WO2014191789A1 - Nouveaux acides aminés cationiques, compositions pharmaceutiques les contenant et leur utilisation pour le traitement d'infections bactériennes - Google Patents

Nouveaux acides aminés cationiques, compositions pharmaceutiques les contenant et leur utilisation pour le traitement d'infections bactériennes Download PDF

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WO2014191789A1
WO2014191789A1 PCT/IB2013/001772 IB2013001772W WO2014191789A1 WO 2014191789 A1 WO2014191789 A1 WO 2014191789A1 IB 2013001772 W IB2013001772 W IB 2013001772W WO 2014191789 A1 WO2014191789 A1 WO 2014191789A1
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compound
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treatment
drug
formula
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PCT/IB2013/001772
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Universite Pierre Et Marie Curie (Paris 6)
Centre National De La Recherche Scientifique
KAROYAN, Philippe
MOUMNE, Roba
BOULLET, Héloise
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Priority to PCT/IB2013/001772 priority Critical patent/WO2014191789A1/fr
Priority to PCT/EP2014/060917 priority patent/WO2014191392A1/fr
Publication of WO2014191789A1 publication Critical patent/WO2014191789A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
    • A61K31/404—Indoles, e.g. pindolol
    • A61K31/4045—Indole-alkylamines; Amides thereof, e.g. serotonin, melatonin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/06—Tripeptides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/02—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link
    • C07K5/0202—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link containing the structure -NH-X-X-C(=0)-, X being an optionally substituted carbon atom or a heteroatom, e.g. beta-amino acids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/06—Dipeptides
    • C07K5/06139—Dipeptides with the first amino acid being heterocyclic
    • C07K5/06156—Dipeptides with the first amino acid being heterocyclic and Trp-amino acid; Derivatives thereof
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/08—Tripeptides
    • C07K5/0815—Tripeptides with the first amino acid being basic
    • C07K5/0817—Tripeptides with the first amino acid being basic the first amino acid being Arg
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Definitions

  • the present invention relates to new cationic amino acids pharmaceutical compositions containing the same and their use for the treatment of bacterial infections.
  • CAPs have been identified in all the animal kingdom and 1200 are listed in the databases of peptides (Morris, M.; Vidal, P.; Chaloin, L.; Heitz, F.; Divita, G. Nucl. Acids Res. 1997, 25, 2730- 2736 ; Morris, M. C; Depollier, J.; Mery, J.; Heitz, F.; Divita, G. Nat Biotech 2001, 19, 1173- 1176). These are generally amphiphilic peptides of 20-50 residues.
  • the micro-organisms living in an aqueous medium can be observed in two forms: planktonic (suspended in their natural surroundings) or in a biofilm.
  • Biofilm is the result of adhesion, development and cooperation within a community of micro-organisms.
  • a biofilm is composed of nutrients, living or dead microorganisms and extracellular matrix. Through the flow channels in its matrix, the biofilm can carry oxygen and nutrients to the upper layers of micro-organisms, to remove the waste towards the outside and to protect the microorganisms from external attacks.
  • the extracellular matrix is composed of water (95%) and extracellular polymeric substances (EPS) comprising polysaccharides (40-95%), proteins (1-60%), nucleic acids (1 to 10%>) and lipids (1-40%).
  • EPS extracellular polymeric substances
  • the biofilm is often a point of attachment for macroscopic organisms such as algae, shellfish and some invertebrates.
  • the biofilm is formed in several steps: formation of a primary film, adhesion of microorganisms, growth and secretion of EPSs, and finally the formation of biofilm.
  • the formation of said primary film starts from the introduction of a surface in the marine environment. It modifies the physicochemical properties of said surface and facilitates the future adhesion of microorganisms. Simultaneously with the formation of this film, there is a transport of microorganisms to the surface either passively (current or diffusion) or in an active way, thanks to the presence of flagella or pili on some strains of bacteria.
  • the grip of microorganisms on the surface is in two stages: the reversible adsorption involving weak interactions (hydrogen bonds, Van der Waals force). Then, the so-called irreversible adhesion stage involving biological phenomena, such as the expression of genes involved in adhesion, production of biopolymers or communication between cells.
  • Biofilm begins to structure in the shape of columns or fungi comprising microorganisms within the extracellular matrix, said matrix comprising circulation channels.
  • Biofilms on the surface of medical devices carry the bacteria that cause hospital-acquired infections and serve as a reservoir for plasmids tha carry genes of antibiotic resistance. It is possible to limit the development of biofilms by grafting for example antibiotics on medical equipment, but this approach does not avoid the emergence of resistant strains.
  • endocytosis This process allows the cell to import the hydrophilic compounds it needs to operate.
  • a receptor eg transferrin
  • bioactive compounds such as oligonucleotides.
  • Liposomes have also been proposed for the intracellular delivery of bioactive compounds, but their induced cytotoxicity and the fact that they are internalized by endocytosis limit their scope.
  • One of the aims of the invention is to provide synthetic compounds bearing beta- amino acids presenting an improved stability toward plasma degradation for the treatment of bacterial infections.
  • Another aim of the invention is to provide new synthetic compounds bearing beta- amino acids.
  • Still another aim of the invention is to provide pharmaceutical compositions comprising new synthetic compounds bearing beta-amino acids.
  • Still another aim of the invention is to provide cosmetic compositions comprising new synthetic compounds bearing beta-amino acids.
  • Still another aim of the invention is to provide new synthetic compounds bearing beta- amino acids for their use in anti-bio film surface treatment.
  • Still another aim of the invention is to provide new synthetic compounds bearing beta- amino acids for their use in the preparation of vector peptides.
  • the present invention relates to a compound having the following formula (I):
  • Ri represents the lateral chain of ornithine or arginine
  • R 2 represents H, a protecting group of the amino function, or an amino acid selected from the group consisting of:
  • R4 is as defined above and F, G, H, I and J represent independently from each other: H, an alkyl group, an aryl group or CF 3 .
  • R 3 represents H, an alkyl, an alkylaryl group such as a substituted benzyl group with A, B, C, D and E defined above or a substituted ethylbenzene group with A, B, C, D and E defined above;
  • R 3 represent together an amino acid selected from the group consisting of:
  • Y represents O or NH
  • R 6 represents H or an alkyl, an alkylaryl group such as a substituted benzyl group with A, B, C, D and E defined above or a substituted ethylbenzene group with A, B, C, D and E defined above; or
  • Y represents O or NH
  • 3 ⁇ 4 represents a H, an alk l group, a substituted benzyl group with A, B, C, D and E defined above; or
  • F, G, H, I and J represent independently from each other: H, an alkyl group, an aryl group or CF 3 , Y represents O or NH, and Re represents a H, or an alkyl, an alkylaryl group such as a substituted benzyl group with A, B, C, D and E defined above or a substituted ethylbenzene group with A, B, C, D and E defined above; provided that:
  • R 2 represents an amino acid selected from the group as defined above, then X represents O or NH, and R 3 represents an alkyl or a substituted benzyl group with F, G, H, I and J defined above; and
  • R 2 represents H, Fmoc, then X and R 3 represent together an amino acid selected from the group defined above;
  • the peptides of the invention have antimicrobial activity and are defined as antimicrobial peptides.
  • antimicrobial peptides refers to an agent that kills microorganisms or inhibits their growth.
  • Said microorganisms can be bacteria, fungi, viruses or yeast.
  • said antimicrobial peptides are antibacterial peptides.
  • the Inventors have unexpectedly found that the simultaneous introduction of two lateral chains of ornithine or arginine giving thus two positive charges instead of one, allows to reduce the number of residues that must be present in the molecule and thus the size of the peptides to synthesize, while keeping the antibiotic activity and at the same time increasing the stability toward proteolytic degradation of said peptides given thus peptides, liable to be active.
