Pyrvinium-derived compounds and uses thereof

Abstract

The present invention relates to compounds of general formula (I), or to a pharmaceutically acceptable salt thereof, as well as to their therapeutic use, particularly as antibiotic and / or antiparasitic agents. The present invention likewise discloses pharmaceutical compositions comprising said compounds. Formula (I)

Description

[0001] PYRVINIUM DERIVATIVES AND THEIR USE The present invention relates to pyrvinium derivatives and their use in therapy, and therefore falls within the field of medicine. BACKGROUND OF THE INVENTION The trypanosomatid parasites Trypanosoma brucei, Trypanosoma cruzi, and Leishmania spp. are pathogenic to humans. These parasites cause African trypanosomiasis or sleeping sickness, American trypanosomiasis or Chagas disease, and leishmaniasis (in its various clinical manifestations: visceral, cutaneous, and mucocutaneous), respectively. These protozoa have life cycles that alternate between two hosts: an insect vector and a mammalian host. In the insect, the procyclic (T. brucei), epimastigote (T. cruzi) and promastigote (Leishmania) forms are extracellular, whereas in the mammalian host, the amastigote forms of Leishmania spp. and T.T. cruzi develops intracellularly, except for the extracellular forms of T. brucei. The fight against these diseases relies on a highly toxic, outdated, and ineffective pharmacological arsenal against which clinical resistance has developed. Antibiotic resistance has become a major challenge to global health and represents one of the most formidable obstacles in contemporary medical science. This problem is exacerbated by the limited number of new antimicrobial agents approved, many of which are merely chemical modifications of existing antibiotics. Such modifications often fail to circumvent established resistance mechanisms present in bacterial genomes, leading to the rapid emergence of new resistant strains. This context underscores the urgent need to identify new antimicrobial compounds.These compounds must have a unique mode of action and target multiple therapeutic sites, thus minimizing the potential for resistance development while ensuring high specificity to mitigate side effects. Pyrvinium, a red fluorescent dye, is described in US2515912. It is a small, lipophilic compound with multiple amino groups and a positive charge at physiological pH. See also Welch et al., Science 1947, May 9;105(2732):486-8; Peters et al., J. Pharmacol. Exp. Ther. 1949, 96, 460–471; Hales, DR and Welch, AD, J. Pharmacol. The anthelmintic activity (against parasitic worms) of cyanine dyes, chloride salt, and pyrvinium pamoate is described in Exp. Ther. 1953, 107, 310–314. The potential use of pyrvinium pamoate against viral infections is described in Shen et al., J. Virol. 2019, 93, e00023-19; and Glanz et al., Viruses, 2020, 12, 442. Niu et al.The potential use of pyrvinium pamoate against bacterial infections caused by Staphylococcus aureus and Mycobacterium tuberculosis is described in Pathogens, 2017, 6, 44; Guan et al., Emerg. Microbes Infect. 2020, 9, 302–312. The potential use of pyrvinium pamoate against infections caused by the protobacteria Bartonella henselae is described in Li et al., Antibiotics, 2019, 8, 50. Kaul et al., Future Microbiology, Vol. 17, No. 18, published online: 31 Oct 2022 (https: / / doi.org / 10.2217 / fmb-2022-0159) and Microb. Spectr.2021, Volume 9 (3), e00951-21, describes the synergy of pyrvinium pamoate with levofloxacin and fluoroquinolone, respectively, against infections caused by Staphylococcus aureus. Teguh et al., J. Med. Chem. 2013, 56, 6200–6215, describes the potential use of pyrvinium pamoate and derivatives against infections caused by Plasmodium spp. Gaikwad et al., Bioorg. Med. Chem. Lett.In 2020, 30, 127037, the use of pyrvinium derivatives against Plasmodium falciparum and Mycobacterium tuberculosis infections is described. Documents US2008 / 0293766 and WO2017 / 041040 describe pyrvinium derivatives as androgen receptor inhibitors and their potential use against different types of cancer. The present invention presents novel pyrvinium derivatives conjugated with carbohydrate units. The high toxicity of pyrvinium pamoate is one of the main drawbacks to its therapeutic use. The novel glycosylated pyrvinium derivatives exhibit lower toxicity than pyrvinium pamoate, both at the cellular level and in animal models, such as zebrafish. Another advantage of the new glycosylated pyrvinium derivatives is that they show greater efficacy and a wider therapeutic window than pyrvinium pamoate in their use as an antiparasitic and antibacterial agent.DESCRIPTION OF THE INVENTION The present invention discloses novel compounds that are pyrvinium derivatives in which a substituent has been included on the terminal phenyl group. Among the substitutions is a triazole ring, which, in turn, is linked to other substituents such as carbohydrates. The invention also relates to pharmaceutical compositions comprising the novel compounds and their use in therapy. Pyrvinium pamoate has the following formula: The modifications made to it, disclosed in the present invention, have allowed for improved uptake in parasites and bacteria through potential carbohydrate receptors and transporters, or through its improved interaction with cell membranes. A first aspect of the present invention relates to a compound of general formula (I): where: R1 is a -NH2 or -NR3R4 group, where R3 and R4 are independently a C1-C5 alkyl or R3 and R4 together with the N to which they are attached form an aromatic or aliphatic heterocycle of between 5 and 7 members; R2 is a glycosyl radical, where the glycosyl is selected from monoglycosyl, diglycosyl and triglycosyl, A is a group selected from -(CH2) n -, -(OCH2CH2) n - and -(SCH2CH2) n-, where n is an integer between 0 and 4 (in these last two cases group A is joined to R2 through the O or S atom of said group A), X and Y are independently selected from -CH, -CF or -N-, W is a counterion to compensate for the positive charge of the nitrogen of the aromatic ring and q is an integer selected from 1 to 3 such that the positive charges are compensated with the negative charges, the final charge of the compound of formula (I) being zero. In a preferred embodiment of the compounds of the invention (formula (I)), R1 is a –NR3R4 group, where R3 and R4 are independently a C1-C5 alkyl, more preferably, R3 and R4 are methyl. In another preferred embodiment of the compounds of the invention (formula (I)), R1 is a –NR3R4 group, where R3 and R4 together with the N to which they are attached form a heterocycle of between 5 and 7 links, either aromatic or aliphatic.In a more preferred embodiment, the heterocycle includes, in addition to the nitrogen atom to which R3 and R4 are attached, another nitrogen atom or an oxygen atom on the ring. The heterocycle may optionally be substituted with at least one C1-C3 alkyl group. In a preferred embodiment, the heterocycle formed by the –NR3R4 group is a morphollinyl, pyrrolidinyl, or N-methylpiperazinyl group. In a preferred embodiment, the R1 group is located at position 5, 6, 7, or 8 of the quinoline and, more preferably, at position 6, with position 1 being the nitrogen of the quinoline and position 2 being the alkenyl group, as shown below. The compounds of the invention of formula (I) are accompanied by a counterion to counteract the positive charge of the nitrogen in the aromatic ring. The counterion W is preferably selected from halide (F-, Cl-, Br-, or I-), acetate, besylate, benzoate, carbonate, bicarbonate, benzenesulfonate, bitartrate, citrate, stearate, phosphate, fumarate, gluconate, glycolate, hexanoate, hydroxynaphthoate, lactate, mesylate, nitrate, nitrite, octanoate, oleate, pamoate, pantothenate, propionate, polygalacturonate, salicylate, succinate, sulfate, tartrate, theoclate, tosylate, triflate, tetraphenylborate, and trifluoroacetate. Preferably, the counterion W is trifluoroacetate (CF3COO-). In a preferred embodiment of the compound of formula (I), X and Y are selected independently of CH and N. In another preferred embodiment of the compound of formula (I), X and Y are CH. In another preferred embodiment, X is N and Y is CH. In another preferred embodiment, X is CH and Y is N.In a preferred embodiment of the compound of formula (I), n is a number selected from 0 to 3, more preferably from 0 to 2, and even more preferably n is 0 or 1. In a preferred embodiment of the compound of formula (I), the glycosyl radical R2 is selected from monoglycosyl and diglycosyl. Even more preferably, R2 is selected from monoglycosyl. In a preferred embodiment, the glycosyl radical is selected from glucosyl, 6-deoxyglucosyl, 6-deoxy-6-fluoroglucosyl, fucosyl, galactosyl, 2,6-dideoxyglucosyl, mannosyl, xylosyl, maltosyl, isomaltosyl, maltulosyl, cellobiosyl, gentiobiosyl, lactosyl, lactulosyl and sucrosyl, more preferably glucosyl, 6-deoxyglucosyl, 6-deoxy-6-fluoroglucosyl, fucosyl, galactosyl, 2,6-dideoxyglucosyl, mannosyl, xylosyl and maltosyl, the glycosyl being attached to the rest of the molecule by the anomeric carbon or by a carbon other than the anomeric carbon.In a preferred embodiment of the compound of formula (I), n is 0 and R2 is a monoglycosyl radical, preferably selected from glucosyl, 6-deoxyglucosyl, 6-deoxy-6-fluoroglucosyl, fucosyl, galactosyl, 2,6-dideoxyglucosyl, mannosyl, or xylosyl, and which may be attached at the carbon 1 or anomeric position of the glycosyl group or at a carbon other than the anomeric carbon. In a more preferred embodiment of the compound of formula (I), n is 0 and R2 is a monoglycosyl radical, preferably 6-deoxyglucosyl, 6-deoxy-6-fluoroglucosyl, fucosyl, or xylosyl, and more preferably 6-deoxyglucosyl, preferably attached at the anomeric carbon of the glycosyl group to the rest of the molecule. In a preferred embodiment of the compound of formula (I), n is 0 and R2 is a diglycosyl, preferably maltosyl, isomaltosyl, maltulosyl, cellobiosyl, gentiobiosyl, lactosyl, lactulosyl or sucrosyl and more preferably maltosyl, preferably attached by the anomeric carbon of the glycosyl.In a preferred embodiment of the compound of formula (I), A is -(CH2). n -, -(OCH2CH2) n - or -(SCH2CH2) n - n is not zero, preferably n is 1. In a preferred embodiment of the compound of formula (I), A is -(CH2) n -, -(OCH2CH2) n - or -(SCH2CH2) n - , yn is not zero, preferably n is 1, and R2 is a monosaccharide, preferably selected from glucosyl, 6-deoxyglucosyl, 6-deoxy-6-fluoroglucosyl, fucosyl, galactosyl, 2,6-dideoxyglucosyl, mannosyl, or xylosyl, and which may be attached to the rest of the molecule by the anomeric carbon of the glycosyl group or by a carbon other than the anomeric carbon. In a more preferred embodiment of the compound of formula (I), A is -(CH2) n -,- (OCH2CH2) n - or -(SCH2CH2) n- yn is not zero, preferably n is 1, and R2 is a monosaccharide, preferably selected from 6-deoxyglucosyl, galactosyl, 2,6-dideoxyglucosyl or mannosyl, and more preferably galactosyl or mannosyl, preferably linked by the anomeric carbon position of the glycosyl to the rest of the molecule. In a further preferred embodiment of the compound of formula (I), A is -(OCH2CH2) n -yn is non-zero, preferably n is 1, and R2 is galactosyl, preferably linked by the anomeric carbon position of the glycosyl to the rest of the molecule. In a further preferred embodiment of the compound of formula (I), A is -(SCH2CH2) n- yn is not zero, preferably n is 1, and R2 is mannosyl, preferably linked by the anomeric carbon of the glycosyl group to the rest of the molecule. The triazole ring of the compound of formula (I) is located in the para, meta, or ortho position of the aromatic ring with respect to the other substituent of said ring (the triazole ring is not linked to either X or Y, but to any of the other carbons of the aromatic ring). In a preferred embodiment, the compounds of the present invention comprise a structure selected from:

[0002] 5 A second aspect of the invention relates to a compound of formula (I), as described in the first aspect of the invention, for use as a medicament. Another aspect of the invention relates to a compound of formula (I), as described in the first aspect of the invention, for use in the treatment and / or prevention of infections caused by bacteria and / or parasites. In a preferred embodiment of this aspect, the Gram-positive bacteria are selected from: Aerococcus urinae HUSC 230204, Bacillus cereus HUSC 264402, Corynebacterium amycolatum HUSC 256285, Corynebacterium jeikeium HUSC 223612, Corynebacterium urealyticum HUSC 235888, Enterococcus faecalis HUSC 123095, Enterococcus faecium HUSC 263161, and Fadklamia sp.HUSC 263425, Listeria monocytogenes HUSC 765279, Micrococcus luteus UGRA1, Mycobacterium smegmatis UGRA1, Schaalia radingae HUSC 256790, Streptococcus agalactiae HUSC 264551, Streptococcus pyogenes HUSC 42856, Staphylococcus aureus HUSC 263091, Staphylococcus epidermidis HUSC 258042. A more preferred embodiment of this aspect, the bacteria are gram (+) are selected from: Corynebacterium amycolatum HUSC 256285, Corynebacterium jeikeium HUSC 223612, Corynebacterium urealiticum HUSC 235888, Fadklamia sp. HUSC 263425, Mycobacterium smegmatis UGRA1, Schaalia radingae HUSC 256790, Staphylococcus aureus HUSC 263091 and Staphylococcus epidermidis HUSC. A preferred embodiment of this aspect, the parasites are from the family Trypanosomatidae, more preferably from the genera Trypanosoma and Leishmania and, even more preferably, Trypanosoma brucei, Trypanosoma cruzi and Leishmania major.Another preferred embodiment of this aspect relates to a compound of formula (I), as described in the first aspect of the invention, for use in the treatment and / or prevention of sleeping sickness, Chagas disease, or leishmaniasis. In a preferred embodiment of this aspect, the parasites are from the family Eimeriidae, more preferably from the genus Eimeria, and from the family Sarcocystidae, more preferably from the genus Neospora. Another preferred embodiment of this aspect relates to a compound of formula (I), as described in the first aspect of the invention, for use in the treatment and / or prevention of infections in animals caused by parasites of the families Eimeriidae and Sarcocystidae. Another aspect of the present invention relates to a pharmaceutical composition comprising a compound of formula (I) as described in the first aspect of the invention, together with a pharmaceutically acceptable excipient, adjuvant, and / or vehicle.Another aspect of the invention relates to a method of antibacterial and / or antiparasitic treatment comprising administering to a subject a therapeutically effective amount of a compound of formula (I) as described in the first aspect of the present invention. A final aspect of the present invention relates to the use of a compound of formula (I) as described in the first aspect of the present invention for the preparation of a medicament for use as an antibacterial and / or antiparasitic agent. The compounds of the invention of formula (I) may be in crystalline form as free compounds or as solvates, and it is intended that both forms are within the scope of the present invention. In this sense, the term “solvate,” as used herein, includes pharmaceutically acceptable solvates, i.e., solvates of the compound that can be used in the preparation of a medicament. In one particular embodiment, the solvate is a hydrate.Solvates can be obtained by conventional solvation methods well known to those skilled in the art. Compounds of formula (I) for therapeutic use are prepared in solid form or aqueous suspension in a pharmaceutically acceptable diluent. These preparations can be administered by any appropriate route of administration, for which purpose the preparation will be formulated in the pharmaceutical form suitable for the chosen route of administration. In one particular embodiment, the administration of the compound of formula (I) is by oral, topical, rectal, or parenteral route (including subcutaneous, intraperitoneal, intradermal, intramuscular, intravenous, etc.). The compounds described in the present invention, their pharmaceutically acceptable salts, solvates, and pharmaceutical compositions containing them can be used in conjunction with other drugs to provide combination therapy.These additional drugs may form part of the same pharmaceutical composition or, alternatively, may be provided in the form of a separate composition for administration, whether or not simultaneous with the pharmaceutical composition comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof. Unless otherwise indicated, the compounds of the invention also include compounds differing only in the presence of one or more isotopically enriched atoms. For example, compounds having such a structure, except for the substitution of a hydrogen atom by a deuterium or tritium atom, or the substitution of a carbon atom by a carbon atom enriched in [specific element]. 13 Co 14 C or a nitrogen enriched in 15N, are within the scope of this invention. The present invention encompasses all isomers of compounds of formula (I), that is, all geometric, tautomeric, and optical forms, and mixtures thereof (e.g., racemic mixtures). When there are more than one chiral center in the compounds, the present invention includes within its scope all possible diastereomers, including mixtures thereof. The different isomeric forms can be separated or resolved from one another by conventional methods, or any given isomer can be obtained by conventional synthetic methods or by stereospecific, stereoselective, or asymmetric synthesis. Definitions according to the present invention: The term “alkyl” refers to radicals of saturated, linear, or branched hydrocarbon chains such as, for example, methyl, ethyl, n-propyl, i-propyl, n-butyl, tert-butyl, sec-butyl, n-pentyl, etc. For example,A C1-C5 alkyl group is an alkyl group with 1 to 5 carbon atoms. These alkyl radicals can be optionally substituted at one or more positions by groups such as hydroxyl, amines, amides, cyano, halogens, aryl, etc. The term "aryl" refers to an aromatic carbocyclic chain radical, which can be single-ring or multiple-ring, in the latter case with separate and / or fused rings. A C6-C12 aryl group has 6 to 12 carbon atoms. A non-limiting example of an aryl group is a phenyl group. These radicals can be optionally substituted at one or more positions by groups such as hydroxyl, amines, amides, cyano, halogens, aryl, alkyl, etc. The term “heterocycle” refers to an aromatic (aromatic heterocycle) or aliphatic (aliphatic heterocycle) carbocyclic chain radical in which at least one carbon atom of the ring or rings has been replaced by a heteroatom selected from the group consisting of nitrogen,oxygen and sulfur. The heterocycle can be a monocyclic or bicyclic ring system, which may include fused ring systems. Examples of aromatic heterocycles include, but are not limited to, imidazole, pyrrole, pyridine, pyridazine, pyrazine, quinoline, indole, thiophene, furan, oxazole, and pyrazole. These radicals may be optionally substituted at one or more positions with groups such as hydroxyl, amines, amides, cyano, halogens, aryl, alkyl, etc. Examples of aliphatic heterocycles include, but are not limited to, pyrrolidine, piperidine, piperazine, N-methylpiperazine, and morpholino. These radicals may be optionally substituted in one or more positions with groups such as hydroxyl, amines, amides, cyano, halogens, aryl, alkyls, etc. The term “halogen” refers, in the present invention, to bromine, chlorine,iodine or fluorine. The “glycosyl radical” (substituent R2) in the present invention refers to a radical resulting from the removal of a hydroxyl group (OH) from a natural or synthetic saccharide or sugar, and which is attached to the rest of the molecule through the carbon that has lost the hydroxyl group. The terms monoglycosyl, diglycosyl, and triglycosyl refer to glycosyl radicals resulting from a monosaccharide, a disaccharide, or a trisaccharide, respectively. Thus, for example, a glycosyl radical is a radical resulting from the removal of an OH group from glucose, and this radical is attached to the rest of the molecule through the carbon that has lost the OH group. Or, for example, a 6-deoxyglucosyl radical is a radical resulting from the removal of an OH group from 6-deoxyglucose, and this radical is attached to the rest of the molecule through the carbon that has lost the OH group. In a preferred embodiment of the invention,The glycosyl radical is attached to the rest of the molecule by the anomeric carbon that has lost the OH. Glycosyl radicals include those derived from deoxy sugars (one or more carbons in the saccharide molecule lack a hydroxyl group attached to the carbon, regardless of which one it will later lose to join the rest of the molecule), alkylated sugars (one or more carbons in the saccharide molecule replace the hydroxyl group attached to the carbon with an O-alkyl group, where the alkyl is preferably C1-C4), thiosugars (sugars that have replaced the ring oxygen of the saccharide with a sulfur atom), selenosugars (sugars that have replaced the ring oxygen of the saccharide with a selenium atom), aminosugars (sugars that have replaced at least one of the hydroxyls of the saccharide with an amino group), iminosugars (sugars that have replaced the ring oxygen of the saccharide with a nitrogen atom),phosphosugar (a sugar in which at least one of the hydroxyl groups of the saccharide is esterified with a phosphate group), carbasugar (a sugar in which the ring oxygen of the saccharide has been replaced by a carbon atom), fluorosugar (a sugar in which at least one of the hydroxyl groups of a saccharide has been replaced by a fluorine atom), or any combination thereof. In a preferred embodiment, the glycosyl radical is attached to the rest of the molecule by the anomeric carbon. The term “treatment or prevention,” as used herein, unless otherwise stated, means to reverse, alleviate, inhibit the progression of, or prevent the disorder or condition to which it is applied in such terms, or one or more symptoms of such disorder or condition. The term “excipients, adjuvants, and / or vehicles” refers to molecular entities or substances with which the active ingredient is administered. Such excipients, adjuvants, or pharmaceutical vehicles may be sterile liquids, such as waters and oils,including those of petroleum or animal, vegetable, or synthetic origin, such as peanut oil, soybean oil, mineral oil, sesame oil, and the like, excipients, disintegrants, wetting agents, or diluents. Suitable pharmaceutical excipients and vehicles are described in “Remington’s Pharmaceutical Sciences” by E.W. Martin. The term “therapeutically effective amount” means the amount of a compound necessary for it to be effective in treating or preventing the disease, disorder, or condition. Throughout the description and claims, the word “comprises” and its variants are not intended to exclude other technical features, additives, components, or steps. For those skilled in the art, other objects, advantages, and features of the invention will become apparent partly from the description and partly from the practice of the invention. The following examples are provided for illustrative purposes.and are not intended to be limiting to the present invention. EXAMPLES Example 1. Synthesis and characterization of compounds within the scope of the invention. The synthesis of the carbohydrate-pyrvinium conjugates linked at the phenyl position is a modification of the method described for the synthesis of pyrvinium (1) in Gaikwad et al. (Bioorg. Med. Chem. Lett., 30 (2020) 127037). 1-(4-Ethynylphenyl)-2,5-dimethyl-1H-pyrrole (Paal-Knorr Reaction), To a stirred solution of 4-ethynylaniline (Sigma-Aldrich, CAS: 14235-81-5) (1.2 eq., 5 g, 42.68 mmol) were added 2,5-hexadione (1 eq., 4.288 mL, 35.56 mmol) and Amberlite IR120 (2 g). The reaction was maintained at room temperature, without solvent, for 24 hours. Once the reaction was complete, the mixture was diluted with diethyl ether and filtered to recover the catalyst. The organic phase was washed with a saturated sodium bicarbonate and brine solution, dried with Na₂SO₄, and concentrated under vacuum. The organic phase was purified by silica-gel column chromatography (0.04-0.063 µm) using a mobile phase of 100% hexane to hexane / ethyl acetate (30:1) to obtain a pure white product (1.18 g, 17%). 1 H NMR (400 MHz, CDCl3) δ 7.67 – 7.59 (m, 2H), 7.26 – 7.18 (m, 2H), 5.96 (s, 2H), 3.18 (s, 1H), 2.09 (s, 6H); 13C NMR (101 MHz, CDCl3) δ 139.37, 132.93, 128.69, 128.24, 121.57, 106.23, 82.85, 78.29, 77.43, 77.11, 76.79, 13.05; ESI-HRMS for C 14 H 13 N (MH + ) calculated mass: 196.1048; found: 196.1121. 1-(4-ethynylphenyl)-2,5-dimethyl-1H-pyrrole-3-carbaldehyde (Vilsmeier-Haack reaction) To a stirred solution of 1-(4-ethynylphenyl)-2,5-dimethyl-1H-pyrrole (1 eq., 200 mg, 1.025 mmol) in anhydrous DMF (1 eq., 75 mg, 1.025 mmol) and anhydrous toluene (1.75 mL), POCl3 (1 eq., 157 mg, 1.025 mmol) was added dropwise. The solution was heated to 110°C for 6 hours. The mixture was cooled to room temperature. A saturated solution of NaOCl (10 mL) was added, and the mixture was stirred vigorously for 20 minutes. 50 mL of dichloromethane and 430 mg of solid K2CO3 were added, and the mixture was stirred. The organic phase was washed with NaHCO3 and brine, and the organic phase was dried with anhydrous Na2SO4 and evaporated under vacuum. The residue was purified by silica gel column chromatography using a mobile phase of hexane / ethyl acetate (4:1) to hexane / ethyl acetate (2:1) to obtain a solid product (200 mg, 88%). 1 H NMR (400 MHz, CDCl3) δ 9.89 (s, 1H), 7.70 – 7.61 (m, 2H), 7.27 – 7.15 (m, 2H), 6.41 (q, J = 1.1 Hz, 1H), 3.21 (s, 1H), 2.30 (s, 3H), 2.01 (d, J = 1.1 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ 139.37, 132.93, 128.69, 128.24, 128.22, 121.57, 106.23, 106.21, 82.85, 78.29, 77.43, 77.11. 76.79, 30.95, ESI-HRMS for C 15 H 13 NO (MH + ) calculated mass: 224.0997; found: 224.1118. N,N-2-trimethylquinoline-6-amine 4-(N,N-Dimethylamino)aniline (Thermo Fisher Scientific, CAS: 99-98-9) (1 eq., 5 g, 36.7 mmol) was dissolved in 66 mL of HCl solution, and after the addition of crotonaldehyde (2 eq., 6 mL, 73.5 mmol), the mixture was stirred for 1 hour at room temperature. Toluene (35 mL) was then added, and the reaction was heated and refluxed for 20 hours. The mixture was cooled to room temperature and neutralized by adding a saturated NaOH solution. Extraction was performed with dichloromethane, and the organic phase was washed twice with water and brine, then dried with anhydrous MgSO4, filtered, and concentrated under vacuum. The crude was purified by silica gel column chromatography (0.04-0.063 µm) using a mobile phase of 100% CH2Cl2a CH2Cl2 / MeOH (3:1) to obtain the pure product (5.51 g, 81%). 1H NMR (400 MHz, MeOD) δ 7.94 (d, J = 8.5 Hz, 1H), 7.77 (d, J = 9.3 Hz, 1H), 7.37 (dd, J = 9.3, 2.9 Hz, 1H), 7.19 (d, J = 8.4 Hz, 1H), 6.84 (d, J = 2.9 Hz, 1H), 3.00(s, 6H), 2.60(s, 3H); 13 C NMR (101 MHz, MeOD) δ 154.08, 148.53, 140.82, 135.30, 128.10, 127.19, 121.92, 119.50, 105.18, 48.27, 48.06, 47.84, 47.63,000; 47.42, 47.20, 46.99, 39.54, 22.74; ESI-HRMS for C 12 H 14 N2(MH + ) calculated mass: 187.1157; found: 187.1255. 6-(Dimethylamino)-1,2-dimethylquinolin-1-io iodide N,N-2-Trimethylquinolin-6-amine (1 eq., 3.11 g, 16.71 mmol) was dissolved in 60 mL of anhydrous DMF, and methyl iodide (5 eq., 5.2 mL, 83.55 mmol) was added dropwise. The reaction was maintained under argon atmosphere, at reflux (105 °C), for 23 hours. The mixture was cooled to room temperature, and the solvent was removed in vacuo. The solid was washed three times with ethyl ether and filtered. The crude product was then purified by silica gel column chromatography (0.04–0.063 µm) using a 100% CH₂Cl₂a CH₂Cl₂ / MeOH mobile phase (9:1) to obtain an orange solid product (2.47 g, 45%). 1 H NMR (400 MHz, DMSO) δ 8.73 (d, J = 8.6 Hz, 1H), 8.35 (dd, J = 9.8, 0.9 Hz, 1H), 7.86 (d, J = 8.7 Hz, 1H), 7.76 (dd, J = 9.8, 3.0 Hz, 1H), 7.27 (d, J = 3.0 Hz, 1H), 4.36 (s, 3H), 3.12 (s, 6H), 2.95 (s, 3H). 13C NMR (101 MHz, DMSO) δ 154.96, 149.63, 143.11, 132.41, 130.45, 125.27, 123.44, 119.97, 106.04, 40.64, 40.43, 40.30, 40.27, 40.22, 40.06, 40.01, 39.81, 39.60, 39.39, 22.63. ESI-HRMS for C 13 H 17 N2(M) calculated mass: 201.1386; found: 201.1394. To a solution of 6-(dimethylamino)-1,2-dimethylquinolin-1-iodide (1 eq., 1.618 g, 4.932 mmol) and 1-(4-ethynylphenyl)-2,5-dimethyl-1H-pyrrole-3-carbaldehyde (2 eq., 1.772 g, 7.942 mmol) in methanol (120 mL), piperidine (23-24 drops) was added and the reaction mixture was heated and held under reflux for 24 hours. The reaction mixture was cooled to room temperature and purified by silica gel column chromatography (0.04-0.063 µm) using a mobile phase of 100% CH2Cl2a CH2Cl2 / MeOH (40:1) to obtain a dark red product (1.153 g, 44%). 