Antibacterial agents, compositions and uses thereof

Abstract

Isocyanobenzoate or isocyanobenzamide compounds of formula (I): able to act as Gram-positive antimicrobial agents, in particular against several strains of Staphylococcus aureus, therapeutic uses and pharmaceutical compositions thereof.

Description

[0001]“Antibacterial agents, compositions and uses thereof” *** Field of the invention This disclosure concerns compounds having antibacterial activity against pathogenic Gram-positive bacteria, compositions and uses thereof. Background of the invention Antimicrobial resistance is a growing issue worldwide, with no treatment options available for some pathogen strains. This is increasing the number of casualties and could have a terrible impact on the global population. For example, it has been predicted that multi-resistant bacteria could cause up to 10 million deaths each year globally by 2050, becoming the second leading cause of death. Gram-positive Staphylococcus aureus is particularly concerning, as it causes nosocomial infections and is among the leading causes of death in hospitalized patients. Methicillin- resistant S. aureus (MRSA) strains are a serious public health concern, with strains such as MU50 (ATCC 700699) being resistant not only to beta-lactam antibiotics but also to vancomycin, the antibiotic of last resort for physicians. For this reason, to combat the emerging virulence of bacteria that can escape the action of classic antibiotics, innovative antibacterial agents must be identified. Summary of the invention The object of this disclosure is to provide new compounds that exhibit antibacterial activity against pathogenic Gram-positive bacteria. According to the invention, the above object is achieved thanks to the subject matter recalled specifically in the ensuing claims, which are understood as forming an integral part of this disclosure. The present invention provides a family of compounds containing an isocyanobenzoate or isocyanobenzamide moiety pivotal for imparting a strong antibacterial activity. An embodiment of the present disclosure concerns a compound of formula (I): wherein A is -NR- or -O-; R is selected from H, C1-8alkyl, substituted or unsubstituted Ar6, substituted or unsubstituted (CH2)l-Ar6; B is selected from H, C1-8alkyl, C3-6cycloalkyl, Ar1, and (CH2)n-Ar1; C is selected from a substituted or unsubstituted C1-16alkyl, substituted or unsubstituted C3-10cycloalkyl, substituted or unsubstituted Ar2, and substituted or unsubstituted (CH2)m-Ar2, adamantane; D1, D2, D3and D4are independently selected from - H, -CH3,-Cl, and -CF3; n is an integer 1 to 4; m is an integer 1 to 4; l is an integer 1 to 4; Ar1, Ar2and Ar6are independently selected from aryl and heteroaryl; provided that the compound of formula (I) is not . The present invention also concerns pharmaceutical compositions and medical uses of the compounds of formula (I) in the treatment of pathological conditions associated to infections of Gram-positive pathogenic bacteria. BRIEF DESCRIPTION OF THE DRAWINGS The invention will now be described, by way of example only, with reference to the enclosed figures of drawing, wherein: - Figure 1: Time-kill assay of compounds 16 and 35 against MRSA ATCC 33592. - Figure 2: Metabolic activity of biofilms grown in the presence of compounds 16, 20, 24, 29, 30 and 32. - Figure 3: Cell Viability assay (MTT test). Detailed description of the invention In the following description, numerous specific details are given to provide a thorough understanding of embodiments. The embodiments can be practiced without one or more of the specific details, or with other methods, components, materials, etc. In other instances, well-known structures, materials, or operations are not shown or described in detail to avoid