FR3026102A1 - AMINO-PYRIDINE / PYRIDINIUM ACID CONJUGATES AND THEIR USES AS BIOCIDAL AGENTS - Google Patents

Abstract

The present invention relates to the uses of compounds which are amino acid-pyridine / pyridinium conjugates having biocidal properties, and novel amine-pyridine / pyrimidinic acid conjugate compounds.

Description

Field of the Invention The present invention relates to the uses of compounds which are amino acid-pyridine / pyridinium conjugates having biocidal properties, and novel amino acid-pyridine / pyridinium conjugates.

Background of the Invention Any immersed object is susceptible to a phenomenon known as soiling and defined as the deposition or development of living micro- or macro-organisms. There are, for example, around 25,000 marine species that can settle and colonize submerged surfaces in the marine environment. The most common are bacteria, micro-algae, algae (green or brown) and marine invertebrates: bryozoans, molluscs (barnacles), sea squirts or sponges. This phenomenon consists of several successive steps: adsorption of organic molecules and formation of a "primary film", adhesion of bacteria on the "primary film", development and growth of successive layers of bacterial colonies and formation of a "biofilm" , fixation and development of eukaryotic cells, then of larvae, and finally, after metamorphosis, of sessile organisms which occupy very quickly the totality of the available surface. The consequences of this phenomenon are both economic (rapid corrosion and increased weight of colonized surfaces, overconsumption in fuel, maintenance costs) and ecological (increase of greenhouse gas emissions, introduction of new species, increase of toxic discharges). In order to prevent this phenomenon, different strategies have been put in place, the most common being the use of antifouling paints. These paints include compounds with biocidal properties, the most effective and widespread of which are Tributyl Etheoxide (TBTO) and its derivatives. These compounds were banned in 2008 because they are very toxic, especially for non-target organisms, and not biodegradable. They have been replaced by mixtures of inorganic biocidal agents (for example copper-based) and organic biocidal compounds, mainly herbicides and pesticides, which are also non-biodegradable. Inorganic compounds are effective only at high concentrations (about 10 μg / L) and the impact of organic compounds on marine life is not known and considered a concern by the European Commission.

It would therefore be useful to find compounds that can be used at low levels, to inhibit the proliferation of a living organism efficiently while being environmentally friendly (biodegradability). For the purposes of the present invention, a living organism is a pest for the environment surrounding it. A living organism is, for example, a bacterium, an alga, a micro-alga, a barnacle, a barnacle, an ascidian, a shellfish, a bryophyte, a hydrozoan, a mushroom. Surprisingly, the Applicant has found compounds that meet these needs. Indeed, these compounds are amino acid-pyridine / pyridinium conjugates. They are biodegradable. They also have biocidal properties that allow them to inhibit the proliferation of a living organism for a Minimum Inhibitory Concentration (hereinafter CMI) of 0.001 parts per million to 10 parts per million (denoted hereinafter ppm). Thus, according to a first aspect, the subject of the invention is the use of a compound represented by the following Formula 1: ## STR1 ## Wherein R 1 is oxygen, hydrogen, optionally substituted alkyl, optionally substituted alkenyl, aryl, heterocycloalkyl, heteroaryl, heterocycloalkyl or heteroaryl; hydrogen, alkoxycarbonyl, alkyl, R3 is hydrogen, alkoxycarbonyl, alkyl, R4 is methyl, iso-propyl, sec-butyl, iso-butyl, a group represented by the following formulas: ## STR1 ## where the wavy line indicates the site of attachment, m, n, and p are integers equal to 0 or 1; r is an integer of 1 to 12, preferably selected from 3, 4, 5, 6 and 7; t more preferably still equal to 3; s is an integer selected from 1, 2, 3, 4 and 5, preferably 1 or 2; A- is an ion selected from the group consisting of ci-, cficoo-, CF3SO3, I-, Br-, C104- and mixtures thereof; as a biocidal agent. According to a second aspect, the invention also relates to a compound of Formula I as defined above with the proviso that if: 1) m-0, n-0, pO, r-3, s-2 then R2 is not hydrogen, and 2) m-0, n-0, p0, r-2, s-2, then R2 is not hydrogen. According to a third aspect, the subject of the invention is also a process for obtaining a compound according to the invention comprising the following step: ## STR3 ## in which X is a halogen, for example bromine, chlorine , fluorine, iodine, preferably chlorine. According to a fourth aspect, the subject of the invention is also a composition comprising at least one compound of Formula I or a compound according to the invention or obtained by the process according to the invention and an excipient and / or a solvent. DETAILED DESCRIPTION OF THE INVENTION USE According to a first aspect, the present invention relates to the use of a compound represented by the following Formula I: (R 4) p '/ HO. (R3) n R2. (n + m) A-Formula 1 wherein R 1 is oxygen; a hydrogen; an optionally substituted alkyl group; an optionally substituted alkenyl group; an aryl group; a heterocycloalkyl group; a heteroaryl group; a heterocycloalkylium group or a heteroarylium group; R2 is hydrogen; an alkoxycarbonyl group; an alkyl group; R3 is hydrogen; an alkoxycarbonyl group; an alkyl group; R4 is methyl; iso-propyl; sec-butyl; iso-butyl; a group represented by the following formulas: ## STR2 ## wherein the corrugated line indicates the site of attachment, m, ## EQU1 ## where ## STR2 ## where ## STR2 ## n, and p are integers equal to 0 or 1; r is an integer from 1 to 12, preferably selected from 3, 4, 5, 6 and 7, and more preferably still equal to 3; s is a number integer selected from 1, 2, 3, 4 and 5, preferably 1 or 2; A- is an anion selected from the group consisting of ci-, cficoo-, CF3SO3, r, Br-, C104- and mixtures thereof; As used herein, the term "compound" is intended to mean both the compound as such, its enantiomers, diastereoisomers, hydrates, solvates, crystalline forms and geometrical isomers, tautomers and their pharmaceutically acceptable salts. .

For the purpose of the present invention, the term "alkyl group" denotes a linear or branched hydrocarbyl group of formula C, 1-12, + 1 where z is an integer ranging from 1 to 12. Examples of alkyl group are methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, isopentyl, 2-ethyl-propyl, 1,2-dimethyl-propyl. For the purpose of the present invention, the term "alkenyl group" denotes a linear or branched hydrocarbyl group of formula CyH2y_1 where y is an integer ranging from 2 to 12.

For the purpose of the present invention, the term "optionally substituted alkyl group" denotes an alkyl group or an alkyl group substituted with an alkyl, alkenyl, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, heterocycloalkylium or heteroarylium group. For the purpose of the present invention, the term "optionally substituted alkenyl group" denotes an alkenyl group or an alkenyl group substituted with an alkyl, alkenyl, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, heterocycloalkylium or heteroarylium group. For the purpose of the present invention, the term "aryl group" refers to an aromatic polyunsaturated hydrocarbyl group, having a single ring (ie phenyl) or several contiguous rings (for example naphthyl) or several rings connected by at least one ring a covalent bond (for example biphenyl, fluorenyl), which typically contain 5 to 15 carbon atoms, preferably 6 to 10, and wherein at least one ring is aromatic. The aromatic ring may optionally comprise one to two additional rings (ie cycloalkyl, heterocycloalkyl or heteroaryl) contiguous. The term aryl group also includes partially hydrogenated derivatives of the carbocyclic systems described above. The term aryl group also includes the substituted derivatives of the carbocyclic systems described above, the substituents being alkyl, alkenyl, aryl, cycloalkyl, heterocycloalkyl, heteroaryl, heterocycloalkylium, heteroarylium or a nitrogen group, for example NH 2, NO 2, preferably the substituent is NO2. For the purpose of the present invention, the term "cycloalkyl group" refers to a cyclic hydrocarbyl group, unsaturated or saturated, having one or two rings and having 3 to 10 carbon atoms. For the purpose of the present invention, the term "heterocycloalkyl group" refers to a cycloalkyl group in which at least one carbon atom is replaced by an oxygen, nitrogen and / or sulfur atom. For the purposes of the present invention, the term "heterocycloalkylium group" refers to the positively charged conjugated acid of a corresponding heterocycloalkyl group and thus incorporates the characteristics set out above. A heterocycloalkylium group also comprises an anion in such proportions that electroneutrality is respected and selected from the group consisting of CL, cficoo-, cis, -, 1-, Br-, C104- and mixtures thereof. For the purpose of the present invention, the term "heteroaryl group" denotes a ring or two rings contiguous or connected by a covalent bond, comprising 5 to 12 carbon atoms, preferably 6 to 10 carbon atoms, where at least one of the is aromatic and where at least one or more carbon atoms are replaced by oxygen, nitrogen and / or sulfur. The term heteroaryl also includes systems described above having an aryl, cycloalkyl, heteroaryl or heterocycloalkyl group attached. For the purposes of the present invention, the term "heteroarylium group" denotes the positively charged conjugated acid of a corresponding heteroaryl group and therefore incorporates the characteristics listed above. A heteroarylium group also comprises an anion in such proportions that electroneutrality is respected and selected from the group consisting of ci-, cficoo-, CF3SO3, r, Br-, C104- and mixtures thereof. For the purposes of the present invention, the term "alkoxycarbonyl group" denotes a group chosen from groups of the formula -C (O) O-alkyl, of formula -C (O) O-optionally substituted alkyl and of formula -C (0 ) 0-aryl, in which the term alkyl, similar to alkyl, the term optionally substituted alkyl, similar to optionally substituted alkyl group, and the term aryl, similar to aryl group, are as defined above. The alkoxycarbonyl group is chosen from tert-butoxycarbonyl (Boc), benzyloxycarbonyl and 9-fluorenylmethoxycarbonyl, preferably tert-butoxycarbonyl (Boc). The alkoxycarbonyl group makes it possible to protect the nitrogen atom from the amine function of the amino acid during the synthesis of the compound of the invention, and does not alter the reactivity of said compound with respect to the inhibition. of the proliferation of living organism. For the purposes of the present invention, A- is an anion in such proportions that the compound of Formula I is electronically neutral. The anion A- is selected from the group consisting of CF3C00-, CF3SO3-, 1-, Br-, C104-, and mixtures thereof, preferably the anion A- is hereinafter or cficoo-. The compound of Formula 1 is used as a biocidal agent. For the purpose of the present invention, the term "biocidal agent" refers to a compound having properties enabling it to destroy, repel or render harmless living organisms, in particular enabling it to inhibit the proliferation of a living organism. Without wishing to be bound by any theory, the inventors are of the opinion that the property of inhibition of the proliferation of a living organism by a compound of Formula I results from the inhibition of the growth of said living organism, or of the adhesion of said living organism on one or both surfaces at the same time. The use of the compound of Formula 1 is particularly effective against a living organism selected from the group consisting of a marine bacterium, a terrestrial bacterium, an algae and a microalga, in particular a marine bacterium, a terrestrial bacterium and a microorganism. alga. The marine bacterium may be selected from the group consisting of Halomonas aquamarina, Pseudoalteromonas atlantica, Pseudomonas perfectomarina, Pseudoalteromonas putida, Polaribacter irgensii, Roseobacter litoralis, Shewanella putreficiens, Vibrio harveyi, Vibrio proteolyticus, Vibrio natrie gens, Vibrio aestuarianus, Vibrio carchariae, and their mixtures, in particular Halomonas aquamarina, Polaribacter irgensii, Roseobacter litoralis, Shewanella putreficiens, Vibrio harveyi, Vibrio proteolyticus, Vibrio natriegens, Vibrio aestuarianus, Vibrio carchariae, and mixtures thereof, and more particularly Polaribacter irgensii, Shewanella putrefaciens, and mixtures thereof. The terrestrial bacterium may be selected from the group consisting of Bacillus subtilis, Escherichia Klebsiella pneumonia, Micrococcus luteus, Pseudomonas aeruginosa, Proteus vulgaris, Salmonella typhimurium, Staphylococcus aureus, Streptococcus foecalis, Enterococcus faecium, Acinetobacter baumannii, Enterobacter aerogenes, Enterobacter cloacae, Enterobacter sakazakii, and mixtures thereof, in particular Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and mixtures thereof, and more particularly Staphylococcus aureus, Pseudomonas aeruginosa and their mixture. The microalga may in particular be selected from the group consisting of Cylindrothecca closterium, Halamphora coffeaeformis, Porphyridium purpureum, Exanthemachrysis gayraliae, Pleurochrysis roscoffensis, and mixtures thereof, in particular Cylindrotheca closterium and Halamphora coffeaeformis, and mixtures thereof. The compound of Formula 1 is an amino acid-pyridine / pyridinium conjugate, it is potentially biodegradable, i.e. it can decompose without damaging effect on the surrounding natural environment. Therefore, the use of the compound of Formula 1 can inhibit the proliferation of a living organism, while preserving the surrounding natural environment. Finally, the MIC of the compound of Formula 1 against the proliferation of a living organism ranges from 0.001 ppm to 10 ppm. The compound of Formula 1 can therefore advantageously be used in application on a surface 25 to be treated. Said surface can be made of biological material, metal or plastic, wood, glass, it can also be immersed in the marine environment. Surfaces to be treated are, for example, boat hulls of steel, wood or plastic (polyester composites), glass windows. A biological material surface may be human or animal skin. Owing to its properties (biocide, biodegradability and low MIC), the compound of Formula 1 can advantageously be used as a biocidal agent in a product intended for the field of construction, for example in a paint or varnish, or in an anti-fouling paint. It can also be used as a preservative in a cosmetic product (soaps, creams), or as a disinfectant of equipment, preferably medical equipment, especially equipment surface, or in a detergent (dishwashing liquid). The use of the compound of Formula 1 may be particularly effective in inhibiting the proliferation of living organisms specific to the fouling phenomenon. Thus the use of a compound of Formula 1 makes it possible to inhibit the growth of Cylindrotheca closterium and Halamphora coffeaeformis. The use of the compound of Formula 1 can be as effective in inhibiting the adhesion of Polaribacter irgensii, Shewanella putrefaciens, Staphylococcus aureus and Pseudomonas aeruginosa. The compound of Formula 1 can be used as an antibacterial agent. For the purposes of the present invention, the term "antibacterial agent" refers to a compound having antibacterial properties enabling it to inhibit the proliferation of a bacterium. Without wishing to be bound by any theory, the inventors are of the opinion that the property of inhibiting the proliferation of a bacterium by a compound of Formula I results from the inhibition of the growth of said bacterium, or the adhesion of said bacterium. In addition, the use of the compound of Formula 1 is particularly effective for inhibiting the proliferation of bacteria, and more particularly, for inhibiting the adhesion and growth of the bacteria mentioned above. The compound of Formula 1 may be for use as a medicine. In particular, the compound of Formula I may be for use as an antibiotic in the treatment of a bacterial infection, particularly a bacterial infection caused by Staphylococcus aureus and / or Pseudomonas aeruginosa. Indeed, and advantageously, the use of the compound of formula I may be effective in inhibiting the proliferation of the above-mentioned terrestrial bacteria, in particular Staphylococcus aureus and Pseudomonas aeruginosa. Both of these bacteria are known to be resistant to the biocidal activity of the usual antibiotics. They are also the cause of bacterial infection in humans and animals such as diarrhea, suppurative skin infections, acute myositis, pneumonia, endocarditis, urinary tract infections, phlebitis, certain types of enteritis, meningitis, osteomyelitis, caused by Staphylococcus aureus, nosocomial infections (pulmonary, urinary, gastrointestinal) eye infections, skin infections, respiratory infections, ear infections caused by Pseudomonas aeruginosa.

