol, crystalline cellulose, chitosan, calcium carbonate, talc, titanium oxide, silica, and the like. The pharmaceutical composition can be obtained, for example, by combining the compounds of the invention with a solid excipient, pulverizing the mixture (if necessary) and inserting it into a capsule, for example, a soft capsule. sealed, consisting of a gelatin capsule, gelatin and 15 coating (e.g., glycerol or sorbitol) or a capsule composition suitable for vegetarians. In the soft capsule, the composition may be dissolved or suspended in a suitable liquid, such as a fatty oil, liquid paraffin, or liquid polyethylene glycol, with or without a stabilizer. In another aspect of the present invention, a compound or pharmaceutical composition is provided as previously specified for use as a medicament. In another aspect of the present invention, a compound or pharmaceutical composition as previously specified is provided for use in the treatment of Herpes virus, Human Papillomavirus, bacterial infections and / or fungal infections. The Herpes virus can be one or more of the Herpes Simplex virus, Herpes Simplex virus 1 (HSV-1), Herpes Simplex virus 2 (HSV-2), Varicella zoster virus (VZV), Epstein-Barr virus, Cytomegalovirus, Roseolovirus, Kaposi's Sarcoma-associated herpesvirus, Animal Herpesvirus, such as Pseudorabies virus and Bovine Herpesvirus 1. Preferably, the Herpes virus is a Herpes Simplex virus (e.g., Herpes Simplex virus 1 or Herpes Simplex virus 2) or Cytomegalovirus. Bacterial infections can include those caused by gram-positive bacteria and / or gram-negative bacteria. 16 Bacterial infections can be caused by, for example, the Staphylococcus aureus bacteria and / or the Salmonella enterica bacteria. Fungal infections can be superficial mycoses, cutaneous mycoses, subcutaneous mycoses and / or systemic mycoses. Fungal infections can be caused by, for example, Candida albicans. In another aspect of this invention, the use of a compound or pharmaceutical composition as previously specified is provided in the preparation of a drug to treat the Herpes virus, the Human Papillomavirus, bacterial infections and / or fungal infections. The herpes virus may be one or more of the following: Herpes Simplex virus, Herpes Simplex virus 1 (HSV-1), Herpes Simplex virus 2 (HSV-2), Varicella Zoster Virus (VZV), Epstein-Barr virus, Cytomegalovirus, Roseolovirus, Kaposi's sarcoma-associated herpesvirus, animal herpesvirus such as Pseudorabies virus and Bovine Herpesvirus 1. Preferably, the Herpes virus is a Herpes Simplex virus (e.g., Herpes Simplex Virus 1 or Herpes Simplex Virus 2) or Cytomegalovirus. Bacterial infections can include those caused by gram-positive and / or gram-negative bacteria. Bacterial infections can be caused by, for example, Staphylococcus aureus and / or Salmonella enterica bacteria. 17 Fungal infections can be superficial mycoses, cutaneous mycoses, subcutaneous mycoses, and / or systemic mycoses. Fungal infections can be caused by, among other things. For example, Candida albicans. In another aspect of the invention, a method is provided to treatment of Herpes virus, Human Papillomavirus, bacterial infections and / or fungal infections, comprising a step of administering to a subject a compound or pharmaceutical composition as specified above. The herpes virus can be one or more of the following: Herpes Simplex virus, Herpes Simplex virus 1 (HSV-1), Herpes Simplex virus 2 (HSV-2), Varicella-zoster virus (VZV), Epstein-Barr virus, Cytomegalovirus, Roseolovirus, Kaposi's Sarcoma-associated Herpesvirus, Animal Herpesvirus such as Pseudorabies virus and Bovine Herpesvirus 1. Preferably, the herpes virus is a Herpes Simplex virus (e.g., Herpes Simplex virus 1 or Herpes Simplex virus 2) or Cytomegalovirus. Bacterial infections can include those caused by gram-positive and / or gram-negative bacteria. Bacterial infections can be caused by, for example, Staphylococcus aureus and / or Salmonella enterica bacteria. Fungal infections can be superficial mycoses, cutaneous mycoses, subcutaneous mycoses and / or systemic mycoses. 