  • the reduction of the size of the peptides also provides compounds liable to escape from the immune system and thus to prevent immune reactions.
  • a further advantage of the invention is the use of beta amino acid instead of alpha amino acid allowing to incorporate directly said beta amino acid into peptides without encountering the problems due to the steric hindrance of the quaternary centre bearing both Ri .
  • Ri represents the lateral chain of ornithine and arginine
  • Ri represents the lateral chain of ornithine or both Ri represent the lateral chain of arginine, or one Ri represents the lateral chain of ornithine and the other one represents the lateral chain of arginine.
  • a basic group such as the nitrogen of the ornithine or arginine moiety or an amino group present on the molecule can be under a salt form, the salt being any pharmaceutically acceptable salt obtained by reaction of an inorganic acid, an organic acid or a halogenoalkyl on an amino group to give a quaternary ammonium.
  • inorganic acids allowing to obtain pharmaceutically acceptable salts include, without being limited to them: hydrochloric acid, hydrobromic acid, hydroiodic acid, nitric acid, carbonic acid, formic acid, monohydrogenocarbonic acid, phosphoric acid, monohydrogenophosphoric acid, dihydrogenophosphoric acid, perchloric acid, sulfuric acid, monohydrogenosulfuric acid.
  • organic acid allowing to obtain pharmaceutically acceptable salts include, without being limited to them, acetic acid, lactic acid, propionic acid, butyric acid, isobutyric acid, palmitic acid, malic acid, glutamic acid, hydroxymalic acid, malonic acid, benzoic acid, succinic acid, glycolic acid, suberic acid, fumaric acid, mandelic acid, phthalic acid, salicylic acid, benzenesulfonic acid, /?-tolylsulfonic acid, citric acid, tartaric acid, methanesulfonic acid, hydroxynaphthoic acid, trifluoroacetic acid.
  • compounds of the invention are under the form of trifluoroacteic salts.
  • protecting group of the amino function refers for example, but without being limited to them, to Fmoc, Z and Boc groups.
  • alkyl group refers to a linear alkyl group or a branched alkyl group or a cycloalkyl group.
  • Said alkyl group can be from Ci to C 15 , advantageously from Ci to C 7 .
  • linear alkyl group from Ci to C 7 is meant a group such as methyl, ethyl, propyl, butyl, pentyl, hexyl or heptyl.
  • branched alkyl group is meant an alkyl group as defined above bearing substituents selected from the list of linear alkyl groups defined above, said linear alkyl group being also liable to be branched.
  • alkyl group and of linear and branched alkyl applies to the entire specification.
  • cycloalkyl group from C 3 to C 7 is meant a group such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or cycloheptyl. Such groups can also be substituted by a linear or branched alkyl group as defined above.
  • cycloalkyl group applies also to the entire specification.
  • aryl group refers to any functional group or substituent derived from a simple aromatic ring or heteroaromatic group.
  • the "aryl group” can be substituted by one or more groups chosen independently among an halogen, a linear or branched (Ci-C 7 )-alkyl, a (C 3 -C 7 )-cycloalkyl, CN, CF 3 , OH, OR x , NH 2 , NHPv x , NPv x R y , R x and R y being a linear or branched (Ci-C 7 )-alkyl, a (C 3 -C 7 )- cycloalkyl, an aryl substituted or not, CH 2 -aryl, CO-(Ci-C 7 )-alkyl or cycloalkyl, CO-aryl, C0 2 H, C0 2 -(Ci-C 7 )-alkyl or cycloalkyl.
  • the term "heteroaromatic” refers to a compound having the characteristics of an aromatic compound whilst having at least one non-carbon
  • the heteroaromatic can be substituted by one or more groups chosen independently among those defined for aryl.
  • alkylarylgroup refers to a group constituted of an alkyl such as defined above linked to an aryl group such as defined above.
  • R 3 or 5 represents an alkyl
  • said alkyl is a C 1 -C 7 alkyl, more advantageously a methyl group.
  • bacteria infections refers to any infection caused by bacteria, in particular a pathogenic bacteria.
  • the amino-acid defined in R 2 and X-R 3 or the beta-amino-acid can be independently from each other R or S.
  • the amino-acid is S defined in R 2 and X-R 3 .
  • the present invention relates to a compound having the following formula (I):
  • Ri represents the lateral chain of ornithine or arginine
  • R 2 represents H, a protecting group of the amino function, or an amino acid selected from the group consisting of: ⁇
  • R4 is as defined above and F, G, H, I and J represent independently from each other: H, an alkyl group, an aryl group or CF 3 .
  • R 3 represents H or an alkyl, an alkylaryl group such as a substituted benzyl group with A, B, C, D and E defined above or a substituted ethylbenzene group with A, B, C, D and E defined above; or
  • R 3 represent together an amino acid selected from the group consisting of:
  • Y represents O or NH
  • R 6 represents H or an alkyl, an alkylaryl group such as a substituted benzyl group with A, B, C, D and E defined above, or a substituted ethylbenzene group with A, B, C, D and E defined above; or
  • Y represents O or NH
  • R6 represents a H, C1-C15 alkyl or a substituted benzyl group with A, B, C, D and E defined above; or
  • F, G, H, I and J represent independently from each other: H, an alkyl group, an aryl group or CF 3 , Y represents O or NH, and Re represents a H, or an alkyl or a substituted benzyl group with A, B, C, D and E defined above;
  • R 2 represents an amino acid selected from the group as defined above, then X represents O or NH, and R 3 represents an alkyl or a substituted benzyl group with F, G, H, I and J defined above and provided that the following compounds are excluded:
  • X and R 3 represent together an amino acid selected from the group defined above;
  • the present invention relates to a compound for its use as a drug for the treatment of microbial infections, as defined above, wherein said antimicrobial peptide has an activity directed against Gram-positive and Gram-negative bacteria.
  • Gram-positive bacteria refers to the two bacterial phyla defined in the Bergey's manual of systematic bacteriology (2 nd edition, G. M. Garrity (ed.), Springer, 2005), Actinobacteria, and Firmicutes, and include the well known genera Staphylococcus, Streptococcus; Enterococcus, Listeria and Bacillus,
  • Gram-negative bacteria refers to 22 bacterial phyla defined in the Bergey's manual of systematic bacteriology (2 nd edition, G. M. Garrity, Springer, 2005), Aquificae, Thermotogae, Thermodesulfobacteria, Deinococcus-Thermus, Chrysiogenetes, Chloroflexi, Thermomicrobia, Nitrospira, Deferribacteres, Cyanobacteria, Chlorobia, Proteobacteria, Planctomycetes, Chlamydiae, Spirochaetes, Fibrobacteres, Acidobacteres, Bacteroidetes, Fusobacteria, Verrucomicrobia, Dictyoglomi, and Gemmatimonadetes.
  • Proteobacteria include a large number of human pathogens such as the Enterobacteriaceae, Pseudomonadaceae, Vibrionaceae, Moraxellaceae, Neisseriaceae and Pasteur ellaceae families.
  • the present invention relates to a compound for its use as a drug for the treatment of microbial infections, as defined above, wherein said Gram- positive bacteria are selected from the group consisting of: Staphylococcus aureus, in particular S. aureus ATCC25923 or S. aureus 1199B, or Enterococcus faecalis, in particular ATCC29212.
  • Staphylococcus aureus refers to a pathogen responsible of numerous infections such as furuncles and carbuncles (a collection of furuncles), staphylococcal scalded skin syndrome (SSSS), septic arthritis, staphylococcal endocarditis (infection of the heart valves) and pneumonia.
  • Enterococcus faecalis refers to a pathogen responsible of endocarditis and bacteremia, urinary tract infections (UTI), meningitis, and other infections in humans.
  • the present invention relates to a compound for its use as a drug for the treatment of microbial infections as defined above, wherein said Gram- negative bacteria are selected from the group consisting of: Escherichia coli, in particular ATCC25922, Pseudomonas aeruginosa, in particular ATCC27853 or Acinetobacter baumannii, in particular ATCC 19606.