obscuring aspects of the embodiments. Reference throughout this specification to “one embodiment” or “an embodiment” means that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment. Thus, the appearances of the phrases “in one embodiment” or “in an embodiment” in various places throughout this specification are not necessarily all referring to the same embodiment. Furthermore, the particular features, structures, or characteristics may be combined in any suitable manner in one or more embodiments. The headings provided herein are for convenience only and do not interpret the scope or meaning of the embodiments. The term "C1-12 alkyl" is understood as a straight or branched chain of 1-12 carbon atoms containing only single bonds between adjacent carbon atoms. Preferably, the C1-12 alkyl group is selected from methyl, ethyl, propyl, iso-propyl, butyl and its isomers, pentyl and its isomers, hexyl and its isomers. The term "C2-10 alkenyl" is understood as a straight or branched chain of 2-10 carbon atoms containing at least one double bond between adjacent carbon atoms. Alkenyls include cis and trans isomers. Preferably, the C2-10 alkenyl group is selected from ethylenyl, propylenyl, 1-butenyl, 2-butenyl, isobutenyl, 1-pentenyl, 2-pentenyl, 3-methyl-1-butenyl, 2-methyl-2-butenyl, 2,3-dimethyl-2-butenyl. The term "C2-6 alkynyl" is understood as a straight or branched chain of 2-6 carbon atoms containing at least one triple bond between adjacent carbon atoms. Preferably, the C2-6 alkynyl group is selected from ethynyl, propynyl, pentynyl, and their isomers. The term "C1-6 alkoxy" is understood as a straight or branched alkyl chain of 1-6 carbon atoms containing one oxygen atom. Preferably, the C1-6 alkoxy group is selected from methoxy, ethoxy, propoxy, pentoxy and their isomers. The term "Cx-y cycloalkyl" is understood as a cyclic hydrocarbon group having x-y carbon atoms. Preferably, the Cx-y cycloalkyl group is selected from cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl. The term "aryl" is understood as an aromatic ring. Preferably the aryl group is selected from benzene, substituted benzene, naphthalene, biphenyl, 1,2,3,4- tetrahydronaphthalene. The term "heteroaryl" is understood as aromatic heterocyclic compounds in which one and more carbon atom(s) of the molecule's skeleton has been replaced by an atom other than carbon. Typical heteroatoms include nitrogen, oxygen, and sulfur. Preferably, the heteroaryl is selected from pyridine, pyrimidine, furan, thiophene, indole, quinoline, isoquinoline. In one embodiment, the present invention concerns wherein A is -NR- or -O-; R is selected from H, C1-8alkyl, substituted or unsubstituted Ar6, substituted or unsubstituted (CH2)lAr6; B is selected from H, C1-8alkyl, C3-6cycloalkyl, Ar1, and (CH2)n-Ar1; C is selected from a substituted or unsubstituted C1-16alkyl, substituted or unsubstituted C3-10cycloalkyl, substituted or unsubstituted Ar2, and substituted or unsubstituted (CH2)m-Ar2, adamantane; D1, D2, D3and D4are independently selected from - H, -CH3,-Cl, and -CF3; n is an integer 1 to 4; m is an integer 1 to 4; l is an integer 1 to 4; Ar1, Ar2and Ar6are independently selected from aryl and heteroaryl; provided that the compound of formula (I) is not . In an embodiment, Ar1, and Ar2independently selected from benzene, naphthalene, thiophene, pyridine, biphenyl, 1,2,3,4-tetrahydronaphthalene. In an embodiment, Ar6is selected from benzene, pyridine, furan, thiophene. In one embodiment, when R is a substituted Ar6, or a substituted (CH2)lAr6, the one or more substituents are independently selected from halogens, -OH, -OCH3, - NO2, methyl, -NH2. In one embodiment, R is selected from H, C1-6alkyl, benzene. In one embodiment, B is selected from H, C1-4alkyl, benzene, (CH2)1-4-benzene. In one