In a preferred embodiment, a compound of Formula I wherein R2 is hydrogen or alkoxycarbonyl is used. In a preferred embodiment, a compound of Formula I wherein R3 is hydrogen or alkoxycarbonyl is used.

In a preferred embodiment, a compound of Formula I wherein R2 and R3 are hydrogen or alkoxycarbonyl is used. According to a preferred embodiment, a compound of Formula I wherein R 4 is methyl is used; iso-propyl; sec-butyl; iso-butyl; a group represented by the following formulas: ## STR2 ## wherein: ## STR1 ## wherein: ## STR1 ## In particular, the compounds of Formula I as defined above are used with the proviso that if: 1) m -O, n-O, pO, r-3, s-2, then R2 is not hydrogen and 2) m-0, n-0, p0, r-2, s-2, then R2 is not hydrogen. According to a specific embodiment, the compound of Formula I in which m = 0, n = 0, p = 1, r = 3, s = 1, R2 is tert-butoxycarbonyl and R4 is sec-butyl to inhibit proliferation of a micro-alga cited above. In particular the use of this compound of Formula 1 is effective to inhibit the growth and / or adhesion of Halamphora coffeaformis.

According to a specific embodiment, the compound of Formula I in which m = 0, n = 0, p = 0, r = 3, s = 5, and R2 is hydrogen to inhibit the proliferation of a micro-alga. quoted above. In particular the use of this compound of Formula 1 is effective for inhibiting the growth of Cylindrothecca closterium and / or Halamphora coffeaformis. The use of this compound of Formula 1 is also effective in inhibiting the adhesion of Halamphora coffeaformis. Compound of Formula 1 According to a second aspect, the subject of the invention is a compound represented by the following Formula I: ## STR2 ## ## STR2 ## Formula I wherein R 1 is oxygen, hydrogen, an optionally substituted alkyl group, an optionally substituted alkenyl group, an aryl group, a heterocycloalkyl group, a heteroaryl group, a heterocycloalkylium group or a heteroarylium group, R2 is a hydrogen atom. an alkoxycarbonyl group; an alkyl group; R3 is a hydrogen; an alkoxycarbonyl group; an alkyl group; R4 is a methyl; an iso-propyl; a sec-butyl; an iso-butyl; a group represented by the following formulas: SH N H2 Se1-1 OH VVVVV-% / * / * JUV, VVVVY. H2N 0 H2N NOVW. NOVVV, VVVVV, JVVVV-VVVVV-7 7 7 7 7 where the wavy line indicates the fixation site, m, n, and p are integers equal to 0 or 1; r is an integer of 1 to 12, preferably selected from 3, 4, 5, 6, t 7, and more preferably still equal to 3; s is an integer selected from 1, 2, 3, 4 and 5, preferably 1 or 2; A- is an anion selected from the group consisting of ci-, cficoo-, CF3SO3, r, Br-, C104- and mixtures thereof; with the proviso that if: 1) m - 0, n - 0, p - 0, r - 3, s - 2 then R2 is not hydrogen and 2) m - 0, n - 0, p - 0, r - 2, s - 2 then R2 is not hydrogen. According to one embodiment, in Formula 1, if R 1 is an optionally substituted alkyl group or an optionally substituted alkenyl group then r, and z or y have the same value.

Preferably, r is equal to 3 because for this value the synthesis of the compound according to the invention is facilitated and is more economical. According to a preferred embodiment, in Formula 1, R 1 is an alkyl group substituted with a heteroaryl group. Most preferably, said heteroaryl group is pyridine. In a preferred embodiment, in Formula 1, R 1 is an alkyl group substituted with a heteroarylium group. Most preferably, said heteroarylium group is pyridinium and the anion is CF3c00-. In a preferred embodiment, in Formula 1, R2 is hydrogen or alkoxycarbonyl. In a preferred embodiment, in Formula I, R3 is hydrogen or alkoxycarbonyl. In a preferred embodiment, in Formula 1, R2 and R3 are hydrogen or alkoxycarbonyl.

According to a preferred embodiment, in Formula 1, R4 is methyl; iso-propyl; sec-butyl; iso-butyl; a group represented by the following formulas: ## STR2 ## wherein one of the following formulas is: particularly, in Formula 1, R1 is oxygen, hydrogen; alkyl substituted with heteroaryl or heteroarylium, R2 is hydrogen, alkoxycarbonyl, R3 is hydrogen, alkoxycarbonyl and R4 is sec-butyl, a group represented preferred embodiment, in Formula I, R1 is hydrogen, 3-propylpyridine or 3-propylpyridinium, R2 is hydrogen or tert-butoxycarbonyl, R3 is hydrogen and R4 is sec-butyl, a group represented by In particular, the compound according to the invention is selected from the compounds of Table 1 below: Table 1 Compound No. Formula Compound No. Formula 14 ## STR1 ## ## STR5 ## ## STR2 ## ## STR2 ## ## STR8 ## N + CF3C00 + CF3C00 + CF3C00 + CF3C00 + H + 24 O1, NH2 + CF3C00-NH + HO) N + H + CF3C00 Embedded image wherein Boc is tert-butoxycarbonyl group. ## STR5 ## wherein Boc is tert-butoxycarbonyl. More particularly, the compound according to the invention is chosen from the compounds of Table 2 below: Table 2 Compound No. Formula Compound No. Formulas 14 0 N 0 oc Boc NN Boc HO HO N HO 0 17 o \ N 20 HO OF3O00 "H2 + NI NH + HO) L.7N01 OF3O00" Boc 21 CF3C00- - O22O HO). ## STR5 ## ## STR2 ## ## STR5 ## wherein Boc is tert-butoxycarbonyl These compounds are the least expensive and most readily available compounds. synthesizable compounds of Formula 1, because the length of the alkyl chain, represented by r, is short (r is equal to 3.) Moreover, they are particularly effective in inhibiting the proliferation of a bacterium, marine and terrestrial, d algae and microalgae, and more particularly, to inhibit the adhesion of marine and terrestrial bacteria and the growth of microalgae mentioned above The compound according to the invention may be intended to be used as a medicament In particular, it can be used as an antibiotic and can thus be used for the treatment of a bacterial infection. e, in particular bacterial infection caused by Staphylococcus aureus, Pseudomonas aeruginosa and their mixture. The infections caused by Staphylococcus aureus, Pseudomonas aeruginosa and their mixture are those mentioned in connection with the use of the compound of Formula 1. According to a third aspect, the invention relates to a process for obtaining a compound according to According to the invention, said method of obtaining comprises the following step: (R4) p (R4), ## STR2 ## Boc Step B1 Boc Boc Wherein X is halogen, for example bromine, chlorine, fluorine, iodine, preferably chlorine, wherein Boc is tert-butoxycarbonyl, and wherein R4, p, r and s are As previously defined, in Step 1, the haloalkylpyridine and the amino acid protected with N-Boc are introduced into a polar aprotic solvent to give the compound of formula B1 in the form of an oil. solubilize the different reagents involved in the reactions of Step 1 of the process according to The polar aprotic solvents which can be used are dichloromethane, tetrahydrofuran, dimethylformamide, dimethylsulfoxide, especially dichloromethane and dimethylformamide are preferred. According to one embodiment in which R1 is an oxygen, the process for obtaining a compound according to the invention further comprises a step of oxidation of compound Bi. In this oxidation step, the compound Bi, previously solubilized in a solvent, is mixed with an oxidant. The solvents that can be used are dichloromethane, tetrahydrofuran, dimethylformamide, dimethylsulfoxide, acetic acid, especially dichloromethane is preferred. The oxidants that can be used are dimethyldioxirane (DMD), hydrogen peroxide and metachloroperbenzoic acid (mCPBA), which is particularly suitable as oxidant.