  • Escherichia coli refers to Enterotoxigenic E. coli (ETEC), Enteropathogenic E. coli (EPEC), Enteroinvasiveji. coli (EIEC), Enterohemorrhagic _E. coli (EHEC), Enteroaggregative__E. coli (EAEC), Uropathogenic E. coli (UPEC), or E. coli responsive of Neonatal meningitis.
  • ETEC Enterotoxigenic E. coli
  • EPEC Enteropathogenic E. coli
  • EIEC Enteroinvasiveji. coli
  • EHEC Enterohemorrhagic _E. coli
  • EAEC Enteroaggregative__E. coli
  • UPEC Uropathogenic E. coli
  • Pseudomonas aeruginosa refers to a pathogen responsible of pneumonia, Septic shock, urinary tract infection, gastrointestinal infection and skin and soft tissue infections.
  • Acinetobacter baumannii refers to a pathogen responsible of pulmonary infections, septicaemia, and burn and wound infections.
  • the present invention relates to a compound for its use as a drug for the treatment of microbial infections as defined above, having the following general formula (II):
  • R l s R 2 , R 3 and X are as defined above.
  • the present invention relates to a compound of formula (II) for its use as a drug for the treatment of microbial infections, as defined above, having the following general formula (Ha):
  • R l s R 3 , R4 and X are as defined above.
  • the present invention relates to a compound of formula (Ila) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents H, C 10 H 7 CO, C 22 H 25 CO, or Fmoc, X represents O or NH and R 3 represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (Ila) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents H, X represents O and R 3 represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (Ila) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents H, X represents O and R 3 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (Ila) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents H, X represents NH and R 3 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (Ila) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents Fmoc, X represents O and R 3 represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (Ila) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents C 10 H 7 CO, X represents O and R 3 represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (Ila) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents C 22 H 25 CO, X represents O and R 3 represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (Ila) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents Fmoc, X represents O and R 3 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (Ila) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents C 10 H 7 CO, X represents O and R 3 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (Ila) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents C 22 H 25 CO, X represents O and R 3 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (Ila) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents Fmoc, X represents NH and R 3 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (Ila) for its use as a drug as a drug for the treatment of microbial infections, as defined above, having the following general formula (II-a-1):
  • R 3 , R 4 and X are as defined above.
  • the present invention relates to a compound of formula (IIa-1) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents H, C 10 H 7 CO, C 22 H 25 CO, or Fmoc, X represents O or NH and R 3 represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (IIa-1) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents H, X represents O and R 3 represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (IIa-1) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents C 10 H 7 CO, X represents O and R 3 represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (IIa-1) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents C 22 H 25 CO, X represents O and R 3 represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (IIa-1) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents H, X represents O and R 3 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (IIa-1) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents H, X represents NH and R 3 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (IIa-1) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents Fmoc, X represents O and R 3 represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (IIa-1) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents C 10 H 7 CO, X represents O and R 3 represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (IIa-1) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents C 22 H 25 CO, X represents O and R 3 represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (IIa-1) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents Fmoc, X represents O and R 3 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (IIa-1) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents C 10 H 7 CO, X represents O and R 3 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (IIa-1) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents C 22 H 25 CO, X represents O and R 3 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (IIa-1) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents Fmoc, X represents NH and R 3 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (IIa-1) for its use as a drug for the treatment of microbial infections, as defined above, having one of the following formulae:
  • the present invention relates to a compound of formula (IIa-1) for its use as a drug for the treatment of microbial infections, as defined above, having one of the following formulae:
  • the present invention relates to a compound of formula (Ila) for its use as a drug for the treatment of microbial infections, as defined above, having the following general formula (IIa-2):
  • R 3 , R4 and X are as defined above.
  • the present invention relates to a compound of formula (IIa-2) for its use as a drug for the treatment of microbial infections, as defined above, wherein R4 represents H or Fmoc, X represents O or NH and R 3 represents H, C1-C7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (IIa-2) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents H, X represents O and R 3 represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (IIa-2) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents H, X represents O and R 3 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (IIa-2) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents H, X represents NH and R 3 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (IIa-2) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents Fmoc, X represents O and R 3 represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (IIa-2) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents Fmoc, X represents O and R 3 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (IIa-2) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents Fmoc, X represents NH and R 3 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (IIa-2) for its use as a drug for the treatment of microbial infections, as defined above, having one of the following formulae:
  • the present invention relates to a compound of formula (IIa-2) for its use as a drug for the treatment of microbial infections, as defined above, having one of the following formulae:
  • the present invention relates to a compound of formula (I) for its use as a drug for the treatment of microbial infections, as defined above, having the following general formula II- 1):
  • R l s R 2 , R 3 and X are as defined above.
  • the present invention relates to a compound of formula (I) for its use as a drug for the treatment of microbial infections, as defined above, having the following general formula ( ⁇ -2):
  • the present invention relates to a compound of formula (II) for its use as a drug for the treatment of microbial infections, as defined above, having the following general formula (III):
  • the present invention relates to a compound of formula (III) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents H or Fmoc, X represents O or NH and R 3 represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (III) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents H, X represents O and R 3 represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (III) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents H, X represents O and R 3 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (III) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents H, X represents NH and R 3 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (III) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents Fmoc, X represents O and R 3 represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (III) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents Fmoc, X represents O and R 3 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (III) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents C 10 H 7 CO, X represents O and R 3 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (III) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents Fmoc, X represents NH and R 3 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (III) for its use as a drug for the treatment of microbial infections, as defined above, having the following general formula (Ilia): wherein R 3 , R 4 and X are as defined above.
  • the present invention relates to a compound of formula (Ilia) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents H, C 10 H 7 CO or Fmoc, X represents O or NH and R 3 represents H, Ci- C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (Ilia) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents H, X represents O and R 3 represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (Ilia) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents H, X represents O and R 3 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (Ilia) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents H, X represents NH and R 3 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (Ilia) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents Fmoc, X represents O and R 3 represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (Ilia) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents C 10 H 7 CO, X represents O and R 3 represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (Ilia) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents Fmoc, X represents O and R 3 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (Ilia) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents C 10 H 7 CO, X represents O and R 3 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (Ilia) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents Fmoc, X represents NH and R 3 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (III) for its use as a drug for the treatment of microbial infections, as defined above, having the following general formula (Illb):
  • R 3 , R 4 and X are as defined above.
  • the present invention relates to a compound of formula (Illb) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents H or Fmoc, X represents O or NH and R 3 represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (Illb) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents H, X represents O and R 3 represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (Illb) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents H, X represents O and R 3 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (Illb) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents H, X represents NH and R 3 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (Illb) for its use as a drug for the treatment of microbial infections, as defined above, wherein R4 represents Fmoc, X represents O and R 3 represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (Illb) for its use as a drug for the treatment of microbial infections, as defined above, wherein R4 represents Fmoc, X represents O and R 3 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (Illb) for its use as a drug for the treatment of microbial infections, as defined above, wherein R4 represents Fmoc, X represents NH and R 3 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (II) for its use as a drug for the treatment of microbial infections, as defined above, having the following general formula IV):
  • R l s R 3 R4, and X are as defined above.