1H NMR (400 MHz, DMSO) δ 8.53 (d, J = 9.2 Hz, 1H), 8.44 (d, J = 9.4 Hz, 1H), 8.23 ​​(d, J = 9.7 Hz, 1H), 8.07 (d, J = 15.1 Hz, 1H), 7.69 (d, J = 1.9). Hz, 1H), 7.68 – 7.66 (m, 1H), 7.62 (ddd, J = 9.8, 6.8, 2.6 Hz, 1H), 7.41 (d, J = 1.9 Hz, 1H), 7.39 (s, 1H), 7.23 (dd, J = 9.1, 6.0 Hz, 2H), 6.75 (d, J = 1.3 Hz, 1H), 4.37 (s, 3H), 3.11 (s, 7H), 2.25 (s, 3H), 2.03 (d, J = 0.9 Hz, 3H). 13 C NMR (101 MHz, DMSO) δ 151.89, 149.25, 140.32, 139.12, 137.70, 136.22, 133.39; 120.57, 120.00, 119.77, 112.40, 106.85, 105.51, 83.02, 82.77, 55.42, 13.14, 11.32. ESI-HRMS for C 28 H 28 N3(M) calculated mass: 406.2361; found: 406.2348. Trifluoroacetate of 2-((E)-2-(2,5-dimethyl-1-(4-(1-glucopyranosyl)-1H-1,2,3-triazol-4-yl)phenyl)-1H-pyrrol-3-yl)vinyl)-6-(dimethylamino)-1-methylquinoline-1-io (glc-PYR, 2). To a solution of (E)-6-(dimethylamino)-2-(2-(1-(4-ethynylphenyl)-2,5-dimethyl-1H-pyrrol-3-yl)vinyl)-1-methylquinolin-1-ium iodide (1 eq, 40 mg, 0.075 mmol) in THF / H2O (1:1, 3 mL) CuSO4^5H2O was added. (0.1 eq, 1.86 mg, 0.007 mmol), sodium ascorbate (0.5 eq, 7.1 mg, 0.038 mmol), THPTA (0.1 eq, 3.2 mg, 0.008 mmol) and 1-azidoglucose (Sigma-Aldrich, CAS: 20379-59-3) (2 eq; 30 mg; 0.15 mmol). The reaction mixture was stirred at 100 °C in a microwave oven (150 W) for 45 min. The mixture was cooled, dried under vacuum, and purified using a Teledyne Isco 15.5 g HP C18 automated column (VC 13.5 mL – 30 mL / min). The solvents used for purification were: A) 0.5% trifluoroacetic acid in Milli-Q water and B) 0.5% trifluoroacetic acid in acetonitrile.In the method used, a flow rate of 30 mL / min was maintained, starting with 90% aqueous solvent for 1 minute, which was gradually reduced to 20% over 13 minutes and held for 3 minutes. After this 3 minutes, the mixture was returned to an initial isocratic state (λ detection: 214 and 254 nm). A red solid (12 mg, 22%) was obtained. 1 H NMR (400 MHz, Methanol-d4) δ 8.71 (s, 1H), 8.42 (d, J = 9.2 Hz, 1H), 8.18 (dd, J = 17.7, 9.5 Hz, 2H), 8.07 (d, J = 8.4 Hz, 2H), 7.62 (dd, J = 9.7, 2.9 Hz, 1H), 7.38 (d, J = 8.4 Hz, 2H), 7.23 – 7.12 (m, 3H), 6.61 (s, 1H), 5.71 (d, J = 9.2 Hz, 1H), 4.39 (s, 3H), 4.05 – 3.91 (m, 3H), 3.78 (dd, J = 12.2, 5.4Hz, 2H), 3.67 – 3.53 (m, 4H), 3.16 (s, 6H), 2.29 (s, 3H), 2.11 (s, 3H). 13C NMR (126 MHz, MeOD) δ 153.64, 150.78, 141.65, 140.29, 133.59, 133.06, 132.42, 130.66, 129.82, 127.89, 12.8, 12.12. 120.99, 120.72, 120.02, 112.24, 107.64, 105.50, 89.82, 81.25, 78.51, 74.13, 70.94, 62.40, 40.29, 38.8, 1.2.19, ESI-HRMS C 34 H 39 N6O5 + (M) calculated mass: 611.2982; found: 611.2961. Trifluoroacetate of 2-((E)-2-(2,5-dimethyl-1-(4-(1-(6-deoxyglucopyranosyl)-1H-1,2,3- triazol-4-yl)phenyl)-1H-pyrrole-3-yl)vinyl)-6-(dimethylamino)-1-methylquinolin-1-P 3). To a solution of (E)-6-(dimethylamino)-2-(2-(1-(4-ethynylphenyl)-2,5-dimethyl-1H-pyrrole-3-yl)vinyl)-1-methylquinolin-1-iodide (1 eq., 100 mg, 0.187 mmol) in THF / H2O (1:1, 12 mL) were added CuSO4^5H2O (0.1 eq., 4.6 mg, 0.187 mmol), sodium ascorbate (0.5 eq., 18.5 mg, 0.093 mmol), THPTA (0.1 eq., 8.1 mg, 0.0187 mmol) and 1-azido-6-deoxy-glucose (Arévalo-Ruiz et al., Chem. Eur. J. 2017, 23, 2157) (2 eq., 77 mg, 0.375 mmol). The reaction mixture was kept stirring at 100 °C in a microwave (150 W) for 45 min. The mixture was cooled, dried under vacuum, and then purified by C18 column flash chromatography using a mobile phase of H2O (+0.1% TFA) / CH3CN (+0.1% TFA) 90:10 to H2O (+0.1% TFA) / CH3CN (+0.1% TFA) 20:80 to obtain a dark red solid product (32 mg, 24%). 1H RMN (400 MHz, DMSO) δ 8.93 (s, 1H), 8.51 (d, J = 9.3 Hz, 1H), 8.43 (d, J = 9.4 Hz, 1H), 8.22 (d, J = 9.8 Hz, 1H), 8.11 – 8.05 (m, 3H), 7.60 (dd, J = 9.8, 3.0 Hz, 1H), 7.45 (d, J = 8.4 Hz, 2H), 7.25 – 7.20 (m, 2H), 6.74 (s, 1H), 5.61 (d, J = 9.3 Hz, 1H), 4.36 (s, 3H), 3.84 (t, J = 9.1 Hz, 2H), 3.10 (s, 6H), 3.05 (d, J = 9.1 Hz, 2H), 2.28 (s, 3H), 2.05 (s, 3H), 1.22 (d, J = 6.1 Hz, 3H). 13 C RMN (101 MHz, DMSO) δ 158.73, 158.39, 152.03, 149.32, 145.94, 140.40, 139.30, 136.87, 136.46, 131.96, 131.78, 131.33, 129.26, 128.95, 126.72, 121.92, 121.50, 120.58, 119.97, 119.62, 112.21, 106.86, 105.26, 88.16, 77.02, 75.36, 75.21, 72.92, 40.57, 40.52, 40.36, 40.31, 40.27, 40.15, 40.10, 39.94, 39.89, 39.69, 39.48, 39.27, 38.90, 18.27, 13.13, 11.30. ESI-HRMS para C 34 H 39 N6O4 +(M) masa calculada: 595.3033; encontrada: 595.3044. Trifluoroacetato de 2-((E)-2-(2,5-dimetil-1-(4-(1-(6-desoxi-6-fluoroglucopyranosil)-1H- 1,2,3-triazol-4-il)fenil)-1H-pirrol-3-il)vinil)-6-(dimetilamino)-1-metilquinolin-1-io (6Fglc- To a solution of (E)-6-(dimethylamino)-2-(2-(1-(4-ethynylphenyl)-2,5-dimethyl-1H-pyrrole-3-yl)vinyl)-1-methylquinolin-1-ium iodide (1 eq., 59.71 mg, 0.112 mmol) in THF / H2O (1:1, 8 mL) were added CuSO4^5H2O (0.1 eq., 2.79 mg, 0.0112 mmol), sodium ascorbate (0.5 eq., 11.09 mg, 0.056 mmol), THPTA (0.1 eq., 4.86 mg, 0.0112 mmol) and 1-azido-6-deoxy-6-fluoroglucose (Maschauer et al., Mol Pharm.2014;11(2):505-515) (2 eq., 46.3 mg, 0.224 mmol). The reaction mixture was kept stirring at 100 °C in a microwave (150 W) for 45 min. The mixture was cooled, dried under vacuum, and then purified by C18 column flash chromatography using a mobile phase of H2O (+0.1% TFA) / CH3CN (+0.1% TFA) 90:10 to H2O (+0.1% TFA) / CH3CN (+0.1% TFA) 20:80 to obtain a dark red solid product (29.8 mg, 37%). 1H RMN (400 MHz, MeOD) δ 8.71 (s, 1H), 8.44 (d, J = 9.2 Hz, 1H), 8.22 (d, J = 9.2 Hz, 1H), 8.17 (d, J = 9.7 Hz, 1H), 8.12 – 8.07 (m, 2H), 8.03 (d, J = 15.1 Hz, 1H), 7.64 (dd, J = 9.8, 3.0 Hz, 1H), 7.43 – 7.37 (m, 2H), 7.20 (d, J = 15.2 Hz, 1H), 7.16 (d, J = 3.0 Hz, 1H), 6.62 (d, J = 1.2 Hz, 1H), 5.74 (d, J = 9.2 Hz, 1H), 4.77 – 4.74 (m, 1H), 4.65 – 4.62 (m, 1H), 4.41 (s, 3H), 4.02 (t, J = 9.0 Hz, 1H), 3.63 (dd, J = 12.4, 9.0 Hz, 2H), 3.17 (s, 6H), 2.30 (s, 3H), 2.11 (d, J = 1.0 Hz, 3H). 13 C RMN (126 MHz, MeOD) δ 152.33, 149.42, 146.44, 140.29, 138.94, 137.30, 136.28, 132.18, 131.70, 131.00, 129.29, 128.41, 126.54, 121.45, 120.53, 119.63, 119.31, 118.62, 110.88, 106.26, 104.08, 88.25, 82.29, 80.92, 78.12, 77.98, 77.01, 72.48, 68.51, 48.11, 47.94, 47.77, 47.60, 47.43, 47.26, 47.09, 38.90, 37.48, 11.51, 11.47, 9.67. ESI-HRMS for C 34 H 38 FN6O4 +(M) masa calculada: 613.2939; encontrada: 613.2955. Trifluoroacetato de 2-((E)-2-(2,5-dimetil-1-(4-(1-fucosil)-1H-1,2,3-triazol-4-il)fenil)-1H- pirrol-3-il)vinil)-6-(dimetilamino)-1-metilquinolin-1-io (fuc-PYR, 5). To a solution of (E)-6-(dimethylamino)-2-(2-(1-(4-ethynylphenyl)-2,5-dimethyl-1H-pyrrole-3-yl)vinyl)-1-methylquinolin-1-iodide (1 eq; 40 mg; 0.075 mmol) in THF / H2O (1:1, 3 mL) CuSO4^5H2O (0.1 eq; 1.86; 0.008 mmol), sodium ascorbate (0.5 eq; 7.42 mg; 0.15 mmol), THPTA (0.1 eq; 3.25 mg; 0.008 mmol) and 1-azidofucose (Synthose, CAS: 66347-26-0) (2 eq; 28 mg; 0.15 mmol) was added. The reaction mixture was stirred at 100 °C in a microwave oven (150 W) for 45 min. The mixture was cooled, dried under vacuum, and purified using a Teledyne Isco 15.5 g HP C18 automated column (VC 13.5 mL – 30 mL / min). The solvents used for purification were A) 0.5% trifluoroacetic acid in Milli-Q water, B) 0.5% trifluoroacetic acid in acetonitrile.In the method used, a flow rate of 30 mL / min was maintained, starting with 90% aqueous solvent for 1 minute, which was gradually reduced to 20% over 13 minutes and held for 3 minutes. After this time, the mixture was returned directly to an isocratic mixture (λ detection: 214 and 254 nm). A red solid (50 mg, 54%) was obtained. 1 H NMR (400 MHz, Methanol-d4) δ 8.69 (s, 1H), 8.38 (d, J = 9.0 Hz, 1H), 8.19 – 8.11 (m, 2H), 8.07 – 8.00 (m, 2H), 7.94 (d, J = 15.0 Hz, 1H), 7.57 (d, J = 9.5 Hz, 1H), 7.34 (d, J = 8.0 Hz, 2H), 7.10 (d, J = 14.3 Hz, 2H), 6.57 (s, 1H), 5.63 (dd, J = 9.2, 3.7 Hz, 1H), 4.35 (d, J = 6.9 Hz, 3H), 4.18 (t, J = 9.3Hz, 1H), 4.02 (q, J = 6.2, 5.8 Hz, 1H), 3.81 (d, J = 3.0 Hz, 1H), 3.75 (dd, J = 9.4, 3.2 Hz, 1H), 3.12 (s, 6H), 2.25 (s, 3H), 2.08 (s, 3H), 1.33 (t, J = 6.5Hz, 3H). 13C NMR (101 MHz, MeOD) δ 141.61, 140.22, 137.71, 133.62, 129.80, 127.87, 122.77, 121.45, 120.94, 120.71, 10.1, 2.1, 1.5. 107.63, 105.51, 90.39, 75.48, 75.43, 73.03, 71.35, 40.28, 38.86, 16.83, 12.94, 11.10. ESI-HRMS for C 34 H 39 N6O4 + (M) calculated mass: 595.3033; found: 595.3044. Trifluoroacetate of 2-((E)-2-(2,5-dimethyl-1-(4-(1-(xylopyranosyl)-1H-1,2,3-triazol-4-yl)phenyl)- 1H-pyrrole-3-yl)vinyl)-6-(dimethylamino)-1-methylquinoline-1-Pio (Xyl-YR,6). To a solution of (E)-6-(dimethylamino)-2-(2-(1-(4-ethynylphenyl)-2,5-dimethyl-1H-pyrrole-3-yl)vinyl)-1-methylquinolin-1-ium iodide (1 eq., 69.3 mg, 0.13 mmol) in THF / H2O (1:1, 12 mL) were added CuSO4^5H2O (0.1 eq., 3.24 mg, 0.013 mmol), sodium ascorbate (0.5 eq., 12.87 mg, 0.065 mmol), THPTA (0.1 eq., 5.64 mg, 0.013 mmol) and β-D-xylopyranosyl azide (Apollo Scientific, CAS: 51368-20-8) (2 eq., 45.8 mg, 0.261 mmol). The reaction mixture was kept stirring at 100 °C in a microwave (150 W) for 45 min. The mixture was cooled, dried under vacuum, and then purified by C18 column flash chromatography using a mobile phase of H2O (+0.1% TFA) / CH3CN (+0.1% TFA) 90:10 to H2O (+0.1% TFA) / CH3CN (+0.1% TFA) 20:80 to obtain a dark red solid product (26.6 mg, 30%). 1H RMN (400 MHz, DMSO) δ 8.97 (s, 1H), 8.53 (d, J = 9.2 Hz, 1H), 8.46 (d, J = 9.2 Hz, 1H), 8.23 (d, J = 9.7 Hz, 1H), 8.14 – 8.03 (m, 3H), 7.61 (dd, J = 9.7, 2.9 Hz, 1H), 7.47 (d, J = 8.0 Hz, 2H), 7.28 – 7.21 (m, 2H), 6.75 (s, 1H), 5.57 (d, J = 9.2 Hz, 1H), 4.37 (s, 3H), 3.90 (dd, J = 10.7, 4.9 Hz, 1H), 3.82 (t, J = 9.0 Hz, 1H), 3.57 – 3.37 (m, 4H), 3.11 (s, 6H), 2.29 (s, 3H), 2.06 (s, 3H). 13 C RMN (126 MHz, DMSO) δ 158.31, 152.04, 149.31, 145.93, 140.36, 139.36, 136.87, 136.51, 131.94, 131.80, 131.37, 129.26, 128.98, 126.67, 121.89, 121.48, 120.60, 120.02, 119.66, 112.23, 106.90, 105.29, 88.85, 77.42, 72.72, 69.67, 68.87, 40.58, 40.49, 40.42, 40.32, 40.29, 40.25, 40.16, 40.08, 39.99, 39.91, 39.82, 39.66, 39.49, 38.92, 13.17, 11.32. ESI-HRMS para C 33 H 37 N6O4 +(M) calculated mass: 581.2876; found: 581.2888. 2-((E)-2-(2,5-dimethyl-1-(4-(1-(maltopyranosyl)-1H-1,2,3-triazol-4-yl)phenyl)-1H-pyrrol-3-yl)vinyl)-6-(dimethylamino)-1-methylquinolin-1-ium trifluoroacetate (malt-PYR, 8). To a solution of (E)-6-(dimethylamino)-2-(2-(1-(4-ethynylphenyl)-2,5-dimethyl-1H-pyrrole-3-yl)vinyl)-1-methylquinolin-1-ium iodide (1 eq., 42.5 mg, 0.079 mmol) in THF / H2O (1:1, 12 mL) were added CuSO4^5H2O (0.1 eq., 1.99 mg, 0.0079 mmol), sodium ascorbate (0.5 eq., 7.9 mg, 0.0399 mmol), THPTA (0.1 eq., 3.47 mg, 0.0079 mmol) and 1-azidomaltose (Synthose, CAS: 51970-30-0) (2 eq., 42.4 mg, 0.159 mmol). The reaction mixture was kept stirring at 100 °C in a microwave (150 W) for 30 min. The mixture was cooled, dried under vacuum, and then purified by C18 column flash chromatography using a mobile phase of H2O (+0.1% TFA) / CH3CN (+0.1% TFA) 90:10 to H2O (+0.1% TFA) / CH3CN (+0.1% TFA) 20:80 to obtain a dark red solid product (44 mg, 62%).1 H RMN (400 MHz, DMSO) δ 8.99 (s, 1H), 8.53 (d, J = 9.2 Hz, 1H), 8.47 (d, J = 9.3 Hz, 1H), 8.24 (d, J = 9.7 Hz, 1H), 8.13 (s, 2H), 8.08 (d, J = 8.3 Hz, 2H), 7.62 (dd, J = 9.8, 3.0 Hz, 1H), 7.48 (d, J = 8.2 Hz, 2H), 7.29 – 7.21 (m, 2H), 6.76 (s, 1H), 5.71 (d, J = 9.1 Hz, 1H), 5.12 (d, J = 3.9 Hz, 1H), 4.38 (s, 3H), 3.92 (t, J = 9.1 Hz, 2H), 3.79 (d, J = 3.9 Hz, 1H), 3.75 (d, J = 9.2 Hz, 2H), 3.68 (s, 1H), 3.64 (d, J = 5.2 Hz, 1H), 3.58 – 3.53 (m, 2H), 3.52 (d, J = 6.2 Hz, 1H), 3.47 (d, J = 6.7 Hz, 1H), 3.43 (d, J = 9.1 Hz, 1H), 3.30 (dd, J = 9.7, 3.7 Hz, 1H), 2.29 (s, 3H), 2.07 (s, 3H). 13C NMR (126 MHz, DMSO) δ 149.95, 147.28, 143.96, 138.42, 137.13, 134.89, 134.34, 129.96, 129.69, 124.73, 119.92, 119.59, 118.51, 117.84, 117.49, 116.58, 110.15, 104.73, 103.15, 99.25, 85.82, 77.3, 7.5, 7.5, 7.6. 71.92, 71.62, 70.76, 70.21, 68.27, 59.23, 58.65, 38.21, 38.12, 38.04, 37.96, 37.87, 37.79, 37.71, 37.2, 37.4, 37.4. 37.45, 37.29, 37.12, 36.80, 29.08, 11.04, 9.21. ESI-HRMS for C 40 H 49 N6O 10 + (M) calculated mass: 773.3510; found: 773.3532. Trifluoroacetate of 2-((E)-2-(2,5-dimethyl-1-(4-(1-(glucopyranosyl-ethyl)-1H-1,2,3-triazol-4- yl)phenyl)-1H-pyrrole-3-yl)vinyl)-6-(dimethylamino)-1-methylquino (P-Y 9). To a solution of (E)-6-(dimethylamino)-2-(2-(1-(4-ethynylphenyl)-2,5-dimethyl-1H-pyrrole-3-yl)vinyl)-1-methylquinolin-1-ium iodine (1 eq., 45 mg, 0.085 mmol) in THF / H2O (1:1, 5 mL) were added CuSO4^5H2O (0.1 eq., 2.1 mg, 0.0085 mmol), sodium ascorbate (0.5 eq., 8.4 mg, 0.042 mmol), THPTA (0.1 eq., 4.5 mg, 0.0085 mmol) and 2-azidoethyl glucopyranoside (Sigma-Aldrich, CAS: 165331-08-8) (2 eq., 36 mg, 0.1448 mmol). The reaction mixture was kept stirring at 100 °C in a microwave (150 W) for 40 min. The mixture was cooled, dried under vacuum, and then purified by C18 column flash chromatography using a mobile phase of H2O (+0.1% TFA) / CH3CN (+0.1% TFA) 80:20 to H2O (+0.1% TFA) / CH3CN (+0.1% TFA) 20:80 to obtain a dark red solid product (10 mg, 15%). 1H RMN (400 MHz, DMSO) δ 8.76 (s, 1H), 8.54 – 8.41 (m, 2H), 8.23 (d, J = 9.8 Hz, 1H), 8.10 (d, J = 15.1 Hz, 1H), 8.07 – 8.00 (m, 2H), 7.61 (dd, J = 9.8, 3.0 Hz, 1H), 7.45 (d, J = 2.1 Hz, 1H), 7.43 (d, J = 2.1 Hz, 1H), 7.28 – 7.20 (m, 2H), 6.78 – 6.70 (m, 1H), 4.73 – 4.64 (m, 2H), 4.64 – 4.56 (m, 1H), 4.37 (s, 3H), 4.28 (d, J = 7.7 Hz, 1H), 4.17 (ddd, J = 11.4, 5.9, 3.8 Hz, 2H), 3.95 (ddd, J = 11.1, 7.0, 3.9 Hz, 2H), 3.73 (d, J = 2.1 Hz, 1H), 3.70 (d, J = 2.0 Hz, 1H), 3.11 (s, 6H), 2.28 (s, 3H), 2.06 (s, 3H). 13 C RMN (101 MHz, DMSO) δ 152.05, 149.33, 145.74, 140.39, 139.35, 136.69, 136.50, 131.97, 131.80, 131.66, 129.26, 128.91, 126.63, 123.40, 121.91, 120.59, 119.99, 119.63, 112.22, 106.88, 105.25, 103.27, 77.44, 77.04, 73.83, 70.53, 67.78, 61.57, 56.50, 50.32, 40.62, 40.57, 40.41, 40.36, 40.28, 40.21, 40.16, 40.00, 39.95, 39.74, 39.53, 39.32, 38.92, 19.00, 13.15, 11.32. ESI-HRMS para C 36 H 43 N6O6 +(M) calculated mass: 655.3239; found: 655.3243. 2-((E)-2-(2,5-dimethyl-1-(4-(1-(2-ethyl-galactopyranosyl)-1H-1,2,3-triazol- 4-yl)phenyl)-1H-pyrrol-3-yl)vinyl)-6-(dimethylamino)-1-methylquinolin-1-ium trifluoroacetate (gal-C2-PYR, 10). To a solution of (E)-6-(dimethylamino)-2-(2-(1-(4-ethynylphenyl)-2,5-dimethyl-1H-pyrrol-3-yl)vinyl)-1-methylquinolin-1-ium iodine (1 eq., 53 mg; 0.1 mmol) in THF / H2O (1:1, 3 mL) was added CuSO4^5H2O (0.1 eq; 2.49 mg; 0.01 mmol), sodium ascorbate (0.5 eq; 9.9 mg; 0.05 mmol), THPTA (0.1 eq; 4.34 mg; 0.001 mmol) and 2-azidoethyl galactopyranoside (Synthose, CAS: 151651-54-6) (2eq; 50 mg; 0.2 mmol). The reaction mixture was kept stirring at 100 °C in a microwave (150 W) for 40 min. The mixture was cooled, dried under vacuum, and purified using a Teledyne Isco 15.5g HP C18 automated column (VC 13.5 mL – 30 mL / min).The solvents used for purification were A) 0.5% trifluoroacetic acid in Milli-Q water, and B) 0.5% trifluoroacetic acid in acetonitrile. The method employed maintained a flow rate of 30 mL / min, starting with 90% aqueous solvent for 1 minute, which was gradually reduced to 20% over 13 minutes. The solvent concentration was maintained at 20% for 3 minutes, after which the solvent was returned directly to an isocratic mixture (detection wavelength: 214 and 254 nm). A red solid (40.4 mg, 61%) was obtained. 1 H NMR (400 MHz, Methanol-d4) δ 8.60 (s, 1H), 8.37 (d, J = 9.1 Hz, 1H), 8.12 (dd, J = 12.9, 9.7 Hz, 3H), 8.02 (d, J = 8.1 Hz, 3H), 7.93 (d, J = 15.0 Hz, 1H), 7.61 – 7.52 (m, 2H), 7.32 (d, J = 8.2 Hz, 3H), 7.08 (d, J = 15.0 Hz, 3H), 6.56 (s, 1H), 4.73 (s, 3H), 4.33 (d, J = 4.6 Hz, 9H), 4.11 – 4.04 (m, 2H), 3.76 (tt, J = 11.5, 6.8 Hz, 4H), 3.61 – 3.54 (m, 3H), 3.49 (dd, J = 9.7, 3.2 Hz, 2H), 2.24 (s, 3H), 2.07 (s, 3H). 13C NMR (101 MHz, MeOD) δ 150.69; 112.10, 107.60, 105.49, 105.31, 76.90, 74.91, 72.44, 70.33, 69.19, 62.58, 51.88, 48.36, 40.27, 38.84, 12.95, 11.10. ESI-HRMS for C 36 H 43 N6O6 +(M) calculated mass: 655.3244; found: 655.3235. 2-((E)-2-(2,5-dimethyl-1-(4-(1-(2,6-deoxy-^^^^-glucopyranosyl-O-ethyl)- 1H-1,2,3-triazol-4-yl)phenyl)-1H-pyrrol-3-yl)vinyl)-6-(dimethylamino)-1-methylquinolin-1-io (2,6-) trifluoroacetate ddglc-PYR, 11). To a solution of (E)-6-(dimethylamino)-2-(2-(1-(4-ethynylphenyl)-2,5-dimethyl-1H-pyrrol-3-yl)vinyl)-1-methylquinolin-1-ium iodide (1 eq., 47.23 mg, 0.088 mmol) in THF / H2O (1:1, 8 mL) was added CuSO4^5H2O (0.1 eq., 2.19 mg, 0.0088 mmol), sodium ascorbate (0.5 eq., 8.78 mg, 0.044 mmol), THPTA (0.1 eq., 3.8 mg, 0.0088 mmol) and 2-azidoethyl 2,6-dideoxy- ^^^-glucopyranoside (Bennet and Galan., Chem Rev.2018;118(17):7931-7985) (2 eq., 38.5 mg, 0.177 mmol). The reaction mixture was kept stirring at 100 °C in a microwave (150 W) for 45 min. The mixture was cooled, dried under vacuum, and then purified by C18 column flash chromatography using a mobile phase of H2O (+0.1% TFA) / CH3CN (+0.1% TFA) 90:10 to H2O (+0.1% TFA) / CH3CN (+0.1% TFA) 20:80 para obtener un producto sólido rojo oscuro (27.4 mg, 42 %). 