embodiment, when C is a substituted C1-16alkyl, a substituted C3-10cycloalkyl, a substituted Ar2, or a substituted (CH2)m-Ar2, the one or more substituents are selected from halogens, CF3, C1-6alkyl, C1-6alkoxy, C2-6alkynyl, C3-6cycloalkyl, benzene. Preferably the one or more substituents are selected from methyl, ethyl, propyl, butyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl. In one embodiment, C is selected from C1-12alkyl, C3-7cycloalkyl, tetrahydronaphtalene, benzene, naphthalene, and adamantane, optionally substituted with one or more substituents as defined above. In one embodiment, the compound of formula (I) is selected from: 2-(tert-butylamino)-2-oxo-1-phenylethyl 4- isocyanobenzoate, N-benzyl-N-(2-(tert-butylamino)-2- oxoethyl)-4-isocyanobenzamide, 2-(tert-butylamino)-2- oxoethyl 4-isocyanobenzoate, 2-(benzylamino)-2-oxoethyl 4-isocyanobenzoate, 1-(tert-butylamino)-3-methyl-1- oxobutan-2-yl 4-isocyanobenzoate, 2-oxo-2- (phenethylamino)ethyl 4-isocyanobenzoate, 1- (benzylamino)-3-methyl-1-oxobutan-2-yl 4- isocyanobenzoate, 2-(dodecylamino)-2-oxo-1-phenylethyl 4-isocyanobenzoate, N-butyl-N-(2-(cyclohexylamino)-2- oxoethyl)-4-isocyanobenzamide, N-(2-(cyclohexylamino)- 2-oxo-1-phenylethyl)-4-isocyano-N-phenylbenzamide, N- (2-(dodecylamino)-2-oxo-1-phenylethyl)-4-isocyano-N- phenylbenzamide, N-butyl-N-(2-(cyclohexylamino)-2-oxo- 1-phenylethyl)-4-isocyanobenzamide, N-(2-(tert- butylamino)-2-oxo-1-phenylethyl)-4-isocyano-N-(4- methoxyphenyl)benzamide, 2-(adamantan-1-ylamino)-2- oxoethyl 4-isocyanobenzoate, N-(2-(adamantan-1- ylamino)-2-oxo-1-phenylethyl)-4-isocyano-N- phenylbenzamide, 2-(cyclohexylamino)-2-oxoethyl 4- isocyanobenzoate, N-(2-(cyclohexylamino)-2-oxoethyl)-4- isocyanobenzamide, 2-(cycloheptylamino)-2-oxoethyl 4- isocyanobenzoate, 2-oxo-2-((1,2,3,4- tetrahydronaphthalen-1-yl)amino)ethyl 4- isocyanobenzoate, 2-oxo-2-(phenylamino)ethyl 4- isocyanobenzoate, 2-(cyclopentylamino)-2-oxoethyl 4- isocyanobenzoate, 2-(benzhydrylamino)-2-oxoethyl 4- isocyanobenzoate, 2-(butylamino)-2-oxoethyl 4- isocyanobenzoate, 2-oxo-2-((5,6,7,8- tetrahydronaphthalen-1-yl)amino)ethyl 4- isocyanobenzoate, 2-(isopropylamino)-2-oxoethyl 4- isocyanobenzoate, 2-((2,6-dimethylphenyl)amino)-2- oxoethyl 4-isocyanobenzoate, 2-oxo-2-(o- tolylamino)ethyl 4-isocyanobenzoate, 2-((4- methoxyphenyl)amino)-2-oxoethyl 4-isocyanobenzoate, 2- ((3,4-dimethoxyphenyl)amino)-2-oxoethyl 4- isocyanobenzoate, 2-((2-chlorophenyl)amino)-2-oxoethyl 4-isocyanobenzoate, 2-((4-chlorophenyl)amino)-2- oxoethyl 4-isocyanobenzoate, 2-(naphthalen-1-ylamino)- 2-oxoethyl 4-isocyanobenzoate, 2-([1,1'-biphenyl]-4- ylamino)-2-oxoethyl 4-isocyanobenzoate, 2-((3- ethynylphenyl)amino)-2-oxoethyl 4-isocyanobenzoate, 2- ((3-fluorophenyl)amino)-2-oxoethyl 4-isocyanobenzoate, 2-((2-methoxyphenyl)amino)-2-oxoethyl 4- isocyanobenzoate, 2-((3-chlorophenyl)amino)-2-oxoethyl 4-isocyanobenzoate, 2-((2,3-dichlorophenyl)amino)-2- oxoethyl 4-isocyanobenzoate, 2-((2- ethynylphenyl)amino)-2-oxoethyl 4-isocyanobenzoate, 4- isocyano-N-(2-oxo-2-(phenylamino)ethyl)benzamide, 2- ((4-ethynylphenyl)amino)-2-oxoethyl 4-isocyanobenzoate, 2-((2-fluorophenyl)amino)-2-oxoethyl 4- isocyanobenzoate, 2-oxo-2-((2- (trifluoromethyl)phenyl)amino)ethyl 4-isocyanobenzoate. In one embodiment, the compound of formula (I) is selected from: 2-(adamantan-1-ylamino)-2-oxoethyl 4- isocyanobenzoate; 2-(cyclohexylamino)-2-oxoethyl 4- isocyanobenzoate; N-(2-(cyclohexylamino)-2-oxoethyl)-4- isocyanobenzamide; 2-oxo-2-((1,2,3,4- tetrahydronaphthalen-1-yl)amino)ethyl 4- isocyanobenzoate; 2-oxo-2-(phenylamino)ethyl 4- isocyanobenzoate; 2-oxo-2-((5,6,7,8- tetrahydronaphthalen-1-yl)amino)ethyl 4- isocyanobenzoate; 2-((4-methoxyphenyl)amino)-2-oxoethyl 4-isocyanobenzoate; 2-((2-chlorophenyl)amino)-2- oxoethyl 4-isocyanobenzoate; 