  • the present invention relates to a compound of formula (IV) for its use as a drug for the treatment of microbial infections, as defined above, wherein R4 represents H or Fmoc, X represents O or NH and R 3 represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (IV) for its use as a drug for the treatment of microbial infections, as defined above, wherein R4 represents H, X represents O and R 3 represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (IV) for its use as a drug for the treatment of microbial infections, as defined above, wherein R4 represents H, X represents O and R 3 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (IV) for its use as a drug for the treatment of microbial infections, as defined above, wherein R4 represents H, X represents NH and R 3 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (IV) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents Fmoc, X represents O and R 3 represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (IV) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents Fmoc, X represents O and R 3 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (IV) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents Fmoc, X represents NH and R 3 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (IV) for its use as a drug for the treatment of microbial infections, as defined above, having the following general formula IVa):
  • R 3 , R 4 and X are as defined above.
  • the present invention relates to a compound of formula (IVa) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents H or Fmoc, X represents O or NH and R 3 represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (IVa) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents H, X represents O and R 3 represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (IVa) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents H, X represents O and R 3 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (IVa) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents H, X represents NH and R 3 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (IVa) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents Fmoc, X represents O and R 3 represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (IVa) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents Fmoc, X represents O and R 3 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (IVa) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents Fmoc, X represents NH and R 3 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (IV) for its use as a drug for the treatment of microbial infections, as defined above, having the following general formula IVb):
  • R 3 , R 4 and X are as defined above.
  • the present invention relates to a compound of formula (IVb) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents H or Fmoc, X represents O or NH and R 3 represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (IVb) for its use as a drug for the treatment of microbial infections, as defined above, wherein R4 represents H, X represents O and R 3 represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (IVb) for its use as a drug for the treatment of microbial infections, as defined above, wherein R4 represents H, X represents O and R 3 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (IVb) for its use as a drug for the treatment of microbial infections, as defined above, wherein R4 represents H, X represents NH and R 3 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (IVb) for its use as a drug for the treatment of microbial infections, as defined above, wherein R4 represents Fmoc, X represents O and R 3 represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (IVb) for its use as a drug for the treatment of microbial infections, as defined above, wherein R4 represents Fmoc, X represents O and R 3 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (IVb) for its use as a drug for the treatment of microbial infections, as defined above, wherein R4 represents Fmoc, X represents NH and R 3 represents CH 3 or a benzyl group, wherein R l s R 3 R4, and X are as defined above.
  • the present invention relates to a compound of formula (II) for its use as a drug for the treatment of microbial infections, as defined above, having the following gen ral formula (V):
  • the present invention relates to a compound of formula (V) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents H or Fmoc, X represents O or NH and R 3 represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (V) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents H, X represents O and R 3 represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (V) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents H, X represents O and R 3 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (V) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents H, X represents NH and R 3 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (V) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents Fmoc, X represents O and R 3 represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (V) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents Fmoc, X represents O and R 3 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (V) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents Fmoc, X represents NH and R 3 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (V) for its use as a drug for the treatment of microbial infections, as defined above, having the following general formula (V)
  • the present invention relates to a compound of formula (Va) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents H or Fmoc, X represents O or NH and R 3 represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (Va) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents H, X represents O and R 3 represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (Va) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents H, X represents O and R 3 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (Va) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents H, X represents NH and R 3 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (Va) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents Fmoc, X represents O and R 3 represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (Va) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents Fmoc, X represents O and R 3 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (Va) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents Fmoc, X represents NH and R 3 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (V) for its use as a drug for the treatment of microbial infections, as defined above, having the following general formula (Vb):
  • R 3 , R 4 and X are as defined above.
  • the present invention relates to a compound of formula (Vb) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents H or Fmoc, X represents O or NH and R 3 represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (Vb) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents H, X represents O and R 3 represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (Vb) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents H, X represents O and R 3 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (Vb) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents H, X represents NH and R 3 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (Vb) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents Fmoc, X represents O and R 3 represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (Vb) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents Fmoc, X represents O and R 3 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (Vb) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents Fmoc, X represents NH and R 3 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (II) for its use as a drug for the treatment of microbial infections, as defined above, having the following general formula VI):
  • R l s R 3 R 4 , and X are as defined above.
  • the present invention relates to a compound of formula (VI) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents H or Fmoc, X represents O or NH and R 3 represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (VI) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents H, X represents O and R 3 represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (VI) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents H, X represents O and R 3 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (VI) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents H, X represents NH and R 3 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (VI) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents Fmoc, X represents O and R 3 represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (VI) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents Fmoc, X represents O and R 3 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (VI) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents Fmoc, X represents NH and R 3 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (VI) for its use as a drug for the treatment of microbial infections, as defined above, having the following general formula Via):
  • R 3 , R 4 and X are as defined above.
  • the present invention relates to a compound of formula (Via) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents H or Fmoc, X represents O or NH and R 3 represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (Via) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents H, X represents O and R 3 represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (Via) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents H, X represents O and R 3 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (Via) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents H, X represents NH and R 3 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (Via) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents Fmoc, X represents O and R 3 represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (Via) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents Fmoc, X represents O and R 3 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (Via) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents Fmoc, X represents NH and R 3 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (VI) for its use as a drug for the treatment of microbial infections, as defined above, having the following general formula VIb):
  • R 3 , R 4 and X are as defined above.
  • the present invention relates to a compound of formula (VIb) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents H or Fmoc, X represents O or NH and R 3 represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (VIb) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents H, X represents O and R 3 represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (VIb) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents H, X represents O and R 3 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (VIb) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents H, X represents NH and R 3 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (VIb) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents Fmoc, X represents O and R 3 represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (VIb) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents Fmoc, X represents O and R 3 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (VIb) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents Fmoc, X represents NH and R 3 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (II) for its use as a drug for the treatment of microbial infections, as defined above, having the followin general formula (VII):
  • R l s R 3 R 4 , and X are as defined above.
  • the present invention relates to a compound of formula (VII) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents H or Fmoc, X represents O or NH and R 3 represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (VII) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents H, X represents O and R 3 represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (VII) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents H, X represents O and R 3 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (VII) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents H, X represents NH and R 3 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (VII) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents Fmoc, X represents O and R 3 represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (VII) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents Fmoc, X represents O and R 3 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (VII) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents Fmoc, X represents NH and R 3 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (VII) for its use as a drug for the treatment of microbial infections, as defined above, having the following general formula Vila):
  • R 3 , R 4 and X are as defined above.
  • the present invention relates to a compound of formula (Vila) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents H or Fmoc, X represents O or NH and R 3 represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (Vila) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents H, X represents O and R 3 represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (Vila) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents H, X represents O and R 3 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (Vila) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents H, X represents NH and R 3 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (Vila) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents Fmoc, X represents O and R 3 represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (Vila) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents Fmoc, X represents O and R 3 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (Vila) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents Fmoc, X represents NH and R 3 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (VII) for its use as a drug for the treatment of microbial infections, as defined above, having the followin general formula (Vllb):
  • R 3 , R 4 and X are as defined above.
  • the present invention relates to a compound of formula (Vllb) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents H or Fmoc, X represents O or NH and R 3 represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (Vllb) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents H, X represents O and R 3 represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (Vllb) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents H, X represents O and R 3 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (Vllb) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents H, X represents NH and R 3 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (Vllb) for its use as a drug for the treatment of microbial infections, as defined above, wherein R4 represents Fmoc, X represents O and R 3 represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (Vllb) for its use as a drug for the treatment of microbial infections, as defined above, wherein R4 represents Fmoc, X represents O and R 3 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (Vllb) for its use as a drug for the treatment of microbial infections, as defined above, wherein R4 represents Fmoc, X represents NH and R 3 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (II) for its use as a drug for the treatment of microbial infections, as defined above, having the followin general formula (VIII):
  • R l s R 3 R4, F to J and X are as defined above.