1 H RMN (400 MHz, MeOD) δ 8.48 (d, J = 6.8 Hz, 1H), 8.43 (d, J = 9.2 Hz, 1H), 8.22 (d, J = 9.3 Hz, 1H), 8.17 (d, J = 9.7 Hz, 1H), 8.08 – 8.04 (m, 2H), 8.04 – 7.99 (m, 1H), 7.63 (dd, J = 9.7, 3.0 Hz, 1H), 7.41 – 7.36 (m, 2H), 7.19 (d, J = 15.1 Hz, 1H), 7.15 (d, J = 3.0 Hz, 1H), 6.61 (d, J = 1.2 Hz, 1H), 4.86 (d, J = 3.5 Hz, 2H), 4.71 (td, J = 6.2, 4.0 Hz, 2H), 4.40 (s, 3H), 4.12 (ddd, J = 10.8, 6.7, 3.9 Hz, 1H), 4.08 – 3.98 (m, 1H), 3.96 – 3.87 (m, 1H), 3.73 (ddd, J = 11.7, 9.0, 5.1 Hz, 1H), 3.17 (s, 6H), 2.96 – 2.88 (m, 1H), 2.29 (s, 3H), 2.11 (d, J = 1.0 Hz, 3H), 2.10 – 2.02 (m, 2H), 1.19 (d, J = 6.2 Hz, 2H). 13C NMR (126 MHz, MeOD) δ 152.31; 122.17, 121.43, 119.62, 118.61, 110.84, 106.26, 104.07, 99.74, 97.42, 77.30, 72.06, 70.66; 65.12, 60.19, 52.72, 50.23, 48.11, 47.94, 47.77, 47.60, 47.43, 47.26, 47.09, 38.90, 37.47, 16.76, 11.51, 9.67. ESI-HRMS for C 36 H 43 N6O4 +(M) calculated mass: 623.3346; found: 623.3348. 2-((E)-2-(2,5-dimethyl-1-(4-(1-(^-mannopyranosyl-thioethyl)-1H-1,2,3-triazol-4-yl)phenyl)-1H-pyrrol-3-yl)vinyl)-6-(dimethylamino)-1-methylquinolin-1-ium trifluoroacetate (man-S-C2- PYR, 12). To a solution of (E)-6-(dimethylamino)-2-(2-(1-(4-ethynylphenyl)-2,5-dimethyl-1H-pyrrol-3-yl)vinyl)-1-methylquinolin-1-ium iodide (1 eq., 50.8 mg, 0.095 mmol) in THF / H2O (1:1, 12 mL) was added CuSO4^5H2O (0.1 eq., 2.3 mg, 0.0095 mmol), sodium ascorbate (0.5 eq., 9.4 mg, 0.0477 mmol), THPTA (0.1 eq., 4.1 mg, 0.0095 mmol) and 2-azidoethyl^-thiomannopyranoside (Wang et al., Org. Biomol. Chem.9 (2011) 2219-2226) (2 eq., 50.6 mg, 0.1908 mmol). The reaction mixture was kept stirring at 100 °C in a microwave (150 W) for 45 min. The mixture was cooled, dried under vacuum, and then purified by C18 column flash chromatography using a mobile phase of H2O (+0.1% TFA) / CH3CN (+0.1% TFA) 90:10 to H2O (+0.1% TFA) / CH3CN (+0.1% TFA) 20:80 para obtener un producto sólido rojo oscuro (15 mg, 20 %). 1 H RMN (400 MHz, DMSO) δ 8.76 (s, 1H), 8.53 (d, J = 9.3 Hz, 1H), 8.47 (d, J = 9.3 Hz, 1H), 8.24 (d, J = 9.8 Hz, 1H), 8.11 (d, J = 15.1 Hz, 1H), 8.04 (s, 1H), 8.02 (s, 1H), 7.62 (dd, J = 9.7, 3.0 Hz, 1H), 7.49 – 7.44 (m, 2H), 7.27 (s, 1H), 7.24 (d, J = 3.4 Hz, 2H), 6.76 (s, 1H), 5.28 (s, 1H), 4.38 (s, 3H), 3.82 – 3.74 (m, 2H), 3.71 (s, 2H), 3.51 (dd, J = 11.6, 7.0 Hz, 1H), 3.41 – 3.38 (m, 2H), 3.18 (t, J = 6.8 Hz, 2H), 2.29 (s, 3H), 2.07 (s, 3H). 13 C RMN (126 MHz, DMSO) δ 158.53, 158.26, 152.06, 149.33, 145.70, 140.37, 139.38, 136.76, 136.53, 131.95, 131.82, 131.56, 129.27, 128.98, 126.60, 122.85, 121.91, 120.61, 120.03, 119.65, 112.23, 106.90, 105.28, 86.02, 75.38, 72.18, 71.94, 67.73, 61.75, 49.92, 40.59, 40.49, 40.42, 40.33, 40.25, 40.16, 40.08, 39.99, 39.92, 39.83, 39.66, 39.49, 38.93, 31.38, 13.17, 11.33. ESI-HRMS para C 36 H 43 N6O5S +(M) calculated mass: 671.3016; found: 671.3069 Trifluoroacetate (gal-S-C2-PYR, 13). To a solution of (E)-6-(dimethylamino)-2-(2-(1-(4-ethynylphenyl)-2,5-dimethyl-1H-pyrrol-3-yl)vinyl)-1-methylquinolin-1-ium iodide (1 eq; 41 mg; 0.077 mmol) in THF / H2O (1:1, 3 mL) CuSO4^5H2O was added. (0.1 eq; 1.92 mg; 0.008 mmol), sodium ascorbate (0.5 eq; 7.62 mg; 0.038 mmol), THPTA (0.1 eq; 3.34 mg; 0.008 mmol) and 2-azidoethyl thiogalactopyranoside (Wang et al., Org. Biomol. Chem.9 (2011) 2219-2226) (2eq; 40.9 mg; 0.154 mmol). The reaction mixture was kept stirring at 100 °C in a microwave (150 W) for 45 min. The mixture was cooled, dried under vacuum, and purified using a Teledyne Isco 15.5 g HP C18 automated column (VC 13.5 mL – 30 mL / min).The solvents used for purification were A) 0.5% trifluoroacetic acid in Milli-Q water, and B) 0.5% trifluoroacetic acid in acetonitrile. The method employed maintained a flow rate of 30 mL / min, starting with 90% aqueous solvent for 1 minute, which was gradually reduced to 20% over 13 minutes. The solvent concentration was maintained at 20% for 3 minutes, after which the solvent was returned directly to an isocratic mixture (detection wavelength: 214 and 254 nm). A red solid (20 mg, 38%) was obtained. 1 H NMR (400 MHz, Methanol-d4) δ 8.61 (s, 1H), 8.43 (d, J = 9.2 Hz, 1H), 8.22 (d, J = 9.2 Hz, 1H), 8.17 (d, J = 9.7 Hz, 1H), 8.10 – 7.96 (m, 4H), 7.63 (dd, J = 9.7, 2.8 Hz, 1H), 7.38 (d, J = 8.3 Hz, 2H), 7.23 – 7.09 (m, 2H), 6.61 (s, 1H), 4.81 (q, J = 6.7 Hz, 2H), 4.45 (d, J = 9.7 Hz, 1H), 4.40 (s, 3H), 3.92 (d, J = 3.1 Hz, 2H), 3.87 – 3.82 (m, 1H), 3.78 (d, J = 4.5 Hz, 1H), 3.75 (d, J = 4.4 Hz, 1H), 3.67 – 3.59 (m, 3H), 3.51 (dd, J = 9.2, 3.3 Hz, 1H), 3.17 (s, 6H), 2.29 (s, 3H), 2.11 (s, 3H).13 C NMR (126 MHz, MeOD) δ 130.67, 128.80, 123.07, 122.76, 117.00, 115.59, 103.53, 99.65, 94.46, 77.71, 75.44, 71.35, 64.02,000; 34.53, 32.37, 30.41, 30.19, 29.91, 29.86, 29.80, 27.88, 27.88, 26.26, 25.57, 23.34, 14.15. ESI-HRMS for C 36 H 43 N6O5S +(M) Calculated mass: 671.3016; found mass: 671.3015. 1-(3-Ethynylphenyl)-2,5-Dimethyl-1H-pyrrole. To a stirred solution of 3-ethynylaniline (Sigma-Aldrich, CAS: 54060-30-9) (1 eq., 3 g; 25.6 mmol) were added 2,5-Hexadione (1.2 eq; 3.5 g; 30.72 mmol) and Amberlite IR120 (1.5 g). The reaction was maintained at room temperature, without solvent, for 24 hours. Once the reaction was complete, the mixture was diluted with ethyl acetate and filtered to recover the catalyst. The organic phase was washed with a saturated sodium bicarbonate solution and brine solution, dried with anhydrous Na2SO4, and concentrated under vacuum. The organic phase was purified by silica-gel column chromatography (0.04–0.063 µm) using a mobile phase of 100% hexane to hexane / ethyl acetate (30:1) to obtain a pure white product (2.5 g, 52%). 1H NMR (400 MHz, Chloroform-d) δ 7.43 (d, J = 7.7 Hz, 1H), 7.33 (t, J = 7.8 Hz, 1H), 7.12 (d, J = 7.9 Hz, 1H), 5.81 (s, 2H), 3.03 (s, 1H), 1.94 (s, 6H). 13 C NMR (101 MHz, CDCl3) δ 139.28, 131.92, 131.51, 129.28, 129.02, 123.31, 106.12, 82.73, 78.36, 13.11, 1.15. ESI-HRMS para C 14 H 13 N (M) mass calculated: 194.1048; encontrada: 194.0961 1-(3-ethynylphenyl)-2,5-dimethyl-1H-pyrrol-3-carbaldehído To a stirred solution of 1-(3-ethynylphenyl)-2,5-dimethyl-1H-pyrrole (1 eq; 2.5 g; 12.81 mmol) in anhydrous DMF (1 eq; 936 mg; 12.81 mmol) and anhydrous toluene (17.5 mL), POCl3 (1 eq; 1.96 g; 12.81 mmol) was added dropwise. The solution was heated at 110 °C for 6 hours. The mixture was cooled to room temperature. A saturated solution of AcONa (50 mL) was added, and the mixture was stirred vigorously for 20 minutes. 250 mL of dichloromethane and solid K2CO3 were added, and the mixture was stirred. The organic phase was washed with NaHCO3 and brine, and the organic phase was dried with anhydrous Na2SO4 and evaporated under vacuum. The residue was purified by silica gel column chromatography using a mobile phase of hexane / ethyl acetate (4:1) to hexane / ethyl acetate (2:1) to obtain a clear oil (1.6 g, 32%). 1H NMR (400 MHz, Chloroform-d) δ 9.79 (d, J = 2.9 Hz, 1H), 7.63 (d, J = 7.9 Hz, 0H), 7.52 – 7.49 (m, 1H), 7.43 (dt, J = 14.2, 7.2 Hz, 13.1Hz). (d, J = 7.9 Hz, 1H), 6.62 (d, J = 8.2 Hz, 0H), 6.31 (d, J = 3.9 Hz, 1H), 3.11 (s, 0H), 2.22 (d, J = 10.5 Hz, 3H), 1.92 (d, J = 10.6 Hz, 3H). 13 C NMR (101 MHz, CDCl3) δ 185.32, 132.69, 131.53, 130.96, 129.80, 128.58, 127.57, 122.15, 119.66, 12.72, 11.29. ESI-HRMS for C 15 H 13 NO (MH + ) calculated mass: 224.0997; found: 224.1118 Iodide of (E)-6-(dimethylamino)-2-(2-(1-(3-ethynylphenyl)-2,5-dimethyl-1H-pyrrole-3-yl)vinyl)-1- methylquinoline-1-io To a solution of 6-(dimethylamino)-1,2-dimethylquinolin-1-iodine (1 eq; 406 mg; 1.24 mmol) and 1-(4-ethynylphenyl)-2,5-dimethyl-1H-pyrrole-3-carbaldehyde (1.8 eq; 500 mg; 2.24 mmol) in methanol (40 mL), piperidine (10 drops) was added, and the reaction mixture was heated and maintained under reflux (65 °C) for 24 hours. The reaction mixture was cooled to room temperature and then purified using a Teledyne Isco 15.5g HP C18 automated reversed-phase column (VC 13.5 mL – 30 mL / min). The solvents used for purification were A) 0.5% trifluoroacetic acid in Milli-Q water, B) trifluoroacetic acid 0.5% in acetonitrile. The method used was as follows: flow of 30mL / min. Gradient of 70% of the aqueous solvent for 1 minute and gradual reduction to 20% for 13 minutes, when it passes directly to 0% for 3 minutes after which it is kept in an isocratic mixture for one minute to equilibrate the column (λ detection: 214 and 254 nm).If I get a red solid (100 mg, 20%). 1 H NMR (400 MHz, Methanol-d4) δ 8.42 (d, J = 9.2 Hz, 1H), 8.19 (d, J = 9.2 Hz, 1H), 8.15 (d, J = 9.7 Hz, 1H), 7.98 (d, J = 15.2 Hz, 1H), 7.66 – 7.55 (m, 3H), 7.39 (s, 1H), 7.31 (d, J = 7.9 Hz, 1H), 7.17 (d, J = 15.2 Hz, 1H), 7.13 (d, J = 2.9 Hz, 1H), 6.58 (s, 1H), 4.38 (s, 3H), 3.68 (s, 1H), 3.15 (s, 6H), 2.24 (s, 3H), 2.05 (s, 3H). 13 C NMR (101 MHz, MeOD) δ 153.67, 150.83, 141.74, 140.23, 137.48, 133.53, 133.43, 133.09, 132.41, 131.10, 130.72, 129.78, 125.46, 121.04, 120.70, 120.02, 112.43, 107.63, 105.51, 80.61, 40.30, 38.91, 12.81, 10.98. ESI-HRMS for C 28 H 28 N3(M) calculated mass: 406.2361; encontrada: 406.2266. Trifluoroacetate de 2-((E)-2-(2,5-dimethyl-1-(3-(1-xylosyl)-1H-1,2,3-triazol-4-yl)phenyl)-1H- pyrrol-3-yl)vinyl)-6-(dimethylamino)-1-methylquinoline-1-io (xyl-3-PYR, 15). To a solution of (E)-6-(dimethylamino)-2-(2-(1-(3-ethynylphenyl)-2,5-dimethyl-1H-pyrrole-3-yl)vinyl)-1-methylquinolin-1-iodide (1 eq; 50 mg; 0.096 mmol) in THF / H2O (1:1, 3 mL) were added CuSO4^5H2O (0.1 eq; 2.39 mg; 0.009 mmol), sodium ascorbate (0.5 eq; 9.5 mg; 0.048 mmol), THPTA (0.1 eq; 4.1 mg; 0.009 mmol) and 1-azidoxylose (Apollo Scientific, CAS: 51368-20-8) (2 eq; 33.6 mg; 0.192 mmol). The reaction mixture was kept stirring at 100 °C in a microwave (150 W) for 45 min. The mixture was cooled, dried under vacuum, and purified using a Teledyne Isco 15.5 g HP C18 automated column (VC 13.5 mL – 30 mL / min). The solvents used for purification were A) 0.5% trifluoroacetic acid in Milli-Q water, B) 0.5% trifluoroacetic acid in acetonitrile.In the method used, a flow rate of 30 mL / min was maintained, starting with 90% aqueous solvent for 1 minute, which was gradually reduced to 20% over 13 minutes and held for 3 minutes. After this time, the mixture was returned directly to an isocratic mixture (λ detection: 214 and 254 nm). A red solid (11 mg, 16%) was obtained. 1H RMN (400 MHz, Metanol-d4) δ 8.67 (s, 1H), 8.43 (d, J = 9.2 Hz, 1H), 8.22 (d, J = 9.2 Hz, 1H), 8.18 (s, 1H), 8.06 – 8.00 (m, 3H), 7.82 (d, J = 1.7 Hz, 1H), 7.30 (dd, J = 7.4, 1.5 Hz, 1H), 7.23 – 7.13 (m, 3H), 6.61 (s, 1H), 5.57 (dd, J = 9.2, 3.0 Hz, 1H), 4.05 (dd, J = 11.3, 5.4 Hz, 2H), 3.95 (td, J = 9.1, 2.9 Hz, 2H), 3.71 (ddd, J = 10.6, 9.0, 5.4 Hz, 2H), 3.58 – 3.47 (m, 3H), 3.16 (s, 6H), 2.29 (s, 3H), 2.10 (s, 3H). 13C RMN (101 MHz, MeOD) δ 153.80, 150.86, 141.73, 140.40, 139.68, 137.66, 133.55, 133.14, 131.52, 128.94, 126.18, 122.88, 122.06, 121.08, 120.71, 120.03, 112.33, 107.68, 105.46, 90.44, 78.63, 74.00, 70.70, 69.93, 40.30, 38.90, 12.88, 11.05. ESI- HRMS C 33 H 37 N6O4 +(M) calculated mass: 581.2876; found: 581.2880 2-((E)-2-(2,5-dimethyl-1-(3-(1-(6-deoxyglucosyl)-1H-1,2,3-triazol-4-yl)phenyl)-1H-pyrrol-3-yl)vinyl)-6-(dimethylamino)-1-methylquinolin-1-io trifluoroacetate (6dglc-3-PYR, 16). To a solution of (E)-6-(dimethylamino)-2-(2-(1-(3-ethynylphenyl)-2,5-dimethyl-1H-pyrrole-3-yl)vinyl)-1-methylquinolin-1-iodide (1 eq; 40 mg; 0.077 mmol) in THF / H2O (1:1, 3 mL) were added CuSO4^5H2O (0.1 eq; 1.92 mg; 0.008 mmol), sodium ascorbate (0.5 eq; 7.62 mg; 0.038 mmol), THPTA (0.1 eq; 3.34 mg; 0.008 mmol) and 1-azido-6-deoxyglucose (Arévalo-Ruiz et al., Chem. Eur. J. 2017, 23, 2157) (2 eq; 40.9 mg; 0.154 mmol). The reaction mixture was kept stirring at 100 °C in a microwave (150 W) for 45 min. The mixture was cooled, dried under vacuum, and purified using a Teledyne Isco 15.5 g HP C18 automated column (VC 13.5 mL – 30 mL / min).The solvents used for purification were A) 0.5% trifluoroacetic acid in Milli-Q water, and B) 0.5% trifluoroacetic acid in acetonitrile. The method employed maintained a flow rate of 30 mL / min, starting with 90% aqueous solvent for 1 minute, which was gradually reduced to 20% over 13 minutes. The solvent concentration was maintained at 20% for 3 minutes, after which the solvent was returned directly to an isocratic mixture (detection wavelength: 214 and 254 nm). A red solid (15 mg, 32%) was obtained. 1 H NMR (400 MHz, Methanol-d4) δ 8.66 (s, 1H), 8.43 (d, J = 9.2 Hz, 1H), 8.23 ​​(s, 1H), 8.15 (s, 1H), 8.05 – 7.99 (m, 2H), 7.81 (t, J = 1.7 Hz, 2H), 7.69 – 7.61 (m, 3H), 7.29 (ddd, J = 7.8, 2.0, 0.9 Hz, 2H), 7.20 – 7.13 (m, 2H), 6.60 (s, 1H), 5.63 (d, J = 9.2 Hz, 1H), 3.97 (t, J = 9.2 Hz, 1H), 3.68 – 3.60 (m, 1H), 3.54 (t, J = 9.1 Hz, 1H), 3.27 – 3.18 (m, 2H), 3.16 (s, 6H), 2.29 (s, 3H), 2.09 (s, 3H), 1.34 (d, J = 6.1 Hz, 3H). 13C NMR (126 MHz, MeOD) δ 153.74, 150.83, 147.61, 141.70, 140.37, 139.65, 137.68; 127.15, 126.16, 122.86, 122.03, 121.04, 120.70, 120.02, 112.29, 107.67, 105.46, 89.75, 78.27; 40.30, 38.89, 18.12, 12.90, ESI-HRMS for C 34 H 39 N6O4 +(M) calculated mass: 595.3033; found: 595.3008. 2-((E)-2-(2,5-dimethyl-1-(3-(1-fucosyl)-1H-1,2,3-triazol-4-yl)phenyl)-1H-pyrrol-3-yl)vinyl)-6-(dimethylamino)-1-methylquinolin-1-ium trifluoroacetate (fuc-3-PYR, 17). To a solution of (E)-6-(dimethylamino)-2-(2-(1-(3-ethynylphenyl)-2,5-dimethyl-1H-pyrrole-3-yl)vinyl)-1-methylquinolin-1-iodide (1 eq; 50 mg; 0.096 mmol) in THF / H2O (1:1, 3 mL) were added CuSO4^5H2O (0.1 eq; 2.39 mg; 0.009 mmol), sodium ascorbate (0.5 eq; 9.5 mg; 0.192 mmol), THPTA (0.1 eq; 4.1 mg; 0.009 mmol) and 1-azido-L-fucose (Synthose, CAS: 66347-26-0) (2 eq; 36 mg; 0.192 mmol). The reaction mixture was kept stirring at 100 °C in a microwave (150 W) for 45 min. The mixture was cooled, dried under vacuum, and purified using a Teledyne Isco 15.5 g HP C18 automated column (VC 13.5 mL – 30 mL / min). The solvents used for purification were A) 0.5% trifluoroacetic acid in Milli-Q water, B) 0.5% trifluoroacetic acid in acetonitrile.In the method used, a flow rate of 30 mL / min was maintained, starting with 90% aqueous solvent for 1 minute, which was gradually reduced to 20% over 13 minutes and held for 3 minutes. After this time, the mixture was returned directly to an isocratic mixture (λ detection: 214 and 254 nm). A red solid (12 mg, 18%) was obtained. 1 H NMR (400 MHz, Methanol-d4) δ 8.68 (s, 1H), 8.45 (s, 1H), 8.23 ​​(d, J = 9.2 Hz, 1H), 8.17 (d, J = 9.7 Hz, 1H), 8.06 – 7.99 (m, 2H), 7.81 (s, 1H), 7.69 (d, J = 7.9 Hz, 1H), 7.67 – 7.62 (m, 2H), 7.30 (d, J = 7.7 Hz, 1H), 7.21 (d, J = 15.2 Hz, 1H), 7.15 (d, J = 2.9 Hz, 1H), 6.61 (s, 1H), 5.60 (d, J = 9.2 Hz, 1H), 4.13 (t, J = 9.3 Hz, 1H), 4.00 (q, J = 6.5 Hz, 2H), 3.79 (d, J = 3.0 Hz, 2H), 3.73 (dd, J = 9.5, 3.3 Hz, 2H), 2.30 (s, 3H), 2.10 (s, 3H), 1.32 (d, J = 6.4 Hz, 3H). 13C NMR (101 MHz, MeOD) δ 141.72; 75.44, 73.02, 71.34, 40.53, 40.30, 16.80, 12.89, 11.07. ESI-HRMS for C 34 H 39 N6O4 +(M) Calculated mass: 595.3033; found: 595.3016. 1-(2-Ethynylphenyl)-2,5-Dimethyl-1H-pyrrole. To a stirred solution of 2-ethynylaniline (Sigma-Aldrich, CAS: 52670-38-9) (1.2 eq., 0.58 g, 4.97 mmol) in tetrahydrofuran (3 mL) were added 2,5-Hexadione (1 eq., 0.49 mL, 4.14 mmol) and I2 (0.1 eq., 0.1 g, 0.41 mmol). The reaction was maintained at room temperature for 24 hours. Once the reaction was complete, the mixture was extracted with a saturated sodium bicarbonate solution and brine solution, dried with anhydrous Na2SO4, and concentrated in vacuo. The organic phase was purified by silica-gel column chromatography (0.063-0.200 µm) using a mobile phase of hexane / ethyl acetate 12:1 to hexane / ethyl acetate 10:1 to obtain a pure white product (138 mg, 14%). 1 H NMR (400 MHz, CDCl3) δ 7.53 (dd, J = 7.6, 1.7 Hz, 1H), 7.34 (dd, J = 7.7, 1.7 Hz, 1H), 7.31 – 7.25 (m, 1H), 7.13 (dd, J = 7.7, 1.5 Hz, 1H), 5.82 (s, 2H), 2.92 (s, 1H), 1.91 (s, 6H); 13C NMR (101 MHz, CDCl3) δ 141.37, 133.62, 129.54, 129.37, 128.88, 128.09, 122.73, 105.53, 81.25, 79.66, 77.45, 77.14. 76.82, 12.69; ESI-HRMS for C 14 H 13 N (MH + ) calcd: 196.1048; found: 196.1117. 1-(2-ethynylphenyl)-2,5-dimethyl-1H-pyrrole-3-carbaldehyde To a stirred solution of 1-(2-ethynylphenyl)-2,5-dimethyl-1H-pyrrole (1 eq., 166 mg, 0.851 mmol) and dry DMF (1 eq., 0.065 mL, 0.851 mmol) in anhydrous toluene (0.53 mL), POCl3 (1 eq., 130 mg, 0.851 mmol) was added dropwise. The solution was heated to 110°C for 2 hours. The mixture was cooled to room temperature. A saturated NaOAc solution (6 mL) was added, and the mixture was stirred vigorously for 20 minutes. 30 mL of dichloromethane and 355 mg of K2CO3 (s) were then added. The mixture was stirred and the organic phase was extracted with NaHCO3 and brine and then evaporated and purified by silica-gel column chromatography (0.063-0.200 µm) using a mobile phase of hexane / ethyl acetate 4:1 to hexane / ethyl acetate 2:1 to obtain a solid product (85.5 mg, 45%). 