18 Fungal infections can be caused by, for example, Candida albicans. In another aspect of the invention, a process is provided for the production of the compounds specified above in formulas I-III, comprising the following steps: i) react carvacrol with R2CH2COCl to form a compound which has the formula: (formula VII), where R2 is a halogen, for example chlorine or bromine; react the compound that has the formula the compound that has the formula (formula (formula VIII) with the formula VII) to form the compound that has where R is carbon; or formula: (formula IX), an alkane chain that has between 8 and 20 R is a quaternary amine that has the atoms of following 19 (Ia) where Ra and Rb are each an alkane chain that has between 8 and 20 carbon atoms; iii) react thymol with R2CH2COCl to form a compound that has the formula (formula X), where R2 is a halogen, for example chlorine or bromine; v) react the compound that has the formula (formula IX) with the compound that has the formula (formula X) to form the product final that has the formula 20 (Formula I) where R is an alkane chain having between 8 and 20 carbon atoms; and A is one or more anions having a total charge of -2; or R is a quaternary amine having the following formula: (Ia) where Ra and Rb are each an alkane chain having between 8 and 20 carbon atoms, and A is one or more anions having a total charge of -3. R can be, for example, a linear or branched saturated alkane chain having between 8 and 18 carbon atoms, for example 8 and 16 carbon atoms, for example 8 and 14 carbon atoms, for example 9 and 15 carbon atoms, for example 10 carbon atoms. Preferably, R is a linear saturated alkane chain having between 8 and 16 carbon atoms, for example 10 carbon atoms. 21 R can be, for example, a quaternary amine according to formula (a), wherein Ra and Rb are linear or branched saturated alkane chains having between 8 and 18 carbon atoms, for example, 8 and 16 carbon atoms, for example, 8 and 14 carbon atoms, for example, 9 and 15 carbon atoms, for example, 10 carbon atoms. Ra and Rb can each be linear or branched saturated alkane chains having a different number of carbon atoms. Preferably, Ra and Rb are each linear saturated alkane chains having between 8 and 16 carbon atoms, for example, 10 carbon atoms. A saturated linear alkane chain can be represented by the following formula: where n is the number of repeating units that is the number of carbon atoms in the linear alkane chain. Thus, in the case where R is an alkane chain that has between 8 and 20 carbon atoms, it is preferred that R be where n is between 8 and 16, for example 10. In the case that R be a quaternary amine that has the formula (Ia) as follows 22 specified beforehand, Ra and Rb are preferred. where n is between 8 and 16, for example 10. If R is an alkane chain with between 8 and 20 carbon atoms, the process may include another step of . R . Ri reaction of a compound that has the formula (formula XI) with four molar equivalents of dimethylamine to form a ditertiary amine having the following formula (formula VI), where Rc is an alkane chain having between 8 and 20 carbon atoms, and R1 is a halogen, for example bromine or chlorine; and R is an alkane chain having between 8 and 20 carbon atoms. In the case that R is a quaternary amine that has the following formula: (Ia) where Ra and Rb are each an alkane chain that has between 8 and 20 carbon atoms, the process may include another stage of 23 . R . Ri reaction of a compound that has the formula (formula XI) with three molar equivalents of dimethylamine to form a quaternary amine that has the following formula (formula Ib), where Rc is an alkane chain having between 8 and 20 carbon atoms and R1 is a halogen, for example bromine or chlorine; and where Ra and Rb are each an alkane chain having between 8 and 20 carbon atoms. The reactions in stages II and IV can both occur at a temperature of -10°C. The process also comprises one or more separation or extraction steps; for example, a separation step may include column chromatography, low-pressure liquid chromatography, high-performance liquid chromatography, and the like. Purification steps may include standard purification processes known in the art, for example, filtration, evaporation, liquid-liquid extraction, crystallization, absorption, recrystallization, chromatography, distillation, and the like. In another aspect of the invention, a process is provided for the production of a compound having the formulas IV-VI, as 24 It is specified beforehand, understanding the process of reacting (e.g., complexing agent) the compound that has the formula form the compound (Formula I) with bromine for has the formula that (formula IV) has where R is an alkane chain that between 8 and 20 atoms of carbon, and A is one or more anions that they have a total load of -2; or R is a quaternary amine which has the following formula: (Ia) where Ra and Rb are each an alkane chain that has between 8 and 20 carbon atoms, and A is one or more anions that have a total charge of -3. 