  • the present invention relates to a compound of formula (VIII) for its use as a drug for the treatment of microbial infections, as defined above, wherein R4 represents H or Fmoc, X represents O or NH and R 3 represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (VIII) for its use as a drug for the treatment of microbial infections, as defined above, wherein R4 represents H, X represents O and R 3 represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (VIII) for its use as a drug for the treatment of microbial infections, as defined above, wherein R4 represents H, X represents O and R 3 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (VIII) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents H, X represents NH and R 3 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (VIII) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents Fmoc, X represents O and R 3 represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (VIII) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents Fmoc, X represents O and R 3 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (VIII) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents Fmoc, X represents NH and R 3 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (VIII) for its use as a drug for the treatment of microbial infections, as defined above, having the following general formula (Villa):
  • R 3 , R 4 , F to J and X are as defined above.
  • the present invention relates to a compound of formula (Villa) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents H or Fmoc, X represents O or NH and R 3 represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (Villa) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents H, X represents O and R 3 represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (Villa) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents H, X represents O and R 3 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (Villa) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents H, X represents NH and R 3 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (Villa) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents Fmoc, X represents O and R 3 represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (Villa) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents Fmoc, X represents O and R 3 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (Villa) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents Fmoc, X represents NH and R 3 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (VIII) for its use as a drug for the treatment of microbial infections, as defined above, having the followin general formula (Vlllb):
  • R 3 , R 4 , F to J and X are as defined above.
  • the present invention relates to a compound of formula (Vlllb) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents H or Fmoc, X represents O or NH and R 3 represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (Vlllb) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents H, X represents O and R 3 represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (Vlllb) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents H, X represents O and R 3 represents CH 3 or a benzyl group, and in particular F, G, I, J represent a hydrogen atom and H represents tBu or CF 3 .
  • the present invention relates to a compound of formula (Vlllb) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents H, X represents NH and R 3 represents CH 3 or a benzyl group, and in particular F, G, I, J represent a hydrogen atom and H represents tBu or CF 3 .
  • the present invention relates to a compound of formula (Vlllb) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents Fmoc, X represents O and R 3 represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (Vlllb) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents Fmoc, X represents O and R 3 represents CH 3 or a benzyl group, and in particular F, G, I, J represent a hydrogen atom and H represents tBu or CF 3 .
  • the present invention relates to a compound of formula (Vlllb) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 4 represents Fmoc, X represents NH and R 3 represents CH 3 or a benzyl group, and in particular F, G, I, J represent a hydrogen atom and H represents tBu or CF 3 .
  • the present invention relates to a compound of formula (I) for its use as a drug for the treatment of microbial infections, as defined above, having the following general formula (IX):
  • R l s R 2 , Re and Y are as defined above.
  • the present invention relates to a compound of formula (IX) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents H or Fmoc, X represents O or NH and 3 ⁇ 4 represents H, C 1 -C7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (IX) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents H, X represents O and 5 represents H, C 1 -C7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (IX) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents H, X represents O and 5 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (IX) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents H, X represents NH and 5 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (IX) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents Fmoc, X represents O and 5 represents H, C 1 -C7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (IX) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents Fmoc, X represents O and 5 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (IX) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents Fmoc, X represents NH and 5 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (IX) for its use as a drug for the treatment of microbial infections, as defined above, having the following general formula IXa):
  • R 2 , Re and Y are as defined above.
  • the present invention relates to a compound of formula (IXa) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents H or Fmoc, X represents O or NH and Re represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (IXa) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents H, X represents O and Re represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (IXa) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents H, X represents O and Re represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (IXa) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents H, X represents NH and Re represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (IXa) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents Fmoc, X represents O and Re represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (IXa) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents Fmoc, X represents O and Re represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (IXa) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents Fmoc, X represents NH and Re represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (IX) for its use as a drug for the treatment of microbial infections, as defined above, having the following general formula IXb):
  • R 2 , 5 and Y are as defined above.
  • the present invention relates to a compound of formula (IXb) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents H or Fmoc, X represents O or NH and R6 represents H, C 1 -C7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (IXb) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents H, X represents O and 5 represents H, C 1 -C7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (IXb) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents H, X represents O and 5 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (IXb) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents H, X represents NH and 5 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (IXb) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents Fmoc, X represents O and Re represents H, C 1 -C7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (IXb) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents Fmoc, X represents O and Re represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (IXb) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents Fmoc, X represents NH and R6 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (IXb) for its use as a drug for the treatment of microbial infections, as defined above, having one of the following formulae:
  • the present invention relates to a compound of formula (I) for its use as a drug for the treatment of microbial infections, as defined above, having the following general formula (X):
  • R l s R 2 , Re and Y are as defined above.
  • the present invention relates to a compound of formula (IX) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents H or Fmoc, X represents O or NH and 3 ⁇ 4 represents H, C 1 -C7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (IX) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents H, X represents O and 5 represents H, C 1 -C7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (IX) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents H, X represents O and 5 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (IX) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents H, X represents NH and 5 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (IX) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents Fmoc, X represents O and 5 represents H, C 1 -C7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (IX) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents Fmoc, X represents O and 5 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (IX) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents Fmoc, X represents NH and 5 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (X) for its use as a drug for the treatment of microbial infections, as defined above, having the following general formula (Xa):
  • R 2 , Re and Y are as defined above.
  • the present invention relates to a compound of formula (Xa) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents H or Fmoc, X represents O or NH and Re represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (Xa) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents H, X represents O and Re represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (Xa) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents H, X represents O and Re represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (Xa) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents H, X represents NH and Re represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (Xa) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents Fmoc, X represents O and Re represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (Xa) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents Fmoc, X represents O and Re represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (Xa) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents Fmoc, X represents NH and Re represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (X) for its use as a drug for the treatment of microbial infections, as defined above, having the following general formula Xb):
  • R 2 , Re and Y are as defined above.
  • the present invention relates to a compound of formula (Xb) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents H or Fmoc, X represents O or NH and Re represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (Xb) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents H, X represents O and Re represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (Xb) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents H, X represents O and Re represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (Xb) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents H, X represents NH and Re represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (Xb) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents Fmoc, X represents O and Re represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (Xb) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents Fmoc, X represents O and Re represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (Xb) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents Fmoc, X represents NH and Re represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (I) for its use as a drug for the treatment of microbial infections, as defined above, having the following general formula (XI):
  • R l s R 2 , Re and Y are as defined above.
  • the present invention relates to a compound of formula (XI) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents H or Fmoc, X represents O or NH and Re represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (XI) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents H, X represents O and Re represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (XI) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents H, X represents O and Re represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (XI) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents H, X represents NH and Re represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (XI) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents Fmoc, X represents O and Re represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (XI) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents Fmoc, X represents O and Re represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (XI) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents Fmoc, X represents NH and Re represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (XI) for its use as a drug for the treatment of microbial infections, as defined above, having the following general formula (XIa):
  • R 2 , 5 and Y are as defined above.
  • the present invention relates to a compound of formula (XIa) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents H or Fmoc, X represents O or NH and 3 ⁇ 4 represents H, C 1 -C7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (XIa) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents H, X represents O and 5 represents H, C 1 -C7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (XIa) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents H, X represents O and 5 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (XIa) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents H, X represents NH and 5 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (XIa) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents Fmoc, X represents O and 5 represents H, C 1 -C7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (XIa) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents Fmoc, X represents O and Re represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (XIa) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents Fmoc, X represents NH and Re represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (XI) for its use as a drug for the treatment of microbial infections, as defined above, having the following general formula (Xlb):
  • R 2 , 5 and Y are as defined above.