According to one embodiment in which R 1 is a hydrogen, the process for obtaining a compound according to the invention further comprises the following step: (R 4) p (R 4) p H 0 N B 1 0 Bac I HO Step 2 B2 o N / H2 + 1 "% NH ±. Wherein Boc is tert-butoxycarbonyl, and wherein R4, A, p, r and s are as defined above.

In Step 2, the compound of formula B1 is introduced into an acid-containing solvent, resulting in the compound of formula B2 being obtained. The acids that can be used are trifluoroacetic acid, trifluoromethanesulfonic acid, hydrochloric acid, hydrobromic acid, trifluoroacetic acid is particularly suitable as acid. According to an embodiment wherein R2 and / or R3 is alkyl, the process for obtaining a compound comprises, in addition to Step 2, an optional alkylation step. During the optional alkylation step, the compound of formula B2 is introduced into a solvent in the presence of a base and an alkyl halide, which leads to the production of a compound in which R2 and / or or R3 is alkyl. The solvents which can be used are dimethylformamide (DMF), tetrahydrofuran (THF), dichloromethane, butanol, dimethylsulfoxide (DMSO), acetonitrile, in particular DMF. The bases that can be used are diisopropylethylamine (DIEA), triethylamine (TEA), sodium hydride (NaH), lithium hydride (LiH), potassium hydride (KH), sodium carbonate (Na2CO3), potassium carbon (K2CO3), cesium carbon (Cs2CO3), especially DIEA.

According to one embodiment in which R1 is not hydrogen, the process for obtaining a compound according to the invention may comprise, in addition to Step 1, the following steps: (R4) p HO N HO ## STR3 ## Step B ## STR2 ## in which Boc is the tert-butoxycarbonyl group, in which R1 is an optionally substituted alkyl group; an optionally substituted alkenyl group; a heterocycloalkyl group; a heteroaryl group, and wherein R4, A, p, r and s are as defined above. In Step 3, the compound of formula B1 is introduced with 1-chloro-2,4-dinitrobenzene in a polar protic solvent to obtain the compound of formula B3 as an oil. The polar protic solvents which can be used are water, methanol, ethanol, propanol, butan-1-ol, in particular methanol. In Step 4, the compound of formula B3 reacts with R1-NH2 in a polar protic solvent to give the compound of formula B4. The polar protic solvents which can be used are water, methanol, ethanol, propanol, butan-1-ol, in particular butan-1-ol. According to the embodiment in which R 1 is not hydrogen, the process for obtaining a compound according to the invention may further comprise the following step: embedded image in which Boc is the tert-butoxycarbonyl group, wherein R 1 is a heterocycloalkyl group or a heteroarylium group, and wherein R 4, A, p, r and s are as defined above.

In Step 5, the compound of formula B4 is introduced into an acidic solvent, resulting in the compound of formula B5 being obtained. The acidic solvents that can be used are trifluoroacetic acid, trifluoroacetic acid is particularly suitable as an acidic solvent. According to an embodiment wherein R2 and / or R3 is alkyl, the process for obtaining a compound comprises, in addition to Step 5, an optional alkylation step.

During the optional alkylation step, the compound of formula B5 is introduced into a solvent in the presence of a base and an alkyl halide at reflux, which leads to the production of a compound in which R2 and / or R3 is alkyl. The solvents which can be used are dimethylformamide (DMF), tetrahydrofuran (THF), dichloromethane, butanol, dimethylsulfoxide (DMSO), acetonitrile, in particular DMF. The bases that can be used are diisopropylethylamine (DIEA), triethylamine (TEA), sodium hydride (NaH), lithium hydride (LiH), potassium hydride (KH), sodium carbonate (Na2CO3), potassium carbon (K2CO3), cesium carbon (Cs2CO3), especially DIEA. The starting materials (haloalkylpyridine and amino acid protected by N-Boc) used in the process for preparing the compounds of the present invention are generally available from commercial suppliers, such as Sigma-Aldrich, VWR, Bachem. The haloalkylpyridine may also be prepared by the method described in Scheme A below: for example bromine, chlorine, fluorine, iodine, preferably chlorine, and wherein r is as defined above. In Step i of Scheme A, an alkyldiol and tetrabutylammonium bromide are introduced into an aqueous solution of hydrobromic acid. The mixture is heated to give the bromoalcohol. Any heating techniques used in synthetic processes in organic chemistry can be used, in particular microwave heating is preferred.

In Step ii of Scheme A, the bromoalcohol, dihydro-2H-pyran and pyridinium p-toluenesulfonate are introduced into a polar aprotic solvent which leads to the formation of bromotetrahydropyran-2-yloxyalkane. The polar aprotic solvent makes it possible to solubilize the various reagents involved in the reactions of Step ii of scheme A. The polar aprotic solvents which can be used are dichloromethane, tetrahydrofuran, dimethylformamide, dimethylsulfoxide, in particular dichloromethane is preferred. In Step iii of Scheme A, diisopropylamine (713r2NH), n-butyllithium (n-BuLi), and 1,3-dimethyl-3,4,5,6-tetrahydro-2 (1H) -pyrimidinone ( DMPU) are first introduced into a polar aprotic solvent. The bromotetrahydropyran-2-yloxyalkane is then added to this mixture to give the compound of formula Cl. The polar aprotic solvent makes it possible to solubilize the various reagents involved in the reactions of Step iii of scheme A. The aprotic polar solvents which can be used are dichloromethane, tetrahydrofuran, dimethylformamide, dimethylsulfoxide, especially tetrahydrofuran is preferred. In Step iv of Scheme A, the compound of formula Cl is introduced into a polar protic solvent. An acidic aqueous solution is then added which leads to obtaining a hydroxyalkylpyridine. The polar protic solvents that can be used are water, methanol, ethanol, propanol, butan-1-ol, especially methanol is preferred. The aqueous acid solution may be an aqueous solution of hydrochloric acid, nitric acid, sulfuric acid, acetic acid and mixtures thereof, in particular hydrochloric acid is preferred.

In Step v of Scheme A, the hydroxyalkylpyridine is introduced into an ether solution. A halogenated compound is then added to give the haloalkylpyridine. Useful ethers are the isomers of dioxane. Halogenated compounds are thionyl halides, such as thionyl bromide, thionyl chloride, thionyl fluoride, thionyl iodide, preferably thionyl chloride.

The compound obtained by the process according to the invention may be intended for use as a medicament. In particular, it can be used as an antibiotic. It can thus be used for the treatment of a bacterial infection, in particular a bacterial infection caused by Staphylococcus aureus, Pseudomonas aeruginosa and their mixture. The infections caused by Staphylococcus aureus, Pseudomonas aeruginosa and their mixture are those mentioned in connection with the use of the compound of Formula 1. Composition According to a fourth aspect, the invention relates to a composition comprising at least one compound of Formula 1, or to less a compound according to the invention, or obtained by the process of the invention and an excipient and / or a solvent.

The composition comprises an effective concentration of a compound (i.e. active substance) according to the invention, or obtained by the method of the invention and also has biocidal properties. It can inhibit the proliferation of a living organism. In particular, the composition can inhibit the growth of a living organism and inhibit the adhesion of a living organism to a surface. Said surface is advantageously such as that described above in connection with the use of the compound of Formula 1. A living organism whose proliferation can be inhibited by the composition according to the invention is advantageously such as that described above in connection with the use of the compound of Formula 1. The presence of a single compound of Formula I or a single compound according to the invention, or obtained by the process of the invention, is sufficient for the composition according to the invention to have the properties previously mentioned. A composition comprising a combination of compounds of Formula I and / or compounds according to the invention and / or obtained by the process of the invention also has the properties mentioned above. Such an association can advantageously lead to synergistic effects between the compounds, such as, for example, reducing the MIC of said composition, reinforcing and / or broadening the spectrum of living organisms whose proliferation is inhibited. According to one embodiment, the composition may be in solid form or in liquid form.

When the composition is in solid form, it does not include any other biocidal compound. When the composition is in liquid form, it further comprises a stabilizer, an adjuvant. The stabilizer may be a compound of Formula 1 because of its role as a preservative. According to a preferred embodiment, the composition according to the invention is an antifouling paint. Indeed, the composition according to the invention is particularly effective in inhibiting the proliferation of organisms living in a marine environment. Thus, the composition makes it possible to effectively inhibit the adhesion of bacteria and the growth of the microalgae described above on submerged surfaces in a marine environment, for example hulls of ships, oil rigs, tubes, piles. , pipelines, heat exchangers. The composition is also effective in inhibiting the growth of said living marine organisms.

EXAMPLES Example 1 Synthesis of Compounds In the following examples of synthesis, the term "eq." the word "equivalent". Example 1a Synthesis of the Haloalkylpyridine Precursor: 3-chloroalkylpyridine Synthesis of 6-Bromohexyl-1-ol (Compound 1) and 12-Bromododecan-1-ol (Compound 2) BrOH 1: r = 6 2: r = 12 In a aqueous solution of 48% bromohydric acid (1) are introduced, 1 alkyldiol of formula HO OH (r = 6 or r = 12) and 0.2 eq. of tetrabutylammonium bromide. The mixture is subjected to microwaves for 10 minutes and then taken up in 15 ml of dichloromethane. The solution obtained is then washed successively with 20 ml of a saturated aqueous sodium carbonate solution, then with 20 ml of water and finally 20 ml of a saturated aqueous sodium chloride solution. The organic phase is dried over magnesium sulfate and the solvent is evaporated under reduced pressure to give a pale yellow oil. Finally, the residue obtained is purified by liquid chromatography on silica gel (eluent: Cyclohexane-AcOEt: 30:70) to give the bromoalcohol (Compound 1 or Compound 2) in the form of a colorless oil. C6H13BrO (Compound 1) Yield 50 Rf 0.41 (Cyclohexane / AcOEt; 3: 7 v / v) 11I NMR (200 MHz, CDCl3) δ 3.65 (t, J = 6.4, 2H, H6 ), 3.41 (t, J = 6.8, 2H, H1), 1.85 (quint, J = 6.8, 2H, H5), 1.56 (quint, J = 6.7, 2H, H2), 1.43 (m, 4H, H4, H3). 13C N1VIR (50 MHz, CDCl3) δ 62.9 (Cl), 33.9 (C6), 32.8 (C5), 32.6 (C2), 28.1 (C4), 25.7 (C3) .