25 In another aspect of the invention, a process is provided for the production of a compound substantially as described herein with reference to Figure 1, Figure 2 or Figure 3. In another aspect of the invention, a compound is provided that has the following formula: (formula I) where R is an alkane chain having between 8 and 20 carbon atoms; and A is one or more anions having a total charge of -2; or R is a quaternary amine having the following formula: / RbV \ + (the) where Ra and Rb are each an alkane chain having between 8 and 20 carbon atoms, and A is one or more anions having a total load of -3; and where the compound optionally forms a complete form with bromine. 26 The present invention will now be described in more detail with reference to the accompanying graphics, Figures 1 to 7, in which Figure 1 illustrates an example process for the synthesis of a compound of the invention. Figure 2 illustrates an example process for the synthesis of another compound of the invention. Figure 3 illustrates an example process for the synthesis of another compound of the invention. Figure 4 illustrates the results of cytotoxicity analyses of a compound of the invention at concentrations between 0 gg / mL and 50 gg / mL in Vero cells, and the effect of a compound of the invention on the diffusion of Herpes Simplex Virus 1 and plaque formation in Vero cells. Figure 5 illustrates the results of cytotoxicity analyses of another compound of the invention at concentrations between 0 gg / mL and 100 gg / mL in Vero cells, and the effect of another compound of the invention on the diffusion of Herpes Simplex Virus 1 and plaque formation in Vero cells. Figure 6 illustrates the results of cytotoxicity analyses of another compound of the invention at concentrations between 0 gg / mL and 100 gg / mL in Vero cells. 27 Figure 7 illustrates the results of the effect of the compounds of the invention in the formation of virus plaque Vaccinia in BSC cells 40. Process for producing the compounds of the invention. Compound 2. N1-{2-]2-methyl-5-(propan-2-yl)phenoxy]-2-oxoethyl}-N1,N1,N10,N10-tetramethyl- -N10-{2[5-methyl-2-(propan-2-yl)phenoxy]-2oxoethyl} decane-1-,10-bis(amino) dichloride Figure 1 shows an example process for synthesizing Compound 2, which is a compound of the invention defined by the preceding Formula II. In a first step, 1,10-Dibromodecane (Compound 5) is reacted with 4 molar equivalents of dimethylamine to to form 1,10-Bis(dimethylamino)decane (Compound 6). The reaction occurs at 4-5°C in benzene and continues with a step of Acid extraction followed by alkaline treatment and diethyl ether extraction. The extracted fractions are dried over magnesium sulfate and then purified by vacuum distillation. In a second step, Carvacrol (2-Methyl-5-(1-methylethyl)phenol) (Compound 7) is reacted with chloroacetyl chloride to form Compound 8. The reaction is carried out at -10°C 28 The mixture is heated for 1 hour and then stirred at room temperature for 5 hours. The reaction mixture is then washed with acid, followed by treatment with sodium bicarbonate and then water. The organic layer is dried over sodium sulfate, filtered, and the solvent is removed under vacuum. In a third step, Compound 8 is reacted with 1,10-bis(dimethylamino)decane (Compound 6) to form Compound 9. The reaction is carried out by boiling Compound 6 and Compound 8 in benzene for 15 minutes and then allowing the reaction mixture to stand at room temperature for 24 hours. Ethyl acetate is then added to the reaction mixture, the upper layer is removed, and the lower layer is isolated as residue. The residue (containing Compound 9) is then used in the fifth step. In a fourth step, thymol (2-isopropyl-5-methylphenol) (Compound 10) is reacted with chloroacetyl chloride to form Compound 11. The reaction is carried out at -10°C for 1 hour and then stirred at room temperature for 5 hours. The reaction mixture is then washed with acid, followed by treatment with sodium bicarbonate and then water. The organic layer is dried in sodium sulfate, filtered, and the solvent is removed under vacuum. In a fifth stage, the residue from the third stage (containing Compound 9) reacts with compound 11 29 To form the final product: Compound 2. The reaction is carried out by boiling Compounds 9 and 11 in benzene for 15 minutes and then leaving the reaction mixture at room temperature for 24 hours. Ethyl acetate is then added to the reaction mixture, the top layer is removed, and the bottom layer is isolated as a residue. The resulting residue is then dissolved in acetone and Compound 2 is precipitated by adding diethyl ether. It would be appreciated if other purification and separation stages were also included in the process, for example between each of the preceding stages and also after the process is completed to purify the final compound (Compound 2). The separation steps may include column chromatography, low-pressure liquid chromatography, high-performance liquid chromatography, and similar processes. The purification steps may include standard purification processes known in the art, such as filtration, evaporation, liquid-liquid extraction, crystallization, absorption, recrystallization, chromatography, distillation, and similar processes. Compound 2 was isolated as a brown hygroscopic powder, with the following properties. 30 Appearance: Brown hygroscopic powder Molecular formula: C38H62N2O4C12 Molecular weight: 681.81 gmol-1 Melting point: 92-96 C Aqueous solution pH= 6 Solubility: soluble in water, acetone, acetonitrile, sulfoxide dimethyl (DMSO); insoluble in diethyl ether, ethyl acetate and hexane. 1H NMR (DMSO / CCl4-1 / 3) 5 1.18(d,6H,-CH3),1.22(d,6H,-CH3), 1.37- 1.40(m,12H,-CH2-),1.81-1.85(m,4H,-CH2-),2.17(s,3H,Ar-CH3),2.32 (s,3H,Ar-CH3),2.87(q,1H,-CH),3.04(q,1H,-CH),3.47(s,12H,+N (CH3)2),3.80-3.85(m,4H,+N-CH2-),5.33(s,4H,-(C=O)-CH2-N+),6.96-7.02(m,4H,Ar-H),7.16-720(m,2H,Ar-H). Compound 4 Di-bromine complex N1-{2-[2-methyl-5-(propan-2-yl)phenoxy]-2-oxoethyl}-N1,N1,N10,N10-{2-[5-methyl1-2-(propan-2-yl)phenoxy]-2oxoethyl}decane-1,10-bis amino) dichloride 31 Figure 2 shows an example process for synthesizing Compound 4, which is another compound of the invention and is defined by the preceding formula V. Compound 2 was synthesized according to the process specified above for Compound 2. After the formation of Compound 2, Compound 2 reacted with bromine to form Compound 4. As specified above for Compound 2, it will be appreciated if other purification and separation stages are also included in the process, for example between each of the preceding stages and also after the process is complete to purify the final compound (Compound 4). The separation steps may include column chromatography, low-pressure liquid chromatography, high-performance liquid chromatography, and similar processes. The purification steps may include standard purification processes known in the art, for example, filtration, evaporation, liquid-liquid extraction, crystallization, absorption, recrystallization, chromatography, distillation and the like. Compound 4 was isolated as an orange rubber, having the following properties. Appearance: orange rubber. 32 Molecular Formula: C38H62N2O4Cl2Br4 Molecular Weight: 1001.41 gmol-1 Solubility: soluble in dimethyl sulfoxide (DMSO); insoluble in water. 1H NMR(DMSO / CCl4-1 / 3) 5 1.18-1.22(m,12H,-CH3), 1.37-1.40 (m, 12H,-CH2-),1.81-1.85(m,4H,-CH2-)2.17(s,3H,Ar-CH3),2.32(s,3H,Ar —CH3),2.87(q,1H, -CH),3.04(q,1H, -CH),3.47(s,12H,+N(CH3)2),3.80-3.85(m,4H,+H-CH2-),5.33(s,4H,-(C=O)-CH2-N+),6.96-7.02(m,4H,Ar-H),7.16-7.20(m,2H,Ar-H). Compound 3 Systemic Name: N1-{{2-[2-methyl-5-(propan-2-yl)phenoxy]-(2-oxoethyl)(dimethyl)azaniumyl bromide}decyl}-N10-{2-[5-methyl-2-(propan-2-yl)phenoxy]-2oxoethyl}-N1,N1,N10,N10-tetramethyldecane-1,20-bis(amino) dichloride Figure 3 shows an example process for synthesizing Compound 3, which is a compound of the invention defined by the preceding Formula III. In a first stage, 1,10-Dibromodecane 5 is reacted with 3 molar equivalents of dimethylamine to form Compound 12. The reaction occurs at 4-5°C in benzene and continues with an acid extraction step followed by alkaline treatment and Extraction with diethyl ether. The extracted fractions are dried 33 in magnesium sulfate and then purified by vacuum distillation. In a second step, thymol (2-isopropyl-5-methylphenol) (Compound 10) was reacted with chloroacetyl chloride to form Compound 11. The reaction was carried out at -10°C for 1 hour and then stirred at room temperature for 5 hours. The reaction mixture was then washed with acid, followed by treatment with sodium bicarbonate and then water. The organic layer was dried in sodium sulfate, filtered, and the solvent was removed under vacuum. In a third step, Compound 11 is reacted with Compound 12 to form Compound 13. The reaction is carried out by boiling Compounds 11 and 12 in benzene for 15 minutes and then leaving the reaction mixture at room temperature for 24 hours. Ethyl acetate is then added to the reaction mixture, the upper layer is removed, and the lower layer is isolated as a residue. The residue (containing Compound 13) is then used in the fifth step. In a fourth step, carvacrol (2-methyl-5-(1-methylethyl)phenol) (Compound 7) is reacted with chloroacetyl chloride to form Compound 8. The reaction is carried out at -10°C for 1 hour and then stirred at room temperature for 5 hours. The reaction mixture is then washed with acid, followed by treatment with sodium bicarbonate and then 34 water. The organic layer is dried in sodium sulfate, filtered and the solvent is removed under vacuum. In a fifth step, the residue from the third step (containing Compound 13) is reacted with Compound 8 to form the final product: Compound 3. The reaction is carried out by boiling Compounds 8 and 13 in benzene for 15 minutes and then leaving the reaction mixture at room temperature for 24 hours. Ethyl acetate is then added to the reaction mixture, the top layer is removed, and the bottom layer is isolated as a residue. The residue is then dissolved in acetone and Compound 3 is precipitated by adding diethyl ether. It would be appreciated if other purification and separation stages were also included in the process, for example between each of the preceding stages and also after the process is completed to purify the final compound (Compound 3). The separation steps may include steps for performing column chromatography, low-pressure liquid chromatography, high-performance liquid chromatography, and similar techniques. The purification steps may include standard purification processes known in the art, for example, filtration, evaporation, liquid-liquid extraction, 35 crystallization, absorption, recrystallization, chromatography, distillation and the like. Compound 3 was isolated as a brown hygroscopic powder, with the following properties. Appearance: brown hygroscopic powder. Molecular Formula: C50H88N3O42ClBr Molecular Weight: 946.06 gmol-1 Melting point: 75-78 °C Aqueous solution pH= 7.2 Solubility: soluble in water, acetone, dimethyl sulfoxide (DMSO); insoluble in diethyl ether and ethyl acetate. Exhibits surfactant activity 1H NMR (DMSO / CCl4-1 / 3) 5 1.18-1.23(m,12H,-CH3), 1.38-1.42 (m, 24H,-CH2-),0-1.80-1.84(m,8H,-CH2-),2.18(s,3H,Ar—CH3),2.34(s, 3H,Ar-CH3)2.90-3.10(m,2H,-CH),3.45-3.50(m,18H,+N(CH3)2),3.75- 3.80(m,8H,+N-CH2-),5.22(s,4H,-(C=O)-CH2-N+),6.96-7.02(m,4H,Ar- H),7.16-7.20(m,2H,Ar-H). Example 1 Compounds 2, 3, and 4 were analyzed for anti- activity antibacterial and antifungal. 36 The minimum inhibitory concentration (MIC) of each compound was analyzed using the broth dissolution assay. Teams. McFarland standard 0.5 Falcon 5ml Round Bottom Tubes Disposable rings (1 pl and 10 pl) Graduated pipettes (20 pl - 1000 pl) Disposable Petri dishes Media Sterile normal saline solution TSB (Triple Soybean Broth) TSA (Tryptic Soy Agar) Bacterial and Fungal Strains Salmonella enterica serovar Typhimurium ATCC 14028 Staphylococcus aureus ATCC 6538 Candida albicans ATCC 10231 Compounds 2, 3 and 4 were diluted in dimethyl sulfoxide (DMSO) at 10 mg / ml and were diluted twice for future analysis in TSB. Method D^a 1 Inoculum standardization 37 From a pure o / n culture, material with at least 3-4 colonies was selected and fully suspended in 4 ml of saline solution. in tubes. The suspension was mixed. The turbidity of the inoculum was adjusted to match that of the standard visually comparing with the McFarland 0.5 standard using white paper with black lines as a background. The McFarland 0.5 suspension was diluted as follows for the species analyzed in this course: Gr-neg.: 10 pl McFarl. 0.5 and 10 ml of broth Gr-pos.: 50 pl McFarl. 0.5 in 10 ml of broth The suspensions were used for inoculation within 15 minutes. Inoculation and incubation 5 ml Falcon round-bottom tubes were inoculated with 500 ml of the inoculum suspension with 500 ml of twice dilutions of antimicrobial agent using a graduated pipette. The tubes were sealed and incubated at 37°C for 18–22 hours. This was done to avoid losing culture media and to prevent cross-contamination. A McFarland 0.5 is approximately 10⁸ CFU / ml. Standardization of the inoculum is essential because the interpretation of the results is based on a specific inoculum. Each tube contained approximately 5 x 10⁵ - 1 x 10⁶ CFU / ml after from bacterial inoculation and 5x103- 1x104 CFU / ml of yeast. 38 D^a 2 The purity of the inoculum suspension was verified. The development was verified in the 3 positive control tubes. The minimum inhibitory concentration (MIC) was recorded as the lowest concentration of antimicrobial agent without any visible growth. The results are specified in Table 1 below. In summary, all the compounds analyzed demonstrated potent antifungal activity against Candida albicans, as well as antibacterial activity against Staphylococcus aureus and Salmonella enterica serovar Typhimurium. Crops Count of Cells Bacterial / yeast (cfu / ml)# MIC of Samples (pg / ml)1 Compound 2 Compound 3 Compound 4 6x103 62.5-125* 31.25-62.5 31.25-62.5 Candida 3x103 62.5-125 31.25-62.5 31.25-62.5 albicans ATCC 6x103 62.5-125 31.25-62.5 31.25-62.5 10231 6.5x103 62.5-125 31.25-62.5 31.25-62.5 Staphylococcus 2.1x106 31.25-62.5 15.6-31.25 15.6-31.25 39 aureus ATCC 1.2x106 31.25-62.5 15.6-31.25 31.25-62.5 6538 2x106 31.25-62.5 15.6-31.25 15.6-31.25 1.4x106 31.25-62.5 15.6-31.25 15.6-31.25 Salmonella 62.5-125 31.25-62.5 31.25-62.5 enteric 62.5-125 31.25-62.5 31.25-62.5 serovar 5x105 62.5-125 31.25-62.5 31.25-62.5 Typhimurium 62.5-125 31.25-62.5 31.25-62.5 ATCC 14 028 Table 1: Antimicrobial activity of different samples analyzed in indented experiments (n=4) using the dissolution broth method. # Represents bacterial / yeast cell count (CFU / ml) analyzed in 2 replicates in 4 experiments indented. * The numbers in bold correspond to the final bacterial / yeast cell titer detection. This means that the numbers in bold represent the bactericidal concentration, while the numbers in regular text are the bacteristatic concentration of the compounds on the MIC scale. 40 1. Determination of the MIC by dissolving broth using Sensitive. 4th Ed. April 2003 Edited by: Rene S. Hendriksen (DFVF) Example 2 The antiviral effect and cytotoxicity of the compounds of the invention were investigated using analytical compounds 2, 3 and 4 in different mammalian cell lines. Materials and Methods Cells and Viruses Both Herpes Simplex Virus 1 (HSV 1) and Vaccinia virus (VV), and the cell lines used included HeLa, BSC 40 and Vero cells. HeLa, Vero and BSC 40 cells were cultured in Eagel medium Modified Dulbecco (DMEM) supplemented with 10% fetal bovine serum (FBS) and 1% penicillin / streptomycin (Gibco) in a 5% CO2 incubator at 37°C. The Western Reserve strain of Vaccinia Virus (WR-VV) is Amplified in BSC40 cells, titrated and stored at -80°C. The Herpes Simplex Virus 1 (HSV-1) was amplified in cells Vero, it was titled and stored at -80°C. Compounds and reagents Compounds 2, 3, and 4 (in powder form) were dissolved in Absolute ethanol was used to obtain standard solutions at a concentration of 0.2 g in 1 mL. Aliquots were stored at - 41 20°C. Before the experiments, a new series dissolution is made in free-growing serum medium (DMEM). Cytotoxicity The cytotoxic effect of the chemicals on HeLa, BSC40, and Vero cells was analyzed. The cells were seeded in 12 wells of trays, so that the trays had 80% confluence the following day. Compounds 2, 3, and 4 were applied to the cells at varying concentrations. After 30 minutes of pre-treatment, the growth medium was added to the cells in the presence of the same concentration of compounds 2, 3, and 4. The Cells were collected daily, fixed, and stained 48 or 72 hours after treatment, and then photographed. All samples were fixed with 4% formaldehyde in H2O for 20 minutes at room temperature and subsequently stained with Crystal Violet for 30 minutes at room temperature. Virus infections and plaque