2-((4-chlorophenyl)amino)- 2-oxoethyl 4-isocyanobenzoate; 2-((3- fluorophenyl)amino)-2-oxoethyl 4-isocyanobenzoate; 2- ((2-methoxyphenyl)amino)-2-oxoethyl 4-isocyanobenzoate; 2-((3-chlorophenyl)amino)-2-oxoethyl 4- isocyanobenzoate; 4-isocyano-N-(2-oxo-2- (phenylamino)ethyl)benzamide; 2-((2- fluorophenyl)amino)-2-oxoethyl 4-isocyanobenzoate; 2- oxo-2-(phenylamino)ethyl 4-isocyano-2,6- dimethylbenzoate; 2-((2-chlorophenyl)amino)-2-oxoethyl 4-isocyano-2,6-dimethylbenzoate; 2-(cyclohexylamino)-2- oxoethyl 4-isocyano-2,6-dimethylbenzoate; 2-((2- fluorophenyl)amino)-2-oxoethyl 4-isocyano-2,6- dimethylbenzoate. In one embodiment, the present invention relates to a compound of formula (I) for use in the treatment of pathological conditions associated with an infection of Gram-positive pathogenic bacteria D4have the meaning set forth above. In one embodiment, the pathological conditions associated with infection of Gram-positive pathogenic bacteria are represented by: skin and soft tissue infections, impetigo, folliculitis, boils (furuncles), abscesses, toxic shock syndrome, septicemia, pneumonia, endocarditis, osteomyelitis, wound infections, empyema, erysipelas, septic arthritis, gastrointestinal infections, scalded skin syndrome, toxic epidermal necrolysis, nasal carriage of methicillin resistant Staphylococcus aureus. In one embodiment, the Gram-positive bacteria that are sensible to the compounds of formula (I) are: Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes, Clostridium botulinum, Clostridium tetani, Listeria monocytogenes, Bacillus anthracis, Staphylococcus epidermidis, Bacillus subtilis, Corynebacterium diphtheriae, Enterococcus faecalis, Nocardia asteroids. In one embodiment, the present invention relates to a pharmaceutical composition comprising at least one compound of formula (I) and a pharmaceutically acceptable carrier wherein A, B, C, D1, D2, D3and D4have the meaning set forth above. In one embodiment, the pharmaceutical composition can further comprise one or more additional therapeutic agents. In one embodiment, the present invention relates to a pharmaceutical composition comprising at least one compound of formula (I) and a pharmaceutically acceptable carrier for use in the treatment of pathological conditions associated with infection of Gram-positive pathogenic bacteria wherein A, B, C, D1, D2, D3and D4have the meaning set forth above. By using phenotypic screening, it has been recognized the isocyanophenyl moiety as a fundamental warhead motif of the compounds of formula (I) for the antibacterial activity. On the other hand, the remaining part of the molecule plays a pivotal role both in increasing the activity of the compounds of formula (I) and in conferring precise pharmacokinetic properties to the compounds. The compounds of the present disclosure are potent antibacterial agents with a MIC99between 0.2-0.05 μM against the most important pathogenic strains of Gram- positive bacteria. A nontoxic profile on mammalian cells completes the drug-likeness features of this class of compounds. Compounds of formula (I) herein described are useful for the treatment of disease condition by way of topical and systemic administration depending on the pathogenic Gram-positive infections to be treated. Compounds of formula (I) can be administered in various routes appropriate to the condition to be treated. Suitable routes include oral, parenteral (including subcutaneous, intramuscular, intravenous, intraarterial, intradermal, intrathecal and epidural), transdermal, rectal, nasal, topical, vaginal, intraperitoneal. When the compound is administered orally, due to the hydrolytic instability of the isocyano group when the pH is less than 5, the compound has to be formulated as gastric resistant pills, tablets, capsules. The dosage depends on a