MS-ESI (pos) [M + H] m / z 181.1. C12H25BrO (Compound 2) Yield 60 Rf 0.52 (Cyclohexane / AcOEt; 7: 3 v / v) 11I NMR (200 MHz, CDCl3) δ 3.63 (t, J = 6.6, 2H, H12 ), 3.38 (t, J = 6.8, 2H, H1), 1.56 (m, 4H, H11, H2), 1.27 (m, 16H, H10-H3). 13C NMR (50 MHz, CDCl3)? 63.2 (Cl), 32.9 (C12), 29.9 (C11), 29.7 (C2), 29.7 (C5, C4), 29.6 (? C6), 29.6 (C7), 26.3 (C8), 25.9 (C9), 20.9 (C10), 14.2 (C3). MS-ESI (pos) [M + H] m / z 265.4. 1-Bromo-5-tetrahydropyran-2-yloxy pentane (Compound 3) and 1-Bromo-11-tetrahydropyran-2-yloxyundecane (Compound 4) BrOO 3: r = 6 4: r = 12 In 15 mL of anhydrous dichloromethane are introduced, 1 eq. bromoalcohol, 1.5 eq. 3,4-dihydro-2H-pyran and 0.1 eq. pyridinium p-toluenesulfonate. The mixture is stirred at ambient temperature for 18 hours. The organic phase is washed with 100 ml of an aqueous solution of sodium carbonate (2M) and then dried over magnesium sulphate. After filtration, the solvent is evaporated under reduced pressure to yield a pale yellow oil. Finally, the residue obtained is purified by liquid chromatography on silica gel (cyclohexane-AcOEt: 3: 7) to yield bromotetrahydropyran-2-yloxyalkane (Compound 3 or Compound 4) in the form of a colorless oil. Ci iH2iBrO2 (Compound 3) yield. 100 Rf 0.84 (Cyclohexane / AcOEt; 3: 7, v / v) 11I NMR (200 MHz, CDCl3) δ 4.58-4.55 (m, 1H, He), 3.91-3.68 ( m, 2H, Ha), 3.57-3.44 (m, 2H, H6), 3.41-3.32 (m, 2H, H1), 1.94-1.80 (m, 1H, H5). ), 1.80-1.66 (m, 2H, Hd), 1.64-1.51 (m, 6H, H 2, Hb, Hc), 1.47-1.36 (m, 4H, H 4, H3). 13C NMR (50 MHz, CDCl3)? 99.0 (Ce), 67.7 (Ca), 62.5 (C1), 33.1 (C6), 31.2 (C5), 30.9 (Cd) , 29.8 (C2), 29.3 (C3), 29.2 (C3), 26.3 (Cb), 25.6 (C4), 19.9 (Cc). MS-ESI (pos) [M + H] m / z 265.5.

C17H33BrO2 (Compound 4) Yield: 100 Rf 0.83 (Cyclohexane / AcOEt; 4: 6; v / v) 11I NMR (200 MHz, CDCl3) δ 4.58-4.55 (m, 1H, He), 3.92-3.67 (m, 2H, Ha), 3.54-3.44 (m, 2H, H6), 3.44-3.35 (m, 2H, H1), 1.92-1. , 77 (m, 4H, H11, Hd), 1.70-1.59 (m, 4H, Hb, Hc), 1.55-1.54 (m, 4H, H3, H2), 1.26 (m.p. m, 14H, H10-4). 13C NMR (50 MHz, CDCl3)? 99.0 (Ce), 67.5 (Ca), 62.5 (C1), 34.1 (C12), 32.9 (C11), 30.9 (Cd) , 29.8 (C2), 29.7 (C3), 28.1 (C10), 25.6 (Cb, C9-C4), 19.8 (Cc). MS-ESI (pos) [M + H] m / z 349.6.

Compounds Cl: 3- (12-tetrahydropyran-2-yloxydodecyl) pyridine (Compound 5) and 3- (6-tetrahydropyran-2-yloxyhexyl) pyridine (Compound 6) 5: r = 7 6: r = 13 In 20 mL of anhydrous tetrahydrofuran, previously cooled to 0 ° C., are introduced, 10 eq. of / Pr2NH then dropwise 10 eq. n-BuLi (1.6M in hexane). The pale yellow solution obtained is maintained at 0 ° C. for 30 min and then 10 eq. of DMPU. The solution is stirred at 0 ° C for another 20 min, then a solution of methylpyridine in anhydrous tetrahydrofuran (10 mL) is introduced for 10 min. After 30 min at 0 ° C., the red solution obtained is cooled to -78 ° C. and 1 eq. bromotetrahydropyran-2-yloxyalkane (Compound 3 or Compound 4) is added for 10 min. The mixture obtained is stirred for 1 hour at -78 ° C. and then gradually brought to room temperature. The solution is stirred for 18 hours and then are introduced 50 ml of a saturated aqueous ammonium chloride solution and 50 ml of water. The two phases obtained are separated and the aqueous phase is extracted with ethyl acetate (3 × 100 mL). The combined organic phases are dried over anhydrous magnesium sulphate, filtered and concentrated under reduced pressure. The yellow residue obtained is purified by liquid chromatography on silica gel (Cyclohexane-AcOEt: 3: 7) to yield 3- (12-tetrahydropyran-2-yloxydodecyl) pyridine (Compound 5) and 3- (6-tetrahydropyran-2) -yloxyhexyl) pyridine (Compound 6) as a yellow oil.

C17H27NO2 (Compound 5) yield 48 Rf 0.59 (Cyclohexane / AcOEt; 3: 7, v / v) 11I NMR (200 MHz, CDCl3) δ 8.43 (s, 2H, H2 ', H6'), 7.48 (td, J = 7.8-1.8, 1H, H4 '), 7.18 (dd, J = 7.8-4.8, 1H, H5'), 4.56 (dde, J = 4.4-3, 1H, He), 3.91-3.66 (m, 2H, H), 3.54-3.31 (m, 2H, H1), 2.59 (t, 2H); , J = 7.2, H7), 1.84-1.75 (m, 2H, Hd), 1.64-1.53 (m, 8H, H6, H3, H3 Hc, Hb), 1.34 (m, 6H, H5, H4). 13C NMR (50 MHz, CDCl3)? 150.0 (C2 '), 147.3 (C6'), 138.0 (C3 '), 135.9 (C4'), 123.4 (C5 '), 98 , 9 (Ce), 67.6 (Ca), 62.4 (Cl), 32.9 (C7), 30.9 (Cd), 30.8 (C2), 29.7 (C6), 29, 2 (C5), 29.0 (C4), 26.1 (C3), 25.5 (Cb), 19.7 (Cc). MS-ESI (pos) [M + H] m / z 278.4. C23H39NO2 (Compound 6) yield. Rf 0.52 (Cyclohexane / AcOEt; 4: 6; v / v) 11I NMR (200 MHz, CDCl3) δ 8.42 (dd, 2H, J = 1.6-4.6, H6 ', H2' ), 7.48 (td, J = 6-1.8, 1H, H4 '), 7.18 (dd, 1H, J = 7-4.8-0.6, H5'), 4.55 ( dde, J = 2.8-4.2, 1H, Ce), 3.91-3.66 (m, 2H, Ha), 3.54-3.31 (m, 2H, H1), 2.59. (t, J = 7.4, 2H, H13), 1.79 (m, 2H, Hd), 1.60-1.52 (m, 8H, H12, H3, He, Hb), 1.27 ( m, 16H, H4-11). 13C NMR (50 MHz, CDCl3)? 150.3 (C2 '), 147.3 (C6'), 135.9 (C4 ', C3'), 123.2 (C5 '), 99.0 (Ce) , 67.9 (Ca), 62.5 (Cl), 33.2 (C13), 31.3, (Cd), 30.9 (C2), 29.9 (C12), 29.6-29, 8 (C10-C4), 29.3 (C11), 26.4 (C3), 25.6 (Cb), 19.9 (Cc). MS-ESI (pos) [M + H] m / z 362.4. 12-pyridin-3-yldodecan-1-ol (Compound 7) and 6-pyridin-3-ylhexan-1-ol (Compound 8) / OH 7: r = 78: r = 13 In 15 ml of MeOH are introduced , 1 eq. 3- (n-tetrahydropyran-2-yloxyalkyl) pyridine (Compound 5 or Compound 6) and 1.1 eq. of an aqueous solution of 3M hydrochloric acid. The mixture is stirred at ambient temperature for 18 hours and then concentrated under reduced pressure. The residue obtained is taken up in ethyl acetate. The organic phase is washed with an aqueous solution of saturated sodium hydrogen carbonate. The aqueous phase is extracted with ethyl acetate (3 x 50 mL). The combined organic phases are dried over magnesium sulphate, filtered and concentrated under reduced pressure. Finally, the residue obtained is purified by liquid chromatography on silica gel (Cyclohexane-AcOEt: 3: 7) to yield pyridin-3-yldodecan-1-ol (Compound 8) in the form of white crystals and 6-pyridinic acid. 3-ylhexan-lol (Compound 7) as a colorless oil.