assay Freshly confluent cells were infected with WR-VV and HSV-1 (approximately 200 to 300 PFU per well in a 6-well or 12-well tray) at 37°C for 1 hour. The cells were washed and cultured in growth medium containing 1% agarose, and fixed 2 days post-infection. Alternatively, the cells were pre-treated with serum-free Dulbecco Modified Eagle Medium (DMEM) or DMEM containing 42 3516003 42 of 46 Different concentrations of the compounds were used before infection, and compounds 2 and 3 remained in cultures throughout the experiment until the cells were fixed as described above. In some experiments, a liquid plate assay without agar was performed. Results Cytotoxicity of compounds in different mammalian cell lines In order to analyze the antiviral effect of compounds 2, 3 and 4, an appropriate solution of the compounds, such as the fact that the compounds were non-toxic to cells and that cell viability was not affected. A variety of compound concentrations were analyzed in different mammalian cell lines such as HeLa, BSC40 and Vero cells. Cells cultured overnight were pre-treated with high to low doses of compounds 2, 3, and 4 in a medium of serum-free for 30 minutes. The medium was then replaced with normal growth medium containing compounds 2, 3 and 4 of the entire experiment. The cells were monitored daily for up to 72 hours, then fixed, stained, and photographed. As shown in Figures 4, 5, and 6, this The experiment revealed that for all 3 compounds, the Cells tolerate compounds 2, 3, and 4 at concentrations of 25 to 100 pg / ml. The rows marked C in each of the Figures 4 and 5, and Figure 6 illustrate the results of the 43 3516003 43 of 46 treatment of Vero cells, which were not infected with HSV 1, and treated with compounds 2, 3 and 4. HSV 1 diffusion and viral plaque formation. The inhibitory effect of compounds 2 and 3 on Vero cells was monitored. Cells were pre-treated with different concentrations of compounds 2 and 3, and subsequently treated with buffer or buffer containing HSV-1. After two days of infection, the cells were fixed, stained, and photographed. To determine whether the compounds could inhibit viral diffusion of HSV-1 or plaque formation, a liquid plaque assay was performed to determine diffusion (Row A in Figures 4 and 5), as well as an agar assay to determine the number of plaques (Row B in Figures 4 and 5). A strong inhibitory effect was observed for compounds 2 and 3, as shown in Figures 4 and 5, respectively. Both compounds effectively reduced HSV-1 diffusion and the number of plaques in Vero cells in a dose-dependent manner. Compounds 2 and 3 had no inhibitory effect on Vaccinia virus plaque formation. To analyze the specificity of compounds 2 and 3 against HSV-1, the compounds were also tested against Vaccinia virus, another DNA virus. BSC 40 cells were either preserved untreated or pre-treated with the compounds at a concentration of 50 mg / ml, and then the cells were They were infected with the Vaccinia virus and monitored side by side. 44 throughout the experiment. As shown in Figure 7, none of compounds 2, 6, and 3 inhibited the formation of Vaccinia virus (VV) plaques indicating that the inhibitory effect of compounds 2 and 3 on HSV 1 infection is highly specific. From the experiments mentioned above, it can be concluded that all the cells analyzed can tolerate compounds 2, 3, and 4 at concentrations of 0 to 100 pg / ml. Compounds 2 and 3 both demonstrate a strong antiviral effect against HSV-1-infected Vero cells, both in terms of virus diffusion and plaque formation. At 50 pg / ml of the compounds, infectivity was reduced by 50%. At 100 pg / ml of the compounds, infectivity was reduced by 80%. None of the compounds analyzed are active against Vaccinia virus. 45 NELSON BIEDMA - 20247533983 Digitally signed by PORTALTRAMITES - INPI Date: 2025.11.17 15:42:47 -03:00 Reason: Digitally Signed by the INPI Location: Buenos Aires, Argentina

Claims

1. A compound characterized in that it has the following formula: (FORMULA I) where R is an alkane chain having between 8 and 16 carbon atoms, and A is one or more anions having a total charge of -2; or R is a quaternary amine having the following formula: (FORMULA Ia) where Ra and Rb are each an alkane chain having between 8 and 16 carbon atoms, and A is one or more anions having a total charge of -3. 10 Claims follow