  • the present invention relates to a compound of formula (Xlb) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents H or Fmoc, X represents O or NH and 3 ⁇ 4 represents H, C 1 -C7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (Xlb) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents H, X represents O and 5 represents H, C 1 -C7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (Xlb) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents H, X represents O and 5 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (Xlb) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents H, X represents NH and 5 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (Xlb) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents Fmoc, X represents O and 5 represents H, C 1 -C7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (Xlb) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents Fmoc, X represents O and Re represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (Xlb) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents Fmoc, X represents NH and Re represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (I) for its use as a drug for the treatment of microbial infections, as defined above, having the following general formula XII):
  • R l s R 2 , Re and Y are as defined above.
  • the present invention relates to a compound of formula (XII) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents H or Fmoc, X represents O or NH and Re represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (XII) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents H, X represents O and Re represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (XII) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents H, X represents O and Re represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (XII) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents H, X represents NH and Re represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (XII) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents Fmoc, X represents O and 3 ⁇ 4 represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (XII) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents Fmoc, X represents O and 5 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (XII) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents Fmoc, X represents NH and R6 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (XII) for its use as a drug for the treatment of microbial infections, as defined above, having the following general formula Xlla):
  • R 2 , 5 and Y are as defined above.
  • the present invention relates to a compound of formula (Xlla) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents H or Fmoc, X represents O or NH and 5 represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (Xlla) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents H, X represents O and 5 represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (Xlla) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents H, X represents O and 5 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (Xlla) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents H, X represents NH and 5 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (Xlla) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents Fmoc, X represents O and Re represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (Xlla) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents Fmoc, X represents O and 5 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (Xlla) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents Fmoc, X represents NH and R6 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (XII) for its use as a drug for the treatment of microbial infections, as defined above, having the following general formula Xllb):
  • R 2 , 5 and Y are as defined above.
  • the present invention relates to a compound of formula (Xllb) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents H or Fmoc, X represents O or NH and 5 represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (Xllb) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents H, X represents O and 5 represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (Xllb) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents H, X represents O and 5 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (Xllb) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents H, X represents NH and 3 ⁇ 4 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (Xllb) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents Fmoc, X represents O and 3 ⁇ 4 represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (Xllb) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents Fmoc, X represents O and R6 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (Xllb) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents Fmoc, X represents NH and 5 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (I) for its use as a drug for the treatment of microbial infections, as defined above, having the following neral formula (XIII):
  • R l s R 2 , 5 and Y are as defined above.
  • the present invention relates to a compound of formula (XIII) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents H or Fmoc, X represents O or NH and 5 represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (XIII) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents H, X represents O and 5 represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (XIII) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents H, X represents O and 5 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (XIII) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents H, X represents NH and Re represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (XIII) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents Fmoc, X represents O and Re represents H, C 1 -C7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (XIII) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents Fmoc, X represents O and R6 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (XIII) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents Fmoc, X represents NH and 5 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (XIII) for its use as a drug for the treatment of microbial infections, as defined above, having the following general formula (Xllla):
  • the present invention relates to a compound of formula (Xllla) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents H or Fmoc, X represents O or NH and 5 represents H, C 1 -C7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (Xllla) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents H, X represents O and 5 represents H, C 1 -C7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (Xllla) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents H, X represents O and Re represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (Xllla) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents H, X represents NH and Re represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (Xllla) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents Fmoc, X represents O and R6 represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (Xllla) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents Fmoc, X represents O and 5 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (Xllla) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents Fmoc, X represents NH and 5 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (XIII) for its use as a drug for the treatment of microbial infections, as defined above, having the following general formula (Xlllb):
  • R 2 , 5 and Y are as defined above.
  • the present invention relates to a compound of formula (Xlllb) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents H or Fmoc, X represents O or NH and 5 represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (Xlllb) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents H, X represents O and Re represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (Xlllb) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents H, X represents O and Re represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (Xlllb) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents H, X represents NH and R6 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (Xlllb) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents Fmoc, X represents O and 5 represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (Xlllb) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents Fmoc, X represents O and 5 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (Xlllb) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents Fmoc, X represents NH and 5 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (I) for its use as a drug for the treatment of microbial infections, as define above, having the following general formu
  • R l s R 2 , 5 and Y are as defined above.
  • the present invention relates to a compound of formula (XIV) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents H or Fmoc, X represents O or NH and 3 ⁇ 4 represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (XIV) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents H, X represents O and R6 represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (XIV) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents H, X represents O and Re represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (XIV) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents H, X represents NH and 5 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (XIV) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents Fmoc, X represents O and 5 represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (XIV) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents Fmoc, X represents O and 5 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (XIV) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents Fmoc, X represents NH and 5 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (XIV) for its use as a drug for the treatment of microbial infections, as defined above, having the following general formula (XI Va):
  • the present invention relates to a compound of formula (XIV a) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents H or Fmoc, X represents O or NH and Re represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (XlVa) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents H, X represents O and 5 represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (XIV a) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents H, X represents O and R6 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (XIV a) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents H, X represents NH and 5 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (XIV a) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents Fmoc, X represents O and 5 represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (XIV a) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents Fmoc, X represents O and 5 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (XIV a) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents Fmoc, X represents NH and 5 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (XIV) for its use as a drug for the treatment of microbial infections, as defined above, having the following general formula (XI Vb):
  • R 2 , Re and Y are as defined above.
  • the present invention relates to a compound of formula (XlVb) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents H or Fmoc, X represents O or NH and Re represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (XlVb) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents H, X represents O and R6 represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (XlVb) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents H, X represents O and 5 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (XlVb) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents H, X represents NH and 5 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (XlVb) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents Fmoc, X represents O and 5 represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (XlVb) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents Fmoc, X represents O and 5 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (XlVb) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents Fmoc, X represents NH and Re represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (I) for its use as a drug for the treatment of microbial infections, as defined above, having the following general formula (XV):
  • R l s R 2 , 5 and Y are as defined above.
  • the present invention relates to a compound of formula (XV) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents H or Fmoc, X represents O or NH and 3 ⁇ 4 represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (XV) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents H, X represents O and 5 represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (XV) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents H, X represents O and 5 represents CH 3 or a benzyl group, and in particular F, G, I, J represent a hydrogen atom and H represents tBu or CF 3 .
  • the present invention relates to a compound of formula (XV) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents H, X represents NH and R 6 represents CH 3 or a benzyl group, and in particular F, G, I, J represent a hydrogen atom and H represents tBu or CF 3 .
  • the present invention relates to a compound of formula (XV) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents Fmoc, X represents O and 5 represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (XV) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents Fmoc, X represents O and 3 ⁇ 4 represents CH 3 or a benzyl group, and in particular F, G, I, J represent a hydrogen atom and H represents tBu or CF 3 .
  • the present invention relates to a compound of formula (XV) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents Fmoc, X represents NH and R6 represents CH 3 or a benzyl group, and in particular F, G, I, J represent a hydrogen atom and H represents tBu or CF 3 .
  • the present invention relates to a compound of formula (XV) for its use as a drug for the treatment of microbial infections, as defined above, having the following neral formula (XVa):
  • R 2 , Re and Y are as defined above.
  • the present invention relates to a compound of formula (XVa) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents H or Fmoc, X represents O or NH and 3 ⁇ 4 represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (XVa) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents H, X represents O and 5 represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (XVa) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents H, X represents O and 5 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (XVa) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents H, X represents NH and 5 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (XVa) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents Fmoc, X represents O and 5 represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (XVa) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents Fmoc, X represents O and Re represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (XVa) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents Fmoc, X represents NH and Re represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (XV) for its use as a drug for the treatment of microbial infections, as defined above, having the following general formula (XVb):
  • R 2 , 5 and Y are as defined above.