1 H NMR (400 MHz, CDCl3) δ 9.89 (s, 1H), 7.68 (dd, J = 7.5, 1.8 Hz, 1H), 7.57 – 7.44 (m, 2H), 7.24 (dd, J = 7.3, 1.9 Hz, 1H), 6.40 (d, J = 1.2 Hz, 1H), 3.06 (s, 1H), 2.27 (s, 3H), 1.98 (d, J = 1.1 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 185.28, 139.18, 133.82, 130.98, 129.92, 129.17, 128.76, 122.38, 121.98, 105.62, 82.36, 78.56, 77.38, 77.07, 76.75, 29.70, 12.31, 10.89; ESI-HRMS for C 15 H 13 NO (MH + ) calcd: 224.0997; found: 224.1125. (E)-6-(dimethylamino)-2-(2-(1-(2-ethynylphenyl)-2,5-dimethyl-1H-pyrrol-3-yl)vinyl)-1-methylquinolin- 1-io To a solution of 6-(dimethylamino)-1,2-dimethylquinolin-1-iodine (1 eq., 69.5 mg, 0.212 mmol) and 1-(2-ethynylphenyl)-2,5-dimethyl-1H-pyrrole-3-carbaldehyde (1.8 eq., 0.85 mg, 0.381 mmol) in methanol (10 mL), piperidine (2-3 drops) was added, and the reaction mixture was heated and held under reflux for 27 hours. The reaction mixture was cooled to room temperature and then purified by silica gel column chromatography (0.04-0.063 µm) using a 100% CH2Cl2a CH2Cl2 / MeOH 20:1 mobile phase to obtain a dark red product (62 mg, 40%). 1H NMR (400 MHz, DMSO) δ 8.52 (d, J = 9.3 Hz, 1H), 8.45 (d, J = 9.3 Hz, 1H), 8.22 (d, J = 9.7 Hz, 1H), 8.08 (d, J = 15.1 Hz, 1Hz, 75). 7.6, 1.8 Hz, 1H), 7.64 (dd, J = 7.6, 1.8 Hz, 1H), 7.58 – 7.56 (m, 1H), 7.43 (dd, J = 7.7, 1.4 Hz, 1H), 7.23 (dt, J = 7.7, 1.9 Hz), Hz (d, J = 3.2 Hz, 1H), 6.75 – 6.72 (m, 1H), 4.36 (s, 3H), 3.39 (d, J = 7.3 Hz, 1H), 3.12 (s, 6H), 2.19 (s, 3H), 1.97 – 1.95 (m, 3H); 13 C NMR (101 MHz, DMSO) δ 152.01, 149.24, 140.25, 139.33, 136.62, 134.02, 131.85, 131.70, 130.87, 121.81, 120.60, 119.99, 119.52, 112.17, 106.92, 105.04, 85.71, 52.58, 46.20, 40.71, 40.66, 40.50, 40.5, 40.5, 40.3. 40.29, 40.24, 40.04, 39.82, 39.62, 39.41, 39.06, 33.75, 12.76, 11.03, 9.14, 7.79; ESI- HRMS for C 28 H 28 N3(M) calcd: 406.2361; found: 406.2289. Trifluoroacetate of 2-((E)-2-(2,5-dimethyl-1-(2-(1-(xylopyranosyl)-1H-1,2,3-triazol-4-yl)phenyl)- 1H-pyrrol-3-yl)vinyl)-6-(dimethylamino)-1-methylquinoline-1-Poxyl-1-R, To a solution of (E)-6-(dimethylamino)-2-(2-(1-(2-ethynylphenyl)-2,5-dimethyl-1H-pyrrol-3-yl)vinyl)-1-methylquinolin-1-ium (1 eq., 26.6 mg, 0.05 mmol) in THF / H2O (1:1, 8 mL) CuSO4^5H2O was added (0.1 eq., 1.24 mg, 0.005 mmol), sodium ascorbate (0.5 eq., 4.93 mg, 0.025 mmol), THPTA (0.1 eq., 2.16 mg, 0.005 mmol), and β-D-xylopyranosyl azide (Apollo Scientific, CAS: 51368-20-8) (2 eq., 17.43 mg, 0.099 mmol). The reaction mixture was kept stirring at 100 °C in a microwave (150 W) for 80 min. The mixture was cooled, dried under vacuum, and then purified by C18 column flash chromatography using a mobile phase of H2O (+0.1% TFA) / CH3CN (+0.1% TFA) 90:10 to H2O (+0.1% TFA) / CH3CN (+0.1% TFA) 20:80 to obtain a dark red solid product (5.5 mg, 16%). 1H RMN (400 MHz, DMSO) δ 8.54 (dd, J = 9.2, 4.3 Hz, 1H), 8.45 (dd, J = 10.9, 9.3 Hz, 1H), 8.31 (ddd, J = 7.6, 5.6, 1.6 Hz, 1H), 8.25 (d, J = 9.7 Hz, 1H), 8.08 (dd, J = 18.2, 15.1 Hz, 1H), 7.71 (td, J = 7.6, 1.4 Hz, 1H), 7.63 (ddd, J = 11.0, 6.5, 2.6 Hz, 2H), 7.46 (dt, J = 7.8, 1.6 Hz, 1H), 7.31 (dd, J = 15.2, 5.0 Hz, 1H), 7.24 (d, J = 3.0 Hz, 1H), 6.84 (s, 1H), 6.65 (d, J = 30.0 Hz, 1H), 5.41 (d, J = 9.1 Hz, 1H), 4.41 (s, 3H), 3.43 – 3.22 (m, 5H), 3.15 (s, 6H), 2.03 (d, J = 8.4 Hz, 3H), 1.83 (d, J = 2.9 Hz, 3H). 13 C RMN (126 MHz, MeOD) δ 152.14, 149.53, 142.25, 140.60, 138.33, 134.80, 133.85, 131.80, 131.16, 129.79, 129.39, 129.35, 129.29, 127.82, 121.68, 120.64, 120.21, 119.86, 118.75, 111.99, 111.72, 106.14, 104.73, 104.60, 88.56, 77.01, 72.78, 69.32, 68.26, 48.11, 47.94, 47.77, 47.60, 47.43, 47.26, 47.09, 38.90, 37.75, 10.93, 9.14. ESI- HRMS para C 33 H 37 N6O4 +(M) Calculated mass: 581.2876; found: 581.2895. 2-(2,5-dimethyl-1H-pyrrole-1-yl)-5-ethynylpyridine. Iodine (0.1 eq, 177 mg, 0.7 mmol) was added to a solution of 5-ethynylpyridin-2-amine (Indagoo CAS: 82454-61-3) (1 eq, 1 g, 8.47 mmol) and hexane-2,5-dione (1.2 eq, 1.15 g, 10.164 mmol) in THF (10 mL) in a round-bottom flask. The mixture was kept under stirring and reflux (50 °C) in an inert argon atmosphere for 20 hours until the starting material was completely consumed. After the reaction was complete, the mixture was diluted with DCM and treated with NaSO3, then washed with NaHCO3 and brine. The organic phase was dried with anhydrous Na2SO4 and purified by flash silica gel chromatography using Hexane / EtOAc (100:0 to 30:1) as the mobile phase to obtain a white solid (150 mg, 9%). 1 H NMR (400 MHz, Chloroform-d) δ 8.74 (d, J = 1.8 Hz, 1H), 7.92 (dd, J = 8.2, 2.3 Hz, 1H), 7.22 (dd, J = 8.2, 0.7 Hz, 1H), 5.95 (s, 2H), 3.31 (s, 1H), 2.19 (d, J = 3.9 Hz, 6H).13 C NMR (101 MHz, CDCl3) δ 152.40, 140.98, 128.67, 121.06, 107.63, 81.37, 79.89, 13.33. ESI-HRMS for C 13 H 12 N2(M) calculated mass: 197.1079; found: 197.1079. 1-(5-ethinylpyridin-2-yl)-2,5-dimethyl-1H-pyrrole-3-carbaldehyde To a solution of 2-(2,5-dimethyl-1H-pyrrole-1-yl)-5-ethinylpyridine (1 eq; 150 mg; 0.765 mmol) in anhydrous DMF (1 eq; 55.9 mg; 0.765 mmol) and anhydrous toluene (1.25 mL), POCl3 (1 eq; 117.30 mg; 0.765 mmol) was added dropwise. The solution was heated to 110 °C for 20 hours. The mixture was cooled to room temperature. A saturated solution of NaOCl (10 mL) was added and the mixture was stirred vigorously for 20 minutes. 50 mL of dichloromethane and 430 mg of solid K2CO3 were added, and the mixture was stirred. The organic phase was washed with NaHCO3 and brine, and the organic phase was dried with anhydrous Na2SO4 and evaporated under vacuum. The residue was purified by silica gel flash column chromatography using a hexane / ethyl acetate mobile phase (4:1) to obtain a clear oil (70 mg, 41%). 1H NMR (400 MHz, Methanol-d4) δ 9.80 (d, J = 10.3 Hz, 1H), 8.72 (s, 1H), 8.20 – 8.06 (m, 1H), 7.47 (q, J = 10.6, 9.9 Hz, 1H), 6.5 (J. Hz, 1H), 3.94 (d, J = 1.3 Hz, 1H), 2.41 – 2.33 (m, 3H), 2.07 (d, J = 9.7 Hz, 3H). 13 C NMR (101 MHz, MeOD) δ 186.11, 152.16, 142.03, 122.36, 105.73, 82.89, 78.64, 11.26, 9.64. ESI-HRMS for C 14 H 12 N2O (M) calculated mass: 225.1028; found: 225.1025. (E)-6-(dimethylamino)-2-(2-(1-(5-ethynylpyridin-2-yl)-2,5-dimethyl-1H-pyrrole-3-yl)vinyl)-1- Piperidine (10 drops) was added to a solution of 6-(dimethylamino)-1,2-dimethylquinolin-1-iodide (1 eq; 56 mg; 0.172 mmol) and 1-1-(5-ethynylpyridin-2-yl)-2,5-dimethyl-1H-pyrrole-3-carbaldehyde (1.8 eq; 70 mg; 0.31 mmol) in methanol (20 mL), and the reaction mixture was heated and held under reflux (65 °C) for 16 hours. The reaction mixture was cooled to room temperature and then purified using a Teledyne Isco 15.5 g HP C18 automated reversed-phase column (VC 13.5 mL – 30 mL / min). The solvents used for purification were A) 0.5% trifluoroacetic acid in Milli-Q water, B) 0.5% trifluoroacetic acid in acetonitrile. The method used was as follows: flow rate of 30 mL / min.A gradient of 70% aqueous solvent was applied for 1 minute, followed by a gradual reduction to 20% over 13 minutes, then directly to 0% for 3 minutes, after which the mixture was held in an isocratic mixture for 1 minute to equilibrate the column (λ detection: 214 and 254 nm). A red solid (40 mg, 45%) was obtained. 1 H NMR (400 MHz, Methanol-d4) δ 8.71 (d, J = 2.1 Hz, 1H), 8.37 (d, J = 9.1 Hz, 1H), 8.10 (dt, J = 9.6, 3.3 Hz, 3H), 7.85 (d, J = 15.2 Hz, 1H), 7.55 (dd, J = 9.7, 3.0 Hz, 1H), 7.40 (d, J = 8.2 Hz, 1H), 7.08 – 7.01 (m, 2H), 6.53 (s, 1H), 4.31 (s, 3H), 3.94 (s, 1H), 3.09 (s, 6H), 2.27 (s, 3H), 2.10 (s, 3H). 13 C NMR (101 MHz, MeOD) δ 153.41, 150.96, 150.71, 143.25, 141.70, 139.47, 137.02, 133.31, 130.73, 123.36, 122.87, 121.18, 120.90, 120.05, 113.06, 107.46, 106.31, 84.13, 80.12, 40.24, 38.92, 12.99, 11.04. ESI-HRMS for C 27 H 27 N4 +(M) masa calculada: 407.2236; encontrada: 407.2227. Trifluoroacetato de 2-((E)-2-(2,5-dimetil-1-(5-(1-xilosil)-1H-1,2,3-triazol-4-il)piridin-2-il)- 1H-pirrol-3-il)vinil)-6-(dimetilamino)-1-metilquinolin-1-io (xyl-2N-4-PYR, 7) To a solution of (E)-6-(dimethylamino)-2-(2-(1-(5-ethynylpyridin-2-yl)-2,5-dimethyl-1H-pyrrol-3-yl)vinyl)-1-methylquinolin-1-ium iodide (1 eq; 30 mg; 0.058 mmol) in THF / H2O (1:1, 3 mL) was added CuSO4^5H2O (0.1 eq; 1.44 mg; 0.006 mmol), sodium ascorbate (0.5 eq; 5.7 mg; 0.029 mmol), THPTA (0.1 eq; 2.51 mg; 0.006 mmol), and β-D-xylopyranosyl azide (Apollo Scientific, CAS: 51368-20-8) (2eq; 20.3 mg; 0.116 mmol). The reaction mixture was kept stirring at 100 °C in a microwave oven (150 W) for 45 min. The mixture was cooled, dried under vacuum, and then purified using a Teledyne Isco 15.5 g HP C18 automated column (VC 13.5 mL – 30 mL / min). The solvents used for purification were A) 0.5% trifluoroacetic acid in Milli-Q water, B) 0.5% trifluoroacetic acid in acetonitrile.In the method used, a flow rate of 30 mL / min was maintained, starting with 90% aqueous solvent for 1 minute, which was gradually reduced to 20% over 13 minutes and held for 3 minutes. After this time, the solution was returned directly to an isocratic mixture (λ detection: 214 and 254 nm). A red solid (15 mg, 44%) was obtained. 1 H NMR (400 MHz, Methanol-d4) δ 9.13 (d, J = 1.7 Hz, 1H), 8.80 (s, 1H), 8.51 (dd, J = 8.2, 2.3 Hz, 1H), 8.44 (d, J = 9.2 Hz, 1H), 8.19 (dd, J = 15.9, 9.5 Hz, 2H), 7.98 (d, J = 15.2 Hz, 1H), 7.63 (dd, J = 9.7, 2.8 Hz, 1H), 7.55 (d, J = 8.2 Hz, 1H), 7.21 (d, J = 15.1 Hz, 1H), 7.14 (d, J = 2.6 Hz, 1H), 6.60 (s, 1H), 5.62 (d, J = 9.2 Hz, 1H), 4.39 (d, J = 6.0 Hz, 3H), 4.06 (dd, J = 11.4, 5.4 Hz, 2H), 4.01 – 3.94 (m, 1H), 3.77 – 3.67 (m, 2H), 3.54 (q, J = 10.8, 10.0 Hz, 2H), 3.17 (d, J = 9.9 Hz, 5H), 2.34 (s, 2H), 2.16 (s, 3H). 13C NMR (126 MHz, MeOD) δ 153.56; 124.18, 123.01, 122.65, 121.15; 12.91, ESI-HRMS for C 32 H 36N7O4+ (M) calculated mass: 582.2823; found mass: 582.2817. Example 2: Biological Activity Studies. Cell Culture. Cell culture media were purchased from Gibco (Grand Island, NY, USA). Fetal bovine serum (FBS) was a product of Harlan-Seralab (Belton, UK). Supplements and other chemicals not listed in this section were obtained from Sigma Chemicals Co. (St. Louis, MO, USA). Cell culture plastics were supplied by Thermo Scientific™ BioLite. All compounds tested were dissolved in DMSO at a concentration of 10 mM and stored at -20°C until use. Cell lines were maintained in Dulbecco's modified Eagle medium (DMEM) containing glucose (1 g / L HEK-293 and MRC-5 or 4.5 g / L HPanEpiC), glutamine (2 mM), penicillin (50 IU / mL) and streptomycin (50 µg / mL), supplemented with 10% FBS. Cytotoxicity assays.The Resazurin reduction assay (alamarBlue®; Thermo Fisher Scientific) was used in 96-well microplates, as previously described in Belmonte-Reche et al. Eur. J. Med. Chem. 2022, 232, 114183. They were incubated 5 x 10. 3HEK-293, HPanEpiC, or MRC-5 cells were cultured in a total volume of 100 µl of their respective growth media with serial dilutions of the tested compounds. After 3 days of incubation (37 °C, 5% CO2 in a humidified atmosphere), 20 µl of resazurin (0.11 mg / ml in PBS) was added to each well, and the plate was incubated for a further 4 h (37 °C). Finally, 50 µl of 3% SDS was added to lyse the membranes and completely solubilize the resulting resazurin, and the fluorescence emission was read on a plate reader (exc = 550 nm; em = 590 nm). Each determination was performed in triplicate, and all experiments were repeated at least three times. In vitro antitrypanosomal activity against Trypanosoma brucei. Bloodstream forms (BSF) of T. brucei brucei 'single marker' S427 (S16) were cultured at 37°C, 5% CO2 in HMI-9 medium supplemented with 10% heat-inactivated fetal bovine serum (hiFBS). Drug susceptibility testing was performed as described in Carvalho L.and colleagues, Antimicrob Agents Chemother. 2015 Oct;59(10):6151-60. Briefly, the parasites (1 × 10. 4BSF per mL) were incubated in 96-well plates with increasing concentrations of drugs / compounds for 72 h at 37 °C, 5% CO2 in culture medium. Cell proliferation was determined using the AlamarBlue® assay (B. Raz, et al., Acta Trop 68 (1997) 139-147). The AlamarBlue assay is used to determine the drug susceptibility of African trypanosomes (Tb rhodesiense and Tb gambiense) in vitro. Fluorescence was recorded using an Infinite® F200 microplate reader (Tecan Austria GmbH, Austria) equipped with 550 nm and 590 nm filters for excitation and emission wavelengths, respectively. In vitro leishmanicidal activity against Leishmania major. Drug susceptibility experiments in L. major (MHOM / IL / 80 / Friedlin) were performed as previously described in Perez-Victoria JM et al. Antimicrob. Agents Chemother. 2011, 55 (8), 3838-3844. Briefly, 1 × 10 6Promastigotes per mL for 72 h at 28 °C in 96-well plates in modified RPMI-1640 medium (Invitrogen, Carlsbad, CA) plus 10% hiFBS, containing increasing concentrations of drugs. Cell proliferation was determined by an MTT-based assay previously described in Mosmann, TJ Immunol. Methods 1983, 65 (1-2), 55-63. Absorbance was measured at a wavelength of 540 nm. Antibiotic activity. Determination of the minimum inhibitory concentration (MIC) test. Each compound was diluted in a 10 mM DMSO stock solution and tested at concentrations ranging from 10 to 0.1 µM against the target bacteria using the broth microdilution method according to CLSI guidelines (Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically: M07-A10^; Approved Standard, 10th ed.; Clinical and Laboratory Standards Institute, Ed.(Documents / Clinical and Laboratory Standards Institute; Committee for Clinical Laboratory Standards: Wayne, PA, 2015). The compounds were serially diluted in adjusted cationic Muller-Hinton broth (cMHB, BD Difco) in 96-well microplates. The plates were then inoculated with the indicator bacteria at a final concentration of 5 x 10. 5CFU / mL and incubated at 37°C for 20 h. Water toxicity in zebrafish embryos. The lyophilized compounds were dissolved in 100% DMSO. The DMSO volume was calculated for a 100 mM stock solution. To proceed with the incubation of the compound in zebrafish embryos, the compounds were diluted in 1 mL of 0.1% DMSO / E3 medium to obtain 5 logarithmic concentrations: 0.1 μM, 1 μM, 10 μM, 100 μM, and 1 mM. Zebrafish embryo preparation: Fertilized zebrafish (Danio rerio), strain AB, embryos were collected in E3 medium in Petri dishes. At 3 hours post-fertilization (hpf), after discarding abnormal or unfertilized embryos, 20 healthy embryos per condition were placed in wells of a 24-well plate. Once the embryos were placed in each well, the E3 medium was replaced with the different dilutions previously prepared for each compound and concentration. Acute toxicity assay: The embryos were cultured from 3 hpf to 96 hpf at 28.5 °C.At 96 hours* after treatment, the LD50 mortality will be determined: LD50 (median lethal dose), calculated by fitting the sigmoidal curve to the mortality data (y = Bot + (Top-Bot) / (1 + 10 ^ (k*(x0 -Log(C)))). Bot, minimum mortality; Top, maximum mortality; k, slope of the curve; x0, estimated LC50. BMD: Reference dose. Dose at which 10% of the embryos are dead or exhibit drug-induced developmental malformations. Corresponds to BMD10. Negative control**: 1% DMSO, in three replicates. Positive controls: 3-4 DCA (3,4-dichloroaniline) at 5 different concentrations (0.1 μM, 1 μM, 10 μM, 100 μM, 1 mM). * At 24 h, coagulated eggs were removed from the well for Avoid contamination of medium E3 due to tissue decomposition. ** If the cumulative mortality of the negative control is greater than 20%, the experiment is not considered significant and must be repeated. Activity. Table 1. Antiparasitic activity of pyrvinium (PYR) and carbohydrate-4-PYR conjugates against Trypanosoma brucei and Leishmania major promastigotes, and toxicity in a healthy cell line (MRC-5). C2 stands for “-CH2-CH2-”. VT stands for “Therapeutic Window” (e.g., IC 50 MRC-5 / IC 50 T.brucei).IC50 Cells (^M) VT PYR, 1 0.048 ± 0.02 0.004 ± 0.0009 1.08 ± 0.07 23 270 glc-PYR, 2 0.081 ± 0.03 4.68 ± 1.03 7.32 ± 0.35 90 1.5 6dglc-PYR, 3 0.0031 ± 0.0044 0.016 ± 0.0004 9.08 ± 2.3 2929 567.5 6Fglc-PYR, 4 0.023 ± 0.001 0.13 ± 0.004 0.23 ± 0.15 10 1.8 fuc-PYR, 5 0.003 ± 0.002 0.83 ± 0.25 2.96 ± 0.37 987 3.6 x il-PYR, 6 0.006 ± 0.002 0.21 ± 0.11 1.86 ± 0.78 310 8.9 xyl-5N-PYR, 70.009 ± 0.001 1.40 ± 0.22.11 ± 0.3 234 1.51 maltose-PYR, 8 7.57 ± 2.39 30.16 ± 9.65 54.05 ± 5.38 7 1.8 glc-C2-PYR, 9 0.04 ± 0.024 1.53 ± 0.16 15.22 ± 2.21 381 9.9 gal-C2-PYR, 100.005 ± 0.001 1.19 ± 0.4531.66 ± 8.76 6332 26.62,6-ddglc-C2-PYR, 110.00074 ± 0.00003 0.07 ± 0.020.25 ± 0.03 338 3.6 man-S-C2-PYR, 12 0.0046 ± 0.005 0.16 ± 0.07 40.37 ± 15.63 8776 252.3 gal-S-C2-PYR, 13 0.005 ± 0.002 2.09 ± 0.67 3.88 ± 0.53 776 1.9 Suramin 0.038 ± 0.003 Eflornithin 0.026 ± 0.002 fexinidazole 0.7miltefosine 0.4 ± 0.2 Amphotericin B 0.0487

[0003] Table 2. Antiparasitic activity of PYR and the carbohydrate-2-PYR and carbohydrate-3-PYR conjugates against Trypanosoma brucei and Leishmania major promastigotes, and toxicity in a healthy cell line (MRC-5). C2 stands for “-CH2-CH2-“. VT stands for “Therapeutic Window” (e.g., IC 50 MRC-5 / IC 50 T. brucei). Antibiotic activity Table 3. Toxicity in the healthy cell line (MRC-5) and MIC (^M) of PYR and carbohydrate-4-PYR conjugates. C2 stands for “-CH2-CH2-“. IT stands for “Therapeutic Index”, as IC 50 MRC-5 / MIC strain. MIC data for clinically used antibiotics were obtained from the European Union document (EUCAST, European Committee on Antimicrobial Susceptibility Testing, Breakpoint tables for interpretation of MICs and zone diameters, Version 13.1, valid from 2023-06-29) and converted from µg / ml to concentration µM. Table 4. Toxicity in the healthy cell line (MRC-5) and MIC (µM) of PYR and carbohydrate-4-PYR conjugates. C2 stands for “-CH2-CH2-”. IT stands for “Therapeutic Index”, as IC 50 MRC-5 / MIC strain. MIC data for clinically used antibiotics were obtained from the European Union document (EUCAST, European Committee on Antimicrobial Susceptibility Testing, Breakpoint tables for interpretation of MICs and zone diameters, Version 13.1, valid from 2023-06-29) and converted from mg / ml to concentration (µM). Table 5. Toxicity in the healthy cell line (MRC-5) and MIC (µM) of PYR and carbohydrate-4-PYR conjugates. C2 stands for “-CH2-CH2-”. IT stands for “Therapeutic Index”, as IC50 MRC-5 / MIC strain. MIC data for clinically used antibiotics were obtained from the European Union document (EUCAST, European Committee on Antimicrobial Susceptibility Testing, Breakpoint tables for interpretation of MICs and zone diameters, Version 13.1, valid from 2023-06-29) and converted from mg / ml to concentration (M). Table 6. Toxicity in the healthy cell line (MRC-5) and MIC (M) of PYR and the carbohydrate-3-PYR and carbohydrate-2-PYR conjugates. C2 stands for “-CH2-CH2-”. IT stands for “Therapeutic Index”, as IC 50 MRC-5 / MIC strain. MIC data for clinically used antibiotics were obtained from the European Union document (EUCAST, European Committee on Antimicrobial Susceptibility Testing, Breakpoint tables for interpretation of MICs and zone diameters, Version 13.1, valid from 2023-06-29) and converted from ^g / ml to conc. ^M.

[0004] Table 7. Toxicity in the healthy line (MRC-5) and MIC (^M) of PYR and the carbohydrate-3-PYR and carbohydrate-2-PYR conjugates. C2 equals “-CH2-CH2-“. IT equals “Therapeutic Index”, as IC 50 MRC-5 / MIC strain. MIC data for clinically used antibiotics were obtained from the European Union document (EUCAST, European Committee on Antimicrobial Susceptibility Testing, Breakpoint tables for interpretation of MICs and zone diameters, Version 13.1, valid from 2023-06-29) and converted from mg / ml to conc. ^M.

[0005] Table 8. Toxicity in the healthy line (MRC-5) and MIC (^M) of PYR and the carbohydrate-3-PYR and carbohydrate-2-PYR conjugates. C2 equals “-CH2-CH2-“. IT equals “Therapeutic Index”, as IC 50 MRC-5 / MIC strain. MIC data for clinically used antibiotics were obtained from the European Union document (EUCAST, European Committee on Antimicrobial Susceptibility Testing, Breakpoint tables for interpretation of MICs and zone diameters, Version 13.1, valid from 2023-06-29) and converted from mg / ml to concentration. ^M. Toxicity in healthy cell lines Table 9. Cytotoxicity of PYR and carb-4-PYR conjugates. C2 is equivalent to “-CH2-CH2-“. IC 50 Cells (^M) HEK-293 HPanEpiC MRC-5 PYR, 1 0.01 ± 0.00 4.23 ± 0.21 1.08 ± 0.07 6dglc-PYR, 22.34 ± 1.64 12.45 ± 3.49 9.08 ± 2.3maltose-PYR, 8 31.88 ± 0.04 > 100 54.05 ± 5.38 glc-C2-PYR, 9 24.77 ± 1.55 > 100 15.22 ± 2.21 gal-C2-PYR, 10 3.28 ± 0.07 16.01 ± 0.31 31.66 ± 8.76 man-S-C2-PYR, 12 38.26 ± 6.71 80.96 ± 2.53 40.37 ± 15.63 gal-S-C2-PYR, 13 8.91 ± 0.41 22.86 ± 0.38 3.88 ± 0.53 Zebrafish embryo toxicity Table 10. Cytotoxicity of PYR and carb-4-PYR conjugates. C2 is equivalent to “-CH2-CH2-“. T iempoLD50 (^M) BMD (^M)PYR, 1 96 hpf 13.9 3.6 6dglc-PYR, 2 96 hpf 34.2 13.2 man-S-C2-PYR, 12 96 hpf 15,1 4,1 gal-S-C2-PYR, 13 96 hpf 50,8 37,6 Hpf is hours post-fertilization. LD50 is the lethal dose 50, the concentration at which there is 50% mortality. BMD is the dose at which 10% of embryos are dead or exhibit drug-induced developmental malformations.