C12H19NO (Compound 7) Yield: Rf 0.42 (Cyclohexane / AcOEt; 5: 5 v / v) 11I NMR (200 MHz, CDCl3) δ 8.42 (s, 2H, H6 ', H2'), 7.48 (td, J = 7.8-1.8, 1H, H4 '), 7.19 (dd, J = 7.6-4.8, 1H, H5'), 3.63 (t, J = 6.4, 2H, H1), 2.59 (t, J = 7.2, 2H, H7), 1.68-1.52 (m, 4H, H6-H2), 1.34 (se, 6H). , H5-H3). 13C NMR (50 MHz, CDCl3)? 150.0 (C2 '), 147.2 (C6'), 138.0 (C3 '), 135.9 (C4'), 123.4 (C5 '), 63 , 0 (Cl), 33.1 (C7), 32.8 (C2), 31.2 (C6), 29.3 (C5), 29.2 (C4), 25.8 (C3). MS-ESI (pos) [M + H] m / z 194.2. C18H31NO (Compound 8) yield. Rf 0.47 (Cyclohexane / AcOEt; 5: 5 v / v) 11I NMR (200 MHz, CDCl3) δ 8.42 (dd, J = 4.6-1.4, 2H, H6 ', H2' ), 7.48 (dt, J = 2-7.6, 1H, H4 '), 7.19 (ddd, J = 7.6-4.8-0.6, 1H, H5'), 3, 63 (t, J = 6.6, 2H, H1), 2.59 (t, J = 7.4, 2H, H13), 1.56 (m, 4H, H12, H2), 1.28 (seq. , 14H, H11-H3). 13C NMR (50 MHz, CDCl3)? 150.0 (C2 '), 147.1 (C6'), 138.1 (C3 '), 135.3 (C4'), 123.4 (C5 '), 63 , 1 (Cl), 33.1 (C13), 32.9 (C2), 31.2 (C12), 29.2-29.7 (C11-C4), 25.9 (C3). MS-ESI (pos) [M + H] m / z 278.7. 3- (3-chloropropyl) pyridine (Compound 9), 3- (6-chlorohexyl) pyridine (Compound 10) and 3- (12-chlorododecyl) pyridine (Compound 11) Cl 9: r = 3 10: r = 7 11 In 15 ml of dioxane, previously cooled to 0 ° C., 1 eq. n-Pyridin-3-ylalkan-1-ol (Compound 7 or Compound 8 or 3-hydroxypropanpyridine) and then dropwise 1.2 eq. of thionyl chloride for 10 min. The mixture is stirred at ambient temperature for 18 hours and then 15 ml of ethanol are added. The mixture obtained is refluxed for 5 minutes. The solution is filtered hot. The cooled filtrate is evaporated under reduced pressure. The residue obtained is purified by liquid chromatography on silica gel (CyclohexaneAcOEt: 3: 7) to yield 3- (n-alkyl) pyridinium chloride (Compounds 9, 10, 11) in the form of a yellow oil. C8H10ClN (Compound 9, obtained from 3-hydroxypropanpyridine) Yield 90 Rf 0.40 (Cyclohexane / AcOEt 3: 7 v / v) 11I NMR (200 MHz, CDCl3) δ 8.48 (se, 2H) H6 ', H2'), 7.50-7.56 (dt, 1H, H4 '), 7.20-7.26 (dd, J = 7.8-2.8, 1H, H5'), 3.54 (t, J = 6.4, 2H, H1), 2.80 (t, J = 7.2H, H3), 2.02-2.17 (m, 2H, H2). 13C NMR (50 MHz, CDCl3) δ 148.7 (C2 '), 146.3 (C6'), 138.0 (C3 '), 135.7 (C4'), 121.5 (C5 '), 44 , 3 (C1), 32.7 (C3) 28.8 (C2). MS-ESI (pos) [M + H] m / z 156.1. C12H18ClN (Compound 10, obtained from Compound 7) yield. Rf 0.51 (Cyclohexane / AcOEt; 7: 3; v / v) 11I NMR (200 MHz, CDCl3) δ 8.44 (se, 2H, H6 ', H2'), 7.50 (td, J = 7.8-1.8, 1H, H4 '), 7.21 (dd, J = 4.8-7.8, 1H, H5'), 3.52 (t, J = 7.8, 2H, H1), 2.61 (t, J = 7.8, 2H, H7), 1.83-1.69 (m, 2H, H6), 1.65-1.55 (m, 2H, H2), 1.41-1.28 (m, 6H, H5-H3). 13C NMR (50 MHz, CDCl3) δ 149.7 (C2 '), 147.1 (C6'), 138.1 (C3 '), 136.2 (C4'), 123.5 (C5 '), 45 , 2 (Cl), 33.1 (C7), 32.7 (C6), 31.1 (C2), 29.1 (C5), 28.8 (C4), 26.9 (C3). MS-ESI (pos) [M + H] m / z 212.1. C18H30ClN (Compound 11, obtained from Compound 8) yield. Rf 0.67 (Cyclohexane / AcOEt; 3: 7, v / v) 11I NMR (200 MHz, CDCl3) δ 8.44 (se, 2H, H6 ', H2'), 7.48 (td, J = 7.6-2, 1H, H4 '), 7.19 (dd, J = 4.6-7.6, 1H, H5'), 3.53 (t, J = 6.6, 2H, H1), 2 , 60 (t, J = 7.4, 2H, H13), 1.83-1.76 (m, 2H, H12), 1.64-1.53 (m, 2H, H2), 1.44- 1.30 (m, 4H, H11, H3), 1.25 (se, 14H, H10-H4). 13C NMR (50 MHz, CDCl3) δ 149.9 (C2 '), 147.1 (C6'), 138.1 (C3 '), 135.9 (C4'), 123.4 (C5 '), 45 , 3 (Cl), 36.6 (C13), 33.1 (C12), 32.7 (C2), 29.2-31.5 (C10-05), 28.9 (C4), 26.9 (C3). MS-ESI (pos) [M + H] m / z 296.3.

Example 1b: Synthesis of the compound of Formula B1: (R4) p HO In 15 ml of dimethylformamide, 1.1 eq. sodium iodide and 1 eq. 3-chloroalkylpyridine (Compound 9 or Compound 10). In parallel, 1.1 eq. of potassium carbonate and 1 eq. amino acid protected by N-Boc (Phe, Met, Ile, Ahx) are solubilized in dimethylformamide. After stirring for 5 minutes, the two solutions are mixed and refluxed for 18 hours and the solvent is then evaporated off under reduced pressure. Finally, the residue obtained is purified by liquid chromatography on silica gel (Cyclohexane-AcOEt: 3: 7) to give 3- (3 - ((tert-butoxycarbonyl) (carboxyalkyl) amino) alkyl) pyridine (Compounds 14-). 19 of Formula B1) as a yellow oil. Compound 14 (obtained from Compound 9): Formula B1 in which p = 1, r = 3, s = 1, and Compound 15 (obtained from Compound 9): Formula B1 in which p = 1, r = 3 , s = 1, and R4 = sec-butyl; Compound 16 (obtained from Compound 9): Formula B1 in which p = 1, r = 3, s = 1, and R4 = Compound 17 (obtained from Compound 9): Formula B1 in which p = 0, r = 7, s = 1; Compound 18 (obtained from Compound 10): Formula B1 in which p = 0, r = 3, s = 5; Compound 19 (obtained from Compound 9): Formula B1 in which p = 0, r = 3, s = 1; C22H28N2O4 (Compound 14) Yield Rf 0.58 (Cyclohexane / AcOEt; 4: 6; v / v) [a] 25D -11.0 (c 0.01, MeOH) 111 NMR (200 MHz, CDCl3) 8.47-8.42 (m, 2H, H6 ', H2'), 7.47 (td, 1H, J = 7.6-2, H4 '), 7.30-7.25 (m, 2H, Hk, Hi), 7.23-7.12 (m, 1H, H5 ', H1, H1, Hh), 4.10 (td, J = 6.4-2, 2H, Hc), 4, 57 (dd, J = 8, 1H, Hb), 3.08 (from, J = 6.4, 2H, H1), 2.60 (t, J = 7.2, 2H, H3), 1.97 -1.82 (m, 2H, H2), 1.43 (s, 9H, Hf). 13C NMR (50 MHz, CDCl3) δ 172.2 (Ca), 155.3 (Cd), 150.0 (C2 '), 147.7 (C6'), 136.4 (C3 '), 136.1 (C4 '), 135.9 (Cg), 129.4-120.5 (C5', Ch, Cl, Cj, Ck, Cl), 80.1 (Ce), 64.4 (Cb), 38, 7 (C1), 29.8 (Cc), 29.3 (C3), 28.5 (Cf, Cc). HR1VIS: C22H29N2O4 to 385.2121 (A = 1.28 ppm). C19H30N2O4 (Compound 15) Yield: 90 Rf 0.50 (Cyclohexane / AcOEt; 4: 6; v / v) [Ci] 25D -44.0 (c 0.01, MeOH) 11I NMR (200 MHz, CDCl3) 8.45 (se, 2H, H6 ', H2'), 7.52 (td, J = 8.2, 1.8, 1H, H4 '), 7.22 (dd, J = 7.8). 2.7, 1H, H5 '), 5.03 (d, J = 9, 1H, Hb), 4.15 (t, 2H, J = 6.4, H1), 2.99-2.88 ( m, 2H, H3), 2.70 (t, 2H, J = 8.2, H2), 1.99 (m, 2H, Hh), 1.81 (se, 1H, He), 1.44 (m.p. s, 9H, Hf), 1.05 (t, J = 6.2, 3H, Hg), 0.98 (d, J = 7.8, 3H, Hi). 13C NMR (50 MHz, CDCl3) δ 172.4 (Ca), 150.0 (Cd), 147.8 (C2 '), 147.8 (C6'), 136.4 (C3 '), 135.9 (C4 '), 123.5 (C5'), 79.9 (Ce), 64.1 (Cb), 58.1 (Cl), 38.1 (C3), 30.1 (Cc), 29, (C2), 28.5 (Cf), 25.2 (Ch), 15.7 (Cg), 11.8 (Ci) HR1VIS: C19H31N2O4 to 351.22783 (A = 0.99 ppm).