  • the present invention relates to a compound of formula (XVb) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents H or Fmoc, X represents O or NH and 3 ⁇ 4 represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (XVb) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents H, X represents O and 5 represents H, C 1 -C 7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (XVb) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents H, X represents O and 5 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (XVb) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents H, X represents NH and 5 represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (XVb) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents Fmoc, X represents O and Re represents H, C1-C7 alkyl or a benzyl group.
  • the present invention relates to a compound of formula (XVb) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents Fmoc, X represents O and Re represents CH 3 or a benzyl group.
  • the present invention relates to a compound of formula (XVb) for its use as a drug for the treatment of microbial infections, as defined above, wherein R 2 represents Fmoc, X represents NH and R6 represents CH 3 or a benzyl group.
  • the present invention relates to a compound for its use as a drug for the treatment of microbial infections, having one of the formula (I) to (XV), as defined above, wherein said compound is liable to be administered by oral route at a unit dose comprised from 100 mg to 1,500 mg, in particular from 100 mg to 1,000 mg, in particular from 100 to 500 mg.
  • Said pharmaceutical composition can be administered 2 or 3 times per day.
  • the present invention relates to a compound for its use as a drug for the treatment of microbial infections, having one of the formula (I) to (XV), under a form liable to be administrable by intraveinous route at a dose comprised from 0,1 mg to 1000 mg, in particular from 10 mg to 1,000 mg, in particular from 10 to 500 mg, in particular from 10 to 100 mg.
  • Said pharmaceutical composition can be administered 2 or 3 times per day.
  • the present invention relates to a compound, for its use as a drug for the treatment of microbial infections, having one of the formula (I) to (XV), as defined above, administrable by oral route at a dose comprised from about 10 mg/kg to about 200 mg/kg.
  • the present invention relates to a compound, for its use as a drug for the treatment of microbial infections, having one of the formula (I) to (XV), as defined above, administrable by intraveinous route at a dose comprised from about 5 ⁇ g/kg to about 50 mg/kg.
  • the present invention relates to a compound of formula (I) to (XV) such as defined above, for its use in anti-bio film surface treatment.
  • the present invention relates to a compound of formula (I) to (XV) such as defined above, for its use in anti-biofilm treatment of the surface of submerged structures, in particular submerged marine structures.
  • the present invention relates to a compound of formula (I) to (XV) such as defined above, for its use in anti-biofilm treatment of the surface of medical devices.
  • said compound of formula (I) to (XV) such as defined above is grafted onto the surface to treat. Grafting can be performed by a method known by the one skilled in the art.
  • the present invention relates to a compound of formula (I) to (XV) such as defined above, for its use in drug vectorization.
  • the present invention also relates to a compound of formula (I) to (XV) such as defined above, for its use in the preparation of a vector peptide.
  • the present invention relates to a compound of formula (I) to (XV) such as defined above, having one of the following formulae:
  • the present invention relates to a compound of formula (I) to (XV) such as defined above, having one of the following formulae:
  • the present invention relates to a pharmaceutical composition
  • a pharmaceutical composition comprising a compound of formula (I) to (XV) such as defined above, in association with a pharmaceutically acceptable vehicle.
  • the present invention relates to a pharmaceutical composition
  • a pharmaceutical composition comprising a compound of formula (I) to (XV) such as defined above, in association with a pharmaceutically acceptable vehicle.
  • pharmaceutically acceptable vehicle denotes in particular cellulose, starch, benzyl alcohol, polyethylene glycol, gelatin, lactose, polysorbate, magnesium or calcium stearate, xanthan gum, guar, alginate, colloidal silica.
  • compositions according to the invention can be used by oral, parenteral, topic, or rectal route or in aerosols.
  • compositions for oral administration tablets, pills, gelatin capsules, powders or granules can be used.
  • the active ingredient according to the invention is mixed with one or more inert diluents or adjuvants, such as saccharose, lactose or starch.
  • these compositions can comprise substances other than the diluents, for example a lubricant such as magnesium stearate or a coating intended for controlled release.
  • compositions for oral administration pharmaceutically acceptable solutions, suspensions, emulsions, syrups and elixirs containing inert diluents such as water or paraffin oil can be used.
  • inert diluents such as water or paraffin oil
  • These compositions can also comprise substances other than the diluents, for example wetting products, sweeteners or flavourings.
  • compositions for parenteral administration can be sterile solutions or emulsions.
  • solvent or vehicle water, propylene glycol, a polyethylene glycol, vegetable oils, in particular olive oil, injectable organic esters, for example ethyl oleate can be used.
  • These compositions can also contain adjuvants, in particular wetting agents, isotoning agents, emulsifiers, dispersants and stabilizers.
  • the sterilization can be carried out in several ways, for example using a bacteriological filter, by irradiation or by heating. They can also be prepared in the form of sterile solid compositions which can be dissolved at the moment of use in sterile water or any other injectable sterile medium.
  • compositions for topical administration can be for example creams, ointments, lotions or aerosols.
  • compositions for rectal administration are suppositories or rectal capsules, which, in addition to the active ingredient, contain excipients such as cocoa butter, semi-synthetic glycerides or polyethylene glycols.
  • compositions can also be aerosols.
  • the compositions can be stable sterile solutions or solid compositions dissolved at the moment of use in pyrogen-free sterile water, in serum or any other pharmaceutically acceptable vehicle.
  • the active ingredient is finely divided and combined with a diluent or hydrosoluble solid vehicle, for example dextran, mannitol or lactose.
  • a pharmaceutical composition as defined above comprising one of the following compounds:
  • the present invention relates to a pharmaceutical composition as defined above, comprising one of the following compounds:
  • the present invention relates to a pharmaceutical composition
  • a pharmaceutical composition comprising:
  • antibiotic compound in particular from the family of the fluoroquinolones, such as ciprofloxacin, norfloxacin, pefloxacin, enofloxacin, ofloxacin, levofloxacin and moxifloxacin, in combination with a pharmaceutically acceptable vehicle.
  • the present invention relates to a pharmaceutical composition
  • a pharmaceutical composition comprising:
  • antibiotic compound in particular from the family of the fluoroquinolones, such as ciprofloxacin, norfloxacin, pefloxacin, enofloxacin, ofloxacin, levofloxacin and moxifloxacin, in combination with a pharmaceutically acceptable vehicle, and provided that the following compounds are excluded:
  • the present invention relates to a pharmaceutical composition
  • a pharmaceutical composition comprising at least one compound of formula (I) to (XV) and at least one antibiotic compound, as defined above,
  • weight proportion of said compound is comprised from 15% to 85% and the weight proportion of said antibiotic compound is comprised from 15% to 85%.
  • the pharmaceutical composition of the invention as defined above comprises approximately 350 to approximately 2,000 mg, preferably approximately 1,000 to approximately 1,500 mg, of compound of formula (I) according to the invention in 1 to 4 administrations per day and approximately 350 to approximately 2,000 mg, preferably approximately 1,000 to approximately 1,500 mg, of antibiotic compound, in particular of the family of the fluoroquinolones, such as ciprofloxacin in 1 to 4 administrations per day, preferably in 2 administrations per day.
  • the present invention relates to products comprising:
  • the present invention relates to products comprising:
  • antibiotic compound in particular from the family of the fluoroquinolones, such as ciprofloxacin, norfloxacin, pefloxacin, enofloxacin, ofloxacin, levofloxacin and moxifloxacin,
  • the pharmaceutical composition of the invention as defined above comprises approximately 350 to approximately 2,000 mg, preferably approximately 1,000 to approximately 1,500 mg, of compound of formula (I) according to the invention in 1 to 4 administrations per day and approximately 350 to approximately 2,000 mg, preferably approximately 1,000 to approximately 1,500 mg, of antibiotic compound, in particular of the family of the fluoroquinolones, such as ciprofloxacin in 1 to 4 administrations per day, preferably in 2 administrations per day.
  • the present invention relates to a cosmetic composition
  • a cosmetic composition comprising a compound of formula (I) to (XV) such as defined above, in association with a cosmetically acceptable vehicle.
  • cosmetically acceptable vehicle denotes in particular a vehicle suitable for use in contact with human and animal cells, in particular cells of the epidermis, without toxicity, irritation, allergic response and the like.
  • Said cosmetic compositions are for example solutions, such as lotions, liquid or semi- liquid emulsions, such as milks, or emulsions of soft consistency such as creams or gels, obtained by dispersion of a fatty phase in an aqueous phase, or conversely liquid, semi-soft or liquid suspensions, ointments, powders or aerosols.
  • compositions can be stable sterile solutions or solid compositions dissolved at the moment of use in pyrogen-free sterile water, in serum or any other pharmaceutically acceptable vehicle.
  • said cosmetic composition is a toothpaste or a hair lotion.
  • compositions are adapted and prepared according to conventional methods known to those skilled in the art.
  • cosmetically acceptable vehicles can be mentioned surfactants, dyes, fragrances, preservatives, emulsifiers, emulsion stabilizers, emollients, moisturizers, natural or synthetic waxes, thickeners and / or gelling agents, humectants, liquid carriers such as water, fatty substances such as natural or synthetic oils designed to form the fatty phase milks or creams, and mixtures thereof.
  • the present invention relates to a cosmetic composition as defined above, comprising one of the following compounds:
  • the present invention relates to a cosmetic composition as defined above, comprising one of the following compounds:
  • Methyl 2-cyanoacetate [10 g (100 mmol)] was first mixed with acrylonitrile [11.66 g (220 mmol)]. Then, triethylamine [5.05 g (50 mmol)] was added, followed by lithium perchlorate [5.32 g (50 mmol)]. The reaction was stirred continuously and allowed to react overnight. After confirming completion of the reaction by TLC, the product was extracted with ethyl acetate. The organic layer was washed with 5% citric acid solution and brine, dried over magnesium sulfate, filtered and evaporated. The product precipitated overnight, and the crystals were filtered with a minimum AcOEt as yellow pale powder. (12.6 g, 61 mmol, 61% yield)
  • Methyl 2-cyano-4-(Boc)amine-2-(3-(Boc)amine propyl)pentanoate [2.3 g (5.6mmol)] was dissolved in methanol [125mL].
  • a solution of sodium hydroxide in water (2M) (12.5 mL, 25 mmol) and Raney nickel were added and the mixture was stirred at room temperature for 7 days under 5 bar H 2 pressure.
  • the reaction mixture was filtered through a celite pad to remove Raney nickel before evaporation to dryness.
  • the crude mixture was dissolved in a 5:5 mixture of tetrahydroiuran and water.
  • DDCCCC [[110099 mmgg ((00..5533mmmmooll))]],, HHOOBBtt [[7722 mmgg ((00..5533mmmmooll))]],, DDMMAAPP [[55 mmgg ((00..0055mmmmooll))]] aanndd tteettrraaddeeccyyllaammiinnee[[ll 1133 mmgg ((00..5533 mmmmooll))]] wweerree aaddddeedd..
  • MMSS--EESSII++ : ccaallccdd ffoorr CC4488HH7766NN44OO77 882200..55771144,, ffoouunndd 884433..55660066 [[MM++NNaa]] ++
  • Methyl-3,6-bis((tert-butoxycarbonyl)amino)-3-(3-((tert- butoxycarbonyl)amino)propyl)hexanoate [0.130 g (0.25 mmol)] was dissolved in a 1 : 1 mixture of THF and H 2 0. LiOH [0.012 g (0.5 mmol)] was added and the reaction mixture was stirred at rt for 5 days. The product was used in following synthesis without any further purification. (0.120 g, 0.24 mmol, 98% yield).
  • Boc-protected ⁇ -peptidomimetic was deprotected by dissolving it in DCM (-0.4 M) and adding an equivalent volume of TFA:TIS: water (95:2.5:2.5). The mixture was stirred at rt for 2 h before it was evaporated to dryness.
  • a secondary deprotection can be made with piperidine/DCM (20/80). The mixture was stirred at rt for 2 h before it was evaporated to dryness.
  • the crude product was purified by preparative RP- HPLC. The purity of the pure ⁇ -peptidomimetics was checked by analytical RP-HPLC before the residue was lyophilized. All compounds possessed purity above 95%.
  • HMBA-AM resin 100-200 mesh (leq) was initially washed five times with DMF, DCM and DMF, then allowed to swell in DMF for 30 min.
  • Fmoc-Tbt-OH 4eq was dissolved in dry DCM.
  • the solution was cooled to 0 °C before DIC (4eq) was added.
  • the reaction was stirred for 20 min before the solvent was removed in vacuo.
  • the resulting symmetrical anhydride was redissolved in DMF before adding directly to the resin.
  • a solution of DMAP (O. leq) in DMF was added and the resin shaken for 1 h before washing with DMF, DCM and DMF.
  • Fmoc removal was performed by using 20% (v:v) piperidine in DMF3 times for 5 min. The resin was washed five times with DMF. Stepwise couplings were accomplished with 2 equivalents of protected- PbisOrn(Boc) 2 OH, 2 equivalents of HATU and 4 equivalents of DIEA. Coupling reaction with Fmocp 2 bisOrn(Boc) 2 OH was allowed to proceed for 16h twice at 50°C and coupling reaction with Bocp 3 bisOrn(Boc) 2 OH was allowed to proceed for 2h at room temperature.All protected amino acids and reagents were dissolved in DMF at 0.15 M. After desired time, the solution was removed by filtration and the resin was washed with DMF five times.
  • the Minimal Inhibitory Concentration (MIC in ⁇ g/mL) of the compounds of the invention has been determined over six bacterial strains (three Gram positive: S. aureus ATCC25923 ATCC25923, S. aureus 1199B and E. faecalis ATCC29212; and three Gram negative strains: E. coli ATCC25922 , P. aeruginosa ATCC27853 and A. baumannii ATCC 19606) according to Synthetic Antimicrobial Peptidomimetics with Therapeutic Potential (Bengt Erik Haug, Wenche Stensen, Manar Kalaaji, 0ystein Rekdal, and John S. Svendsen, J. Med. Chem. 2008, 51, 4306-4314).
  • RTbtR-NH 2 represents the following structure:
  • the antibacterial activities of the peptides were investigated by measurement of the Minimal Inhibitory Concentration (MIC) over six species of bacteria, three gram positive strains, Staphylococcus aureus ATCC25923, Enterrococcus faecalis ATCC29212, and the methicillin resistant Staphylococcus aureus SA-1199B, and three Gram negative bacterial strains, Escherichia coli ATCC25922, Pseudomonas aeruginosa ATCC29853 and Acinetobacter baumannii ATCC 19606.
  • MIC Minimal Inhibitory Concentration
  • the new AMP must be selective to bacteria over mammalian cells.
  • the cytotoxicity of the compounds of the invention against two types of human cells, Jurkat and SHSYS5 were evaluated (Delaroche D. et al, Anal. Chem. (2007), 79(5): 1932-8).
  • Incubation HB265 corresponds to the following structure:

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Abstract

La présente invention concerne de nouveaux acides aminés cationiques, des compositions pharmaceutiques les contenant et leur utilisation pour le traitement d'infections bactériennes.
PCT/IB2013/001772 2013-05-27 2013-05-27 Nouveaux acides aminés cationiques, compositions pharmaceutiques les contenant et leur utilisation pour le traitement d'infections bactériennes WO2014191789A1 (fr)

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