Claims

1. CLAIMS 1. A compound of general formula (I) where: R1 is a -NH2 or -NR3R4 group, where R3 and R4 are independently a C1-C5 alkyl or R3 and R4 together with the N to which they are attached form an aromatic or aliphatic heterocycle of between 5 and 7 members, R2 is a glycosyl radical, where the glycosyl is selected from monoglycosyl, diglycosyl and triglycosyl, A is a group selected from -(CH2) n -, -(OCH2CH2) n - and -(SCH2CH2) n- , where n is an integer between 0 and 4, X and Y are independently selected from -CH, -CF or -N-, W is a counterion to compensate for the positive charge of the nitrogen of the aromatic ring and q is an integer selected from 1 to 3, such that the positive charges are compensated with the negative charges, the final charge of the compound of formula (I) being zero.

2. Compound, according to claim 1, wherein R1 is a –NR3R4 group, wherein R3 and R4 are independently a C1-C5 alkyl, or R3 and R4 together with the N to which they are attached form an aromatic or aliphatic heterocycle of between 5 and 7 members.

3. Compound, according to any of claims 1 to 2, wherein R3 and R4 are methyl.

4. Compound according to any of claims 1 to 3, wherein the R1 group is located at position 6 of the quinoline.

5. Compound, according to any of claims 1 to 4, wherein R2 is selected from monoglycosyl and diglycosyl.

6. A compound according to any one of claims 1 to 5, wherein the glycosyl radical is selected from glucosyl, 6-deoxyglucosyl, 6-deoxy-6-fluoroglucosyl, fucosyl, galactosyl, 2,6-dideoxyglucosyl, mannosyl, xylosyl, maltosyl, isomaltosyl, maltulosyl, cellobiosyl, gentiobiosyl, lactosyl, lactulosyl, and sucrosyl.

7. A compound according to any one of claims 1 to 6, wherein n is 0 or 1.

8. A compound according to any one of the preceding claims 1 to 7, wherein n is 0 and R2 is a monoglycosyl radical selected from glucosyl, 6-deoxyglucosyl, 6-deoxy-6-fluoroglucosyl, fucosyl, galactosyl, 2,6-dideoxyglucosyl, mannosyl, and xylosyl.

9. Compound according to any of claims 1 to 8 above, wherein n is 0 and R2 is a 6-deoxyglucosyl, 6-deoxy-6-fluoroglucosyl, fucosyl, 2,6-dideoxyglucosyl, and xylosyl radical. 10.A compound according to any one of claims 1 to 7, wherein n is 1 and R2 is a monoglycosyl radical selected from glucosyl, 6-deoxyglucosyl, 6-deoxy-6-fluoroglucosyl, fucosyl, galactosyl, 2,6-dideoxyglucosyl, mannosyl, and xylosyl.

11. A compound according to any one of claims 1 to 7 and claim 10, wherein n is 1 and R2 is a monoglycosyl radical selected from galactosyl and mannosyl.

12. A compound according to any one of claims 1 to 7 and claims 10 to 11, wherein n is 1 and A is -(OCH2CH2). n - and R2 is galactosyl.

13. Compound, according to any of the preceding claims 1 to 7 and claims 10 to 11, wherein n is 1, A is -(SCH2CH2) n - and R2 is mannosyl.

14. Compound according to any of claims 1 to 13, wherein X and Y are CH, or X is N and Y is CH.

15. Compound according to any of the preceding claims comprising a structure selected from:

16. Compound, according to any of claims 1 to 15 above, wherein the counterion W is selected from: halide, acetate, besylate, benzoate, carbonate, bicarbonate, benzenesulfonate, bitartrate, citrate, stearate, phosphate, fumarate, gluconate, glycolate, hexanoate, hydroxynaphthoate, lactate, mesylate, nitrate, nitrite, octanoate, oleate, pamoate, pantothenate, propionate, polygalacturonate, salicylate, succinate, sulfate, tartrate, theoclate, tosylate, triflate, tetraphenylborate, and trifluoroacetate.

17. Compound according to any one of claims 1 to 16, wherein the counterion W is trifluoroacetate.

18. Compound as described in any one of the preceding claims 1 to 17, for use as a medicament.

19. Compound for use, according to claim 18, in the treatment and / or prevention of infections caused by bacteria and / or parasites.

20. Compound for use, according to claim 19, wherein the bacteria are Gram-positive.

21. Compound for use according to claim 20, wherein the bacteria are selected from Corynebacterium amycolatum HUSC 256285, Corynebacterium jeikeium HUSC 223612, Corynebacterium urealiticum HUSC 235888, Fadklamia sp.HUSC 263425, Mycobacterium smegmatis UGRA1, Schaalia radingae HUSC 256790, Staphylococcus aureus HUSC 263091, and Staphylococcus epidermidis HUSC 258042.

22. A compound for use according to claim 19, wherein the parasites are of the family Trypanosomatida.

23. A compound for use according to claim 22, wherein the parasites are of the genera Trypanosoma and Leishmania.

24. A compound for use according to claim 23 for the treatment and prevention of sleeping sickness, Chagas disease, or leishmaniasis.

25. A pharmaceutical composition comprising a compound described in any one of claims 1 to 17, together with a pharmaceutically acceptable excipient and / or vehicle.

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