C181128N204S (Compound 16) Yield 85 Rf 0.39 (Cyclohexane / AcOEt; 3: 7 v / v) [Ci] 25D -64.2 (c 0.02, MeOH) 111 NMR (200 MHz, CDCl3) 8.46 (se, 2H, H6 ', H2'), 7.5 (td, J = 8-2.2, 1H, H4 '), 7.22 (dd, J = 7.8-5, 1H, H5 '), 5.10 (de, J = 9.4, 1H, Hb), 4.18 (td, J = 6.4-1.4, 2H, H1), 2.71 (t, J = 7.4, 2H, H3), 2.55 (t, J = 7.4, 2H), 2.10 (s, 3H, Hh), 1.97-2.06 (m, 2H, m.p. He), 1.83-1.97 (m, 2H, H 2), 1.44 (s, 9H, Hf). 13C NMR (50 MHz, CDCl3) δ 172.5 (Ca), 162.6 (Cd), 149.9 (C2 '), 147.8 (C6'), 136.3 (C3 '), 135.8 (C4 '), 123.5 (C5'), 80.2 (Ce), 64.5 (Cb), 52.9 (Cl), 36.6 (C3), 32.2 (Cg), 31, (Cf, Cc), 28.4 (C2), 15.6 (CH). MS: C18E128N20S to [M + H] 369.2 [M + Na] 391.2 [2M + Na] 759.4 C16H24N2O4 (Compound 17) Yield: 50 Rf 0.26 (Cyclohexane / AcOEt; 3: 7; v / v) 111 NMR (200 MHz, CDCl3) δ 8.46 (se, 2H, H6 ', H2'), 7.50 (td, J = 7.8-2 Hz, 1H, H4 '), 7 , 22 (dd, J = 7.8-5, 1H, H5 '), 5.01 (se, 1H, COOH), 4.12 (t, 2H, J = 6.4, Hc), 3.39 (dd, 2H, J = 6.2-6, H1), 2.70 (t, 2H, J = 8.2, H3), 2.52 (t, 2H, J = 6.2, Hb), 1.97 (m, 2H, H2), 1.43 (s, 9H, Hf). 13C NMR (50 MHz, CDCl3)? 172.5 (Ca), 155.7 (Cd), 149.8 (C2 '), 147.6 (C6'), 135.8 (C4 ', C3'), 123.5 (C5 '), 79.4 (Ce), 63.6 (Cl), 36.1 (Cc), 34.6 (C3), 29.8 (Cb), 29.4 (C2), 28.4 (Cf). HR1VIS: C16H25N2O4 + at 309.1808 (A = -0.12 ppm). C20H32N204 (Compound 19) Yield. 75% Rf 0.74 (Cyclohexane / AcOEt; 3: 7 v / v) 111 NMR (200 MHz, CDCl3) δ 8.43 (se, 2H, H6 ', H2'), 7.49 (td, J) = 7.8-2, 1H, H4 '), 7.21 (dd, J = 5-7.8, 2H, H5'), 4.06 (t, J = 6.6, 2H, He), 3.38 (dd, J = 6.2H, H1), 2.6 (t, J = 7.4, 2H, H7), 2.5 (t, J = 6.0, 2H, Hb), 1 , 74-1.54 (m, 2H, H6-H2), 1.42 (s, 9H, CH3), 1.33 (se, 6H, H5-H3). 13C NMR (50 MHz, CDCl3) δ 172.7 (Ca), 155.8 (Cd), 150.0 (C2 '), 147.2 (C6'), 137.8 (C3 '), 135.9 (C4 '), 123.3 (C5'), 64.8 (Ce), 53.5 (Cl), 36.2 (Cc), 34.7 (C7), 33.0 (C6), 28, 6-31.1 (C405), 28.5 (Cf), 25.9 (C3). HR1VIS: C20F13304N2 at 365.2434 (A = 0.13 ppm). Example 1 Synthesis of the compound of Formula B2: (R4) p HO. (n + m) A- In the case where R1 is oxygen, then in 5 ml of dichloromethane are introduced 1.1 eq. compound 14 and 1.1 eq. of mCPBA. The mixture is stirred for 1 hour then the solvent is evaporated under reduced pressure. Finally, the residue obtained is purified by liquid chromatography on silica gel (dichloromethane-MeOH: 98: 2) to give the N-oxide derivative in the form of a white solid. In the case where R1 is not oxygen, then in 4 mL of trifluoroacetic acid is introduced 1 eq. 3- (3 - ((tert-butoxycarbonyl) (carboxyalkyl) amino) alkyl) pyridine (Compounds 14-19). The mixture is stirred for 18 hours then the solvent is evaporated under reduced pressure. The resulting residue is repeatedly taken up in water and lyophilized to yield 3- (3- ((carboxyalkyl) amino) alkyl) pyridine (Compounds 10-25 of Formula B2). Compound 20 (obtained from Compound 14): Formula B2 in which m = 1, n = 1, p = 1, r = 3, s = 1, A- = CF3C00-, = H, R2 = H, R3 = H, R4 = Compound 21 (obtained from Compound 15): Formula B2 in which m = 1, n = 1, p = 1, r = 3, s = 1, A- = CF3C00-, R1 = H, R2 = H, R3 = H, R4 = sec-butyl; Compound 22 (obtained from Compound 16): Formula B2 in which m = 1, n = 1, p = 1, r = 3, s = 1, A- = CF3C00-, = H, R2 = H, R3 = H, R4 = Compound 23 (obtained from Compound 17): Formula B2 in which m = 1, n = 1, p = 0, r = 10 3, s = 1, A- = CF3C00-, = H, R2 = H, R3 = H; Compound 24 (obtained from Compound 18): Formula B2 in which m = 1, n = 1, p = 0, r = 3, s = 5, A- = CF3C00-, = H, R2 = H, R3 = H; Compound 25 (obtained from Compound 19): Formula B2 in which m = 1, n = 1, p = 0, r = 7, s = 1, A- = CF3C00-, = H, R2 = H, R3 = H; C17H20N2O2 (Compound 20) [C1] 25D +11.6 (c 0.01, MeOH) 111 NMR (200 MHz, CD30D) δ 8.58 (se, 2H, H6 ', H2'), 8.11 (from, J = 8.2, 1h, H4 '), 7.73 (m, 1H, Hi), 7.41-7.24 (m, 5H, H5', H1, Hk, H1, Hh), 4.35 (t, 1H, J = 7.0, Hb), 4.22 (t, J = 5.8, 2H, H1), 3.22 (d, 2H, J = 6.8, Hc), 2, 80 (t, 2H, J = 8.0, 2H, H3), 1.99 (m, 2H, H2). 13C NMR (50 MHz, CD30D) δ 170.2 (Ca), 145.9 (C2 '), 145.2 (C6'), 144.1 (C3 '), 143.4 (C4'), 142 (Cg), 135.5-128.9 (C 5 ', C 1, C 1, Ck, Cl, Ch), 66.2 (Cb), 55.0 (Cl), 37.6 (Cc), , 3 (C3), 29.8 (C2). HRMS: CI7H2102N2 + at 285.1603 (4 = -0.62ppm). C14H22N2O2 (Compound 21) [C1] 25D +6.0 (c 0.01, MeOH) 111 NMR (200 MHz, CD30D) δ 8.74 (se, 2H, H6 ', H2'), 8.45 (d, J = 7.8, 1H, H4 '), 7.97 (se, 1H, H5'), 4.35 (td, J = 6.2-2.4, 2H, H1), 4.06 (d. , 1H, J = 3.8, Hb), 3.00-2.93 (m, 2H, H3), 2.86-2.69 (m, 2H, H2), 2.18-2.08 (m.p. m, 2H, Hh), 2.48-1.99 (m, 2H, Hc), 1.04 (m, 6H, Cl, Cg). 13C NMR (50 MHz, CD30D)? 169.9 (Ca), 146.5 (C2 '), 146.3 (C6'), 143.7 (C3 '), 142.1 (C4'), 125, 7 (C5 '), 66.2 (Cb), 58.3 (C1), 37.8 (Cc), 30.3 (C3), 29.9 (C2), 26.9 (CH), 14, 9 (Cg), 11.8 (Ci). HR1VIS: C14H23N2O2 + at 251.1754 (A = -1.68 ppm). C13H20N2O2S (Compound 22) [ci] 25j +7.0 (c 0.02, MeOH) 11I NMR (200 MHz, CD30D) δ 8.77 (se, 2H, H6 ', H2'), 8.53 (d , J = 7.4, 1H, H4 '), 8.00 (se, 1H, H5'), 4.33 (td, J = 6.0-2.0, 2H, H1), 4.25 ( t, J = 6.2, 1H, Hb), 3.00 (t, J = 8.2, 2H, H3), 2.72 (t, J = 7.2, 2H, Hg), 2.28 -2.14 (m, 4H, H 2, He), 2.11 (s, 3H, Hh). 13C NMR (50 MHz, CD30D) δ 170.4 (Ca), 147.2 (C2 '), 147.2 (C6'), 143.1 (C3 '), 141.4 (C4'), 128, 2 (C5 '), 66.4 (Cb), 52.7 (Cl), 36.9 (C3), 30.7 (Cc), 30.1 (Cg), 29.8 (C2), 14, 9 (Ch). HR1VIS: C13H21N2O2S + at 269.1318 (A = 1.96 ppm) C11H16N2O2 (Compound 23) 11I NMR (200 MHz, CD30D) δ 8.52 (se, 2H, H6 ', H2'), 8.16 (d, 1H, J = 7.4Hz, H4 '), 7.97 (se, 1H, H5'), 4.02 (t, 2H, J = 6.4Hz, He), 3.02 (t, J = 6.4Hz, 2H, H1), 2.75 (t, 2H, J = 8.2 Hz, H3), 2.57 (t, 2H, J = 8.6 Hz, Hb), 1.96-1.82 (m.p. , 2H, H2). 13C NMR (50 MHz, CD30D) δ 172.2 (Ca), 147.3 (C2 '), 147.2 (C6'), 145.1 (C3 '), 141.9 (C4'), 141, 9 (C5 '), 65.3 (Cc), 36.3 (H1), 32.1 (Cb), 30.6 (C3), 30.1 (C2). HR1VIS: C11H17N2O2 209.1287 C14H22N2O2 (Compound 24) 111 NMR (200 MHz, CD30D) δ 8.60 (se, 2H, H6 ', H2'), 8.11 (d, J = 8.0, 1H, H4 '), 7.70 (se, 1H, H5'), 4.12 (t, J = 6.2, 2H, H1), 2.96-2.82 (m, 4H, H3, H1), 2.36 (t, J = 7.2, 2H, Hb), 2.091.95 (m, 2H, H2), 1.71-1.62 (m, 4H, He, Hh), 1.49-1. , 36 (m, 2H, Hg). 13C NMR (50MHz, CD30D) δ 25.4 (Cc), 26.8 (Cg), 28.3 (C2), 30.6 (Ch), 34.5 (C3), 40.5 (Cb) , 61.7 (Cl), 64.5 (Ci), 126.7 (C5 '), 142.7 (C4'), 144.5 (C3 '), 146.6 (C6'), 146.7 (C2 '), 175.2 (Ca).

HR1VIS: C14H23N2O2 + at 251.1759 (A = 0.11 ppm). C15H24N2O2 (Compound 25) 111 NMR (200 MHz, CDCl3) δ 8.43 (se, 2H, H6 ', H2'), 7.49 (td, J = 7.8-2, 1H, H4 '), 7 , 21 (dd, J = 5-7.8, 2H, H5 '), 4.06 (t, J = 6.6, 2H, He), 3.38 (dd, J = 6.2H, H1) , 2.6 (t, J = 7.4, 2H, H7), 2.5 (t, J = 6.0, 2H, Hb), 1.74-1.54 (m, 2H, H6-H2) ), 1.33 (se, 6H, H5-H3). 13C NMR (50 MHz, CDCl3) δ 172.7 (Ca), 155.9 (Cd), 150.0 (C2 '), 147.2 (C6'), 137.9 (C3 '), 135.9 (C4 '), 123.4 (C5'), 53.5 (Cl), 36.2 (Cc), 34.7 (C7), 33.1 (C6), 28.6-31.1 (C4) -05), 25.9 (C3). HR1VIS: C15H2502N2 + at 265.1909 (A = - 0.28 ppm).

Example 1d: Synthesis of the compound of formula B3: (R4) p HO / r 0 Boc N + O, N NO2 In 20 ml of MeOH, 1 eq. pyridine (Compounds 14, 15, 16) and 1 eq. 1-chloro-2,4-dinitrobenzene (1 eq). The mixture is refluxed for 18 hours and then evaporated under reduced pressure. The residue obtained is solubilized in dichloromethane and then extracted with water. The aqueous phase is lyophilized to yield the compound of Formula B3, also named Zincke salt (Compounds 26-28) in the form of an orange oil. After purity control by HPLC, the compound is directly involved in Step 4 of Scheme A. Compound 26 (obtained from Compound 14): Formula B3 in which p = 1, r = 3, s = 1, Compound 27 (obtained from Compound 15): Formula B3 wherein p = 1, r = 3, s = 1, = CL, R4 = sec-butyl; Compound 28 (obtained from Compound 16): Formula B3 wherein p = 1, r = 3, s = 1, = R4 = Example 1e Synthesis of the compound of Formula B4: (R4) p HO / mA-N Boc I N Nm + (R 1) m / / jNH 2 15: r = 3 16: r = 13 r is as defined in the application In n-butanol are introduced, 1.1 eq. 3- (aminoalkyl) pyridine (Compounds 12 and 13) and 1 eq. Zincke salt (Compounds 26-28). Compounds 12 and 13 are obtained from compounds 7 and 8 according to the following sequence of reactions. In 5 ml of dimethylformamide, previously cooled to 0 ° C., 3 eq. of diisopropylphosphorazyde, 1 eq. of N-hydroxyalkylpyridine (Compound 7 or Compound 8) then dropwise 3 eq. 1,8-diazabicyclohexaneundec-7-ene. The mixture is stirred at 0 ° C. for 30 min and then 3 eq. sodium azide. The resulting solution is stirred at 100 ° C for 18 hours and then the cooled mixture is added diethyl ether. The solution obtained is washed with water and a saturated aqueous sodium chloride solution, and then dried over sodium sulfate. The solvents are evaporated under reduced pressure. The residue obtained is purified by liquid chromatography on silica gel (Cyclohexane-AcOEt: 3: 7) to give a 3- (azide-n-alkyl) pyridine.

In 5 ml of ethanol are placed 0.03 eq. palladium on charcoal, 1.1 eq. of di-tert-butyl dicarbonate followed by 3- (azide-n-alkyl) pyridine (1 eq.). The mixture is stirred under a hydrogen atmosphere at room temperature for 18 hours. The solution is filtered on Celite (). The filtrate is evaporated under reduced pressure. The residue obtained is purified by liquid chromatography on silica gel (Cyclohexane-AcOEt: 1: 9). Finally, the compound obtained is deprotected with trifluoroacetic acid to give the pure amine (Compounds 12 and 13) as an orange oil. The resulting solution is refluxed for 18 hours until the red color disappears. The solvent is evaporated under reduced pressure. The resulting residue is purified by liquid chromatography on silica gel to yield the desired product (Compounds 29-30) as a yellow oil. Compound 29 (obtained from Compounds 12 and 26): Formula B4 in which m = 1, p = 1, r = 3, s = 1, K = CL, R1 = 3-propylpyridine, R4 = Compound 30 (obtained at from Compounds 12 and 27): Formula B4 in which m = 1, p = 1, r = 3, s = 1, K = CL, R1 = 3-propylpyridine, R4 = sec-butyl; Compound 31 (obtained from Compounds 12 and 28): Formula B4 in which m = 1, p = 1, r = 3, s = 1, K = CL, R1 = 3-propylpyridine, R4 = C30H38N3O4 + (Compound 29) [Ci] 25 D -0.2 (c 0.003, MeOH) 111 NMR (200 MHz, CD30D) δ 8.94 (m, 2H, H14 ', H13'), 8.89 (se, 1H, H2 '), 8.46 (d, 1H, J = 8.0, H6 '), 8.04 (t, 2H, J = 7.6, H11', H4 '), 7.92 (d, 2H, J = 7; , 8, 2xCHar), 7.70 (d, 1H, CHar), 7.27 (m, 4H, 4xCHar), 4.71 (t, 2H, J = 7.4, H7 '), 4.30 (m.p. t, 1H, J = 9.4, Hb), 4.17 (m, 2H, H1), 2.98 (d, 2H, J = 7.8, H3), 2.85 (m, 4H, H9). ', Hc), 2.03 (m, 4H, H8', H2), 1.40 (s, 9H, Hf). 13C NMR (50 MHz, CDCl3)? 172.0 (Ca), 155.2 (C2 '), 150.0 (C14'), 147.8 (Cd), 136.1 (C6 '), 135.9. (C13 '), 129.4-120.6 (CHar), 80.1 (Ce), 64.4 (C7'), 57.9 (Cb), 36.9 (Cl), 33.4 (C9) 31.5 C3), 29.8 (C8 '), 29.3 (C2), 28.5 (Cf). HRMS: C30113804N3 + at 504.2862 (A = 0.59 ppm). C26H38N3O4S + (Compound 30) [Ci] 25D-68 (c 0.001, MeOH). 111 NMR (200 MHz, CD30D) δ 9.0 (se, 1H, H14 '), 8.92 (te, J = 4.6, 1H, H2'), 8.53 (te, J = 6.4). , 1H, H13 '), 8.07 (te, J = 6.6, 1H, H6'), 7.97-7.27 (m, 8H, H12 ', H1, H5', H4 ') 4.75 (t, J = 6.2, 2H, H7 '), 4.25 (m, 1H, Hb), 3.65 (m, 2H, H1), 3.02 (t, J = 7; , 6, 4H, H9 ', H3), 2.87 (t, J = 8.8, 4H, Hg, Hc), 2.19 (s, 3H, Hh), 2.03 (m, 4H, H8). H 2,), 1.47 (s, 9H, CH 3). 13C NMR (50 MHz, CD30D) δ 174.2 (Ca), 149.6 (C2 '), 149.6 (C14'), 149.5 (Cd), 147.6 (C6 '), 143.9 (C13 '), 139.2 (C10'), 138.9 (C3 '), 125.6-129.1 (C12', C11 ', C5', C4 '), 75.8 (Ce), 70 , 0 (Cb), 60.6 (C7 '), 42.5 (Cl'), 35.4 (C3), 31.9 (C9 '), 28.6-31.2 (C8', C2 ') , Cg, Cc), 26.1 (Cf), 15.6 (CH).

HRMS: C26H3804N3S + at 488.2583 (A = 0.25 ppm). C271140N304 + (Compound 31) [Ci] 25D +6.4 (c 0.02, MeOH) 111 NMR (200 MHz, CDCl3) δ 8.80 (se, 2H, H14 ', H13'), 8.51 (d, 1H) , J = 7.8, CH), 8.0 (t, 1H, J = 6.2, CH), 4.35 (t, 2H, J = 6.6, CH 2), 4.07 (d, 1H, J = 3.6, CH), 2.99 (t, 2H, J = 8.6, CH 2), 2.14 (q, 2H, J = 8, CH 2), 2.06 (m, 1H, CH). ), 1.54 (sep, 1H, J = 6.4, CH 2), 1.43 (sep, 1H, J = 6.4, CH 2), 1.05 (t, 3H, J = 6.2, CH3), 0.98 (d, 3H, J = 7.8, CH3). HRMS: C27H4004N3 + at 470.3018 (A = -0.32 ppm). Example 1f: Synthesis of the compound of Formula B5: (R4) p. (n + m) A- In trifluoroacetic acid are introduced compounds 29-31. The resulting mixture is stirred at room temperature for 4 hours. The solvent is evaporated under reduced pressure. The residue obtained is taken up several times, is solubilized in water (20 mL) and then lyophilized to yield compounds 32-34.

Compound 32 (obtained from Compound 29): Formula B5 in which m = 1, n = 1, p = 1, r = 3, s = 1, A- = CF3C00- and CL, R1 = 3-propylpyridinium, R2 = H, R3 = H, Compound 33 (obtained from Compound 30): Formula B5 in which m = 1, n = 1, p = 1, r = 3, s = 1, A- = CF3C00- and CL, R 1 = 3-propylpyridinium, R 2 = H, R 3 = H, R 4 = sec-butyl; Compound 34 (obtained from Compound 31): Formula B5 in which m = 1, n = 1, p = 1, r = 3, s = 1, A- = CF3C00- and CL, R1 = 3-propylpyridinium, R2 = H, R3 = H, C22H3202N3 + (Compound 33) [Ci] 25D -11.0 (c 0.02, MeOH). HRMS: C22H3202N3 + at 370.2489 (A = 0.08 ppm). C26H38N3O4S + (Compound 34) [α] D -0.4 (c 0.02, MeOH). 11H NMR (200MHz, CD30D) δ 8.99 (se, 1H, H14 '), 8.82 (m, 1H, H2'), 8.44 (m, 1H, H13 '), 8.00 (m. 1H, H6 '), 7.90-7.27 (m, 8H, H12', H11 ', H5', H4 '), 4.74 (t, J = 6.2, 2H, H7'), 4.23 (m, 1H, Hb), 3.55 (m, 2H, H1), 3.02 (m, 4H, H9, H3), 2.85 (m, 4H, Hg, Hc), 2 , (S, 3H, Hh), 2.00 (m, 4H, H8 ', H2,). 13C NMR (50 MHz, CD30D)? 173.1 (Ca), 148.5 (C2 '), 148.3 (C14'), 147.2 (C6 '), 143.9 (C13'), 139, 6 (C10 '), 137.9 (C3'), 125.0-129.8 (C12 ', C11', C5 ', C4'), 70.5 (Cb), 60.6 (C7 '), 43.1 (Cl '), 35.6 (C3), 31.9 (C9'), 28.6-31.5 (C8 ', C2', C8, Cc), 15.6 (Ch). HRMS: C211-13002N3S + at 388.2053 (A = -1.50 ppm). EXAMPLE 2 Evaluation of the Biocidal Properties of Different Synthesized Compounds The biocidal properties of the compounds synthesized previously were evaluated on 14 bacterial strains, 9 marine bacteria (Vibrio harveyi, Vibrio proteolyticus, Vibrio natriegens, Vibrio aestuarianus, Vibrio carchariae, Halomonas aquamarina, Polaribacter irgensii, Roseobacter litoralis, Shewanella putreficiens,), 3 terrestrial bacteria (Escherichia neck, Staphylococcus aureus, Pseudomonas aeruginosa) and 2 microalgae (Cylindrothecca closterium, Halamphora coffeaeformis). The biocidal properties of the synthesized compounds are also compared to a 4,5-dichloro-2-n-octyl-4-isothiazolin-3-one (DCOIT) reference substance, a biocidal compound of the product SeaNine ™ 211N, a marine antifoulant product. Rohm and Hass. Procedure Preparation of the solutions For each compound, a stock solution at 1 mg / ml in methanol is prepared. Different daughter solutions are prepared by cascade dilution of the stock solutions (0.01 lag / mL, 0.1 lag / mL, 1 μg / mL and 10 μg / mL). 100 μl of each solution are placed in the wells of a 96-well plate. The solvent is evaporated at ambient temperature and the plate is sterilized under UV irradiation.

Strains 9 strains of marine bacteria [Halomonas aquamarina (ATCC 14400), Polaribacter irgensii (ATCC 700398), Shewanella putrefaciens (ATCC 8071), Roseobacter litoralis (ATCC 49566), Vibrio aestuarianus (ATCC 35048), Vibrio harveyi (ATCC 700106), Vibrio natriegens (ATCC 14058), Vibrio proteolyticus (ATCC 53559) and Vibrio carchariae (ATCC 35084)] and 3 strains terrestrial bacteria [Escherichia neck (ATCC 11775), Staphylococcus aureus (ATCC 12600) and Pseudomonas aeruginosa (ATCC 10145)] were used. for the evaluation of the biocidal properties of the synthesized compounds (inhibition of growth and bacterial adhesion). Strains of marine bacteria were maintained in solid medium (autoclaved seawater, 0.5% peptone (oxoid) and 1% agar). Before the evaluation of the biocidal properties, the bacterial strains were cultivated in liquid medium (autoclaved seawater, 0.5% peptone (oxoid)). The terrestrial strains were maintained in a solid medium (2.5% nutrient medium (oxoid) and 1% agar). Before the evaluation of the antifouling properties, the bacterial strains were cultured in a liquid medium (purified water and 2.5% of nutrient medium (oxoid)).

Inhibition of the bacterial growth 100 μl of a bacterial suspension (2 × 10 8 cells / ml) are incubated with the test compounds for 48 h at 25 ° C. for the marine strains and at 37 ° C. for the terrestrial strains. In order to avoid cross-contamination a single strain is used per 96-well plate. The culture medium is used to perform a control experiment. Each experiment is repeated 6 times. The minimum inhibitory concentrations (MIC) are obtained by measuring the optical density at 620 nm using a spectrophotometer (Apollo LB912, Berthold Technologies). Inhibition of bacterial adhesion The 96-well plate used to evaluate the inhibition of bacterial growth is emptied. 100 μl of sterile seawater are used to rinse each well and then dried with room temperature air. Each well is labeled with 1041 of a 0.3% aqueous violet crystal solution. The plates are then washed three times with sterile deionized water, dried with filter paper and then with air at room temperature. The crystal violet is then solubilized by the addition of 100 μl of 95% ethanol in each well. The minimum inhibitory concentrations (MIC) are obtained by measuring the optical density at 595 nm using a plate reader (PolarSTAR Optima, BMG Labtech). Inhibition of microalgae growth and adhesion Two microphytobiral strains obtained from Algobank-Caen were studied: Cylindrotheca closterium AC170 (Ehrenberg) Reimann & Lewin (Bacillariophyta, Bacillariophyceae, Bacillariales, Bacillariaceae) and Halamphora coffeaeformis AC713 (Agardh) Levkov (Bacillariophyta, Bacillariophyceae, Naviculales, Amphipleuraceae). The microalgae are maintained in a F / 2 liquid medium under a constant light flux (140 i.tmol.m-1.s-2) at a temperature of 20 ° C. The amount of chlorophyll a microalgal suspension is determined. 5 mL of the suspension is collected using a GF / F filter (Whatman) which are immediately transferred to a vial containing 5 mL of analytical grade methanol. The vial is placed at a temperature of 4 ° C. for 30 minutes then the excitation at 485 nm and the emission at 645 nm are measured by means of a fluorimeter (PolarSTAR Optima BMG Labtech). A suspension of 0.1 mg of chlorophyll per ml is then prepared. 100 μl of this latter solution are placed in each well of the 96-well plate for 96h at a temperature of 20 ° C under a constant flow of light (140 μmol.m-1.s-2). The culture medium is used as a control. Each experiment is performed 6 times. The minimum inhibitory concentrations (MICs) are obtained by measuring the fluorescence (excitation at 485 nm and emission at 645 nm) using a fluorimeter (PolarSTAR Optima BMG Labtech). Results The results are shown in Table 3. These results highlight the biocidal properties of the synthesized compounds, in particular their property of growth inhibition, or adhesion, or both at the same time.

Indeed, depending on the strain, some compounds have Minimal Inhibition Concentrations (MICs) of growth, or adhesion, or both, ranging from 0.001 to 1 ppm. For some compounds these results are even better than those of the active substance 4,5-dichloro-2-n-octyl-4-isothiazolin-3-one (DCOIT), biocidal compound of the product Sea-NineTM 211N especially for the inhibition of adhesion.

By mixing the tested compounds, it is possible to obtain a product that is effective against a wide range of bacterial strains. Spectrum of activity of the synthesized compounds 14, 15, 17, 19, 20, 21, 22, 23, 24, 25, 29, 30, 31, 33 and 34: The synthesized compounds are particularly effective for inhibiting the growth of microorganisms. Algae Cylindrotheca closterium and Halamphora coffeaeformis, to inhibit the adhesion of marine bacteria Polaribacter irgensii (Gram -) and Shewanella putrefaciens (Gram -), and to inhibit the adhesion of terrestrial bacteria Staphylococcus aureus (Gram +) and Pseudomonas aeruginosa (Gram - ). These living organisms are specific to the phenomenon of soiling.

In particular, compound 15 is particularly effective in inhibiting growth of Cyhndrotheca closterium. Compound 17 is, in turn, particularly effective in inhibiting the growth of Cylindrotheca closterium and Halamphora coffeaeformis.

Table 3: Biocidal Properties of Synthesized Compounds and the biocidal compound of the Sea-Nine ™ 211N product (denoted Seanine). Strain Z, - 2, -, ..,...: Z-Marine 9 -0 4 ', 4. c. Terrestri al .. Z., -, c ,,, -._ ...> 9 9 9 "- ....:., 9-. - 1e, -c. -> -0 s micro-alga Q., c. i: - 9. c 9e, s? ..-- 9 a c c. -> 9 9, 4. ' c. C. 5. s 4.- C'er. - .V.: --- - '' ,,, Q, s `Z -...:>. cs Inhibition IC IA IC IC IC IC IC IC IC IC IC IC IC IC IC IC IC IC IC IC IC IC IC IC ID IC Molecule Compound 14 10 * * 0.01 * * * 10 0.1 0, 01 * * * * 0.01 10 0.01 0.1 1 1 Compound 15 * * * * * * * * * 10 0.1 * * 0.1 10 10 * 0.01 0.1 1 Compound 17 * * 0.01 * * * * * '0.1 0.01 * 0.1 0.01 0.1 * 0.01 * 0.01 0.1 0.01 Compound 19 * * * * * * 1 * * * * 10 0.01 10 '0.01 0.1 10. Compound 20 0.01 * * * * * * * * * 10 0.1 0.01 * 0.01 1 0.01 0.1 0.01 0.1 0.01 0.1 Compound 21 * * * * * * * * * * * 10 * * 10 10 * Compound 22 * 10 * * * * * * * * 0.1 10 f * '0.1' 0.1 1 10 0.1 0.1 10 Compound 23 * * 0.01 * * * * * '0.01 0.01 0.1 0.01 0.1 * 0.01 0.01 1 10 0.1 1 Compound 24 0.1 * * * * * * * * * 0.1 0.01 * * 0.01 * '0.1 * * * * Compound 25 * * * * * 10 0.1 * * 0.1 0.01 * * * Compound 29 * 1 0 , 1 * 0.01 0.01 * * * 1 0.01 0.01 0.01 0.1 * * Compound 30 * * 0.01 0.1 * * 10 0.01 0.01 0.01 * * * * * Compound 31 * 10 1 0.01 * * 10 0.1 0.01 0.01 0.01 * * * * Compound 33 10 10 * * '10 10 0.01 10 10 * * * * ff * * * * 0.01 0.1 0.1 10 Compound 34 * * * * f * 10 * * * 10 * * * * * * Seanine 1 1 0.1 0.1 * na. n / A. n / A. n / A. Legend: IC = Inhibition of Growth, IA = Inhibition of Adhesion 0.001; 0.01; 0.1; 1; 10: value of the Minimum Inhibition Concentration in ppm (MIC) * = inhibition greater than 10 ppm

Claims (13)

REVENDICATIONS1. Use of a compound represented by the following Formula I: ## STR5 ## wherein R 1 is R 1 (R 1) n an oxygen, a hydrogen, an optionally substituted alkyl group, an optionally substituted alkenyl group, an aryl group, a heterocycloalkyl group, a heteroaryl group, a heterocycloalkylium group or a heteroarylium group, R2 is a hydrogen, an alkoxycarbonyl group or an alkyl group; R 3 is hydrogen, alkoxycarbonyl, alkyl, R 4 is methyl, iso-propyl, sec-butyl, iso-butyl, a group represented by the following formulas: ## STR2 ## -% / * / * JUV,, VVVVY. -O4O H2No o H2N NOV NOVVV, W.VVVVV, JVVVV- VVVVV- 7 7 7 7 7 0 OHH2NNH 44 H where the wavy line indicates the binding site, m, n, and p are integers equal to 0 or 1; r is an integer of 1 to 12, preferably selected from 3, 4, 5, 6 and 7, and more preferably also still 3, s is an integer selected from 1, 2, 3, 4 and 5, preferably 1 or 2; A- is an anion selected from the group consisting of ci-, cficoo-, CF3SO3, r, Br-, C104- and mixtures thereof as a biocidal agent. 2. Use according to claim 1 for inhibiting the proliferation of a living organism, preferably a living organism selected from the group consisting of a marine bacterium, a terrestrial bacterium, an algae, and a micro-alga, in particular a marine bacterium , a terrestrial bacterium and a micro-algae. 3. Use according to claim 1 or 2 as a biocidal agent in a varnish, in anti-fouling paint, as a preservative in a cosmetic product, as a disinfectant of equipment, preferably medical equipment or in detergent. 4. Use according to any one of claims 1 to 3 as an antibacterial agent. 5. Use according to any one of claims 1 to 4, characterized in that the compound of formula 1 is selected from the compounds of formula 1 with the proviso that if: 1) m-0, n-0, pO, r -3, s-2 then R2 is not hydrogen, and 2) m-0, n-0, p0, r-2, s-2 then R2 is not hydrogen. 6. Compound represented by the following Formula 1: (R4) ## STR2 ## (n + m) A-Formula 1 wherein R1 is oxygen, hydrogen; an optionally substituted alkyl group; an optionally substituted alkenyl group; an aryl group; a heterocycloalkyl group; a heteroaryl group; a heterocycloalkylium group or a heteroarylium group; R2 is hydrogen; an alkoxycarbonyl group; an alkyl group; R3 is hydrogen; an alkoxycarbonyl group; an alkyl group; R4 is methyl; iso-propyl; sec-butyl; iso-butyl; a group represented by the following formulas: ## STR2 ## where the wavy line indicates the binding site, m, n, and p are whole numbers. equal to 0 or 1; r is an integer from 1 to 12, preferably selected from 3, 4, 5, 6 and 7, and more preferably still equal to 3; s is an integer selected from 1, 2, 3, 4 and 5, preferably 1 or 2; A- is an anion selected from the group consisting of ci-, cficoo-, CF3SO3, r, Br-, c104- and mixtures thereof; with the proviso that if: 1) m - 0, n - 0, p - 0, r - 3, s - 2 then R2 is not hydrogen and 2) m - 0, n - 0, p - 0, r - 2, s - 2 then R2 is not hydrogen. 7. Compound according to claim 6 characterized in that R1 is an oxygen, a hydrogen; an alkyl group substituted with a heteroaryl group or a heteroarylium group, preferably a hydrogen; 3-propylpyridine or 3-propylpyridinium, R2 is hydrogen; an alkoxycarbonyl group, preferably a hydrogen or tert-butyloxycarbonyl, R3 is hydrogen; an alkoxycarbonyl group, preferably a hydrogen, and R4 is sec-butyl; a group represented by the following formulas: 8. A compound according to claim 6 or 7 selected from the compounds of the following Table 1: Table 1 Compound No. Formula Compound No. Formula 14 Boc Boc NN HO NN HO 0 17 0. 19 0 5. HO) BOC Boc 20 CF3C00-N 21 cF3c00-I F12 + I O 112 + NI-1 * HO NH + N CF3C00- 01 CF3C00-Ho22 0 I2 + n 23 o). FN NH HO). ## STR5 ## ## STR5 ## ## STR2 ## ## STR2 ## ## STR2 ## ## STR1 ## wherein CF3C00-CF3C00-Boc 0 H2 + N + 10 -N a N HO + HO / (CF3C00-S / N) CF3C00- 0 H2 + NO N \ N + CI- SI NH + CF3C00- in which Boc is the tert-butoxycarbonyl group. 9. Process for obtaining a compound as defined in any one of claims 6 to 8, comprising the following step: ## STR2 ## in which X is a halogen, for example bromine, chlorine, fluorine, iodine, preferably chlorine. A composition comprising at least one compound of Formula I as defined in claim 1 or at least one compound as defined in any one of claims 6 to 8 or obtained by the process of claim 9 and an excipient and / or a solvent. 11. Composition according to claim 10, characterized in that it is an anti-fouling paint. A compound of Formula 1 as defined in claim 1 or a compound as defined in any one of claims 6 to 8 or obtained by the process of claim 9 for use as a medicament. 13. A compound according to claim 12 for use as an antibiotic.