variety of factors including the age, weight and condition of the patient and the route of administration. Although daily dosage can vary from one individual to another, the compound / s will be administered to an adult human in a range of 0.0001-50 mg / kg of body weight as daily single dose or 0.01 to 1 mg / kg as daily repeated doses. Compounds of formula (I) can be formulated as a pharmaceutical composition in the form of tablet, capsule, aqueous solution, granule, powder, suspension, cream, syrup, gel, emulsion, etc. Tablets contain the compound / s of formula (I) in a mixture with non-toxic pharmaceutically excipients suitable for the manufacture of tablets. Exemplary excipients could be: inert diluents, such as sodium carbonated, lactose, dextrose, cellulose etc.; granulating and disintegrating agents as maize starch, glycolate, alginic acid; binding agents as gelatin or acacia; lubricating agents, for example silica magnesium or calcium stearate, stearic acid or talc. For preparing suppositories, a mixture of for example fatty acid glycerides or cocoa butter is first melted and the compound / s of formula (I) is / are dissolved homogenously by stirring. The homogenous mixture is then cooled into convenient sized molds. Liquid preparations, which include solutions, suspensions, and emulsions, contain the formula (I) compound / s in a mixture of excipients suitable for the manufacture of aqueous suspension such as sodium carboxymethylcellulose, methylcellulose, resin, sodium alginate and natural or synthetic gums. Eventually the liquid preparation may contain suitable colorants, flavors, stabilizers, preservatives, and thickening agents as desired. These compounds can be used to treat systemic infections. Preferred 2-aryl(alkyl)-2-oxoethyl-4- isocyanobenzoates or 4-isocyano-N-(2- (alkyl(aryl)amino)-2-oxoethyl)benzamides compounds of formula (I) are shown in Table 1. Table 1 Synthesis of compounds of formula (I) The following schemes show the general method for preparing some preferred compounds of the present description. For a more detailed description of the individual reaction steps, see the Examples herein below. Those skilled in the art will appreciate that other synthetic routes may be used to synthesize the compounds of the invention. Although specific starting materials and reagents are depicted in the schemes and discussed below, other starting materials and reagents can be easily substituted to provide a variety of derivatives and / or reaction conditions. In addition, many of the compounds prepared by the methods described below can be further modified considering this disclosure using conventional chemistry well known to those skilled in the art. Preparation Scheme a Scheme a shows a method for the preparation of the isocyanobenzoate compounds of formula (I): Scheme a All the compounds of formula (I) in scheme a were synthesized starting from the intermediate sodium 4- isocyanobenzoate prepared according to literature protocol (ACS Macro Letters (2017), 6(12), 1398-1403) (identified as Intermediate 1). The corresponding amine (1 equiv.), and TEA (1.1 equiv.) were reacted with a 2-chloroacetyl chloride derivative (1.1 equiv.) in dichloromethane at room temperature. After 2 h the reaction was worked up by dilution with dichloromethane and washing with NaHCO3 sol. sat (x1) and brine (x1). After evaporation of the solvent the intermediate 2 (1.2 equiv.) was reacted in a nucleophilic substitution with intermediate 1 (1 equiv.) at 60 °C in DMF. The reaction is heated for 24 h then it is worked up by dilution with EtOAc. The organic phase was washed with water (x2) and brine (x1) and dried over sodium sulphate. After filtration and evaporation of the solvent, the crude was purified by column chromatography using the appropriate petroleum ether / ethyl acetate eluant to obtain the isocyanobenzoates of formula (I). With this strategy, it was possible to explore several substitution patterns on the isocyanobenzoates of formula (I). Preparation Scheme b Scheme b shows a method for the preparation of the isocyanobenzamides compounds of formula (I): Scheme b The corresponding N-Boc protected amino acid (1.5 equiv.) was dissolved in dichloromethane dry. Then, 1 equiv. of the appropriate amine, EDC*HCl (1.5 equiv.), DMAP (0.1 equiv.) were added, and the reaction was stirred at room temperature for 16 h. The reaction was then worked up washing the organic phase with NH4Cl sol sat (x1) and brine (x1). Evaporation of the solvent gave a crude (intermediate 3) which was directly used for the next step. Intermediate 3 (1 equiv.) was dissolved in dichloromethane. The solution was cooled at 0°C and then trifluoroacetic acid (10 equiv.) was added. After 3 h the reaction was worked up by washing with sodium hydroxide 2N (x1) and brine (x1). Evaporation of the solvent gave a crude (intermediate 4) which was directly used for the next step without further purification. Intermediate 4 (1 equiv.) was dissolved in dichloromethane dry. Then, 4- isocyanobenzoic acid (1 equiv.)(intermediate 5), prepared according to literature protocol (ACS Macro Letters (2017), 6(12), 1398-1403), EDC*HCl (1.2 equiv.), DMAP (0.2 equiv.) were added, and the reaction was stirred at room temperature for 16 h. The reaction was then worked up washing the organic phase with water (x1), sodium carbonate sol sat (x1), brine (x1), and dried over sodium sulphate. After filtration and evaporation of the solvent, the crude was purified by column chromatography using the appropriate petroleum ether / ethyl acetate eluant to obtain the isocyanobenzamides of formula (I). With this strategy, it was possible to explore several substitution patterns on the isocyanobenzamides of formula (I). Example 1: Synthesis of 2-(tert-butylamino)-2-oxo-1-phenylethyl 4- isocyanobenzoate (compound 1). Analytical data:1H NMR (400 MHz, CDCl3) δ = 8.18 – 8.12 (m, 2H), 7.57 – 7.51 (m, 2H), 7.49 – 7.40 (m, 5H), 6.18 (s, 1H), 5.80 (s, 1H), 1.36 (s, 9H) ppm.13C NMR (101 MHz, CDCl3) δ = 167.7, 166.9, 163.7, 135.4, 131.1, 130.3 (2C), 129.2, 129.0, 127.6, 126.6, 76.6, 51.8, 28.7 ppm. HRMS (ESI): m / z: calcd for C20H21N2O3+[M+H]+: 337.15524, Found: 337.15439 Example 2: Synthesis of N-benzyl-N-(2-(tert-butylamino)-2- oxoethyl)-4-isocyanobenzamide (compound 2). Analytical data:1H NMR (400 MHz, CDCl3) (referred to the major rotamer) = 7.54 (m, 2H), 7.43 – 7.26 (m, 5H), 7.15 (d, J=7.4, 2H), 5.97 (s, 1H), 4.60 (s, 2H), 3.97 (s, 2H), 1.34 (s, 9H) ppm.13C NMR (101 MHz, CDCl3) δ (referred to the major rotamer) = 170.9, 167.1, 166.0, 136.4, 135.6, 129.0, 128.7, 128.2, 128.0, 127.0, 126.7, 54.0, 51.5, 49.5, 28.7 ppm. HRMS (ESI): m / z: calcd for C21H24N3O2+[M+H]+: 350.18686, Found: 350.18606 Example 3: Synthesis of 2-(tert-butylamino)-2-oxoethyl 4- isocyanobenzoate (compound 3). Analytical data:1H NMR (400 MHz, CDCl3) δ = 8.14 – 8.08 (m, 2H), 7.51 – 7.45 (m, 2H), 5.92 (s, 1H), 4.71 (s, 2H), 1.38 (s, 9H) ppm.13C NMR (101 MHz, CDCl3) δ = 167.6, 165.6, 163.9, 131.1, 130.4 (br s), 130.0, 126.7, 63.9, 51.7, 28.7 ppm. HRMS (ESI): m / z: calcd for C14H16N2NaO3+[M+Na]+: 283.10588, Found: 283.10518 Example 4: Synthesis of 2-(benzylamino)-2-oxoethyl 4- isocyanobenzoate (compound 4). Analytical data:1H NMR (400 MHz, CDCl3) δ = 8.14 – 8.09 (m, 2H), 7.51 – 7.46 (m, 2H), 7.40 – 7.29 (m, 5H), 6.39 (s, 1H), 4.89 (s, 2H), 4.55 (d, J=5.8, 2H) ppm.13C NMR (101 MHz, CDCl3) δ (referred to the major rotamer) = 167.8, 166.5, 163.9, 137.5, 131.1, 130.5 (br s), 129.7, 128.9, 127.8, 127.7, 126.7, 63.8, 43.3 ppm. HRMS (ESI): m / z: calcd for C17H15N2O3+[M+H]+: 295.10829, Found: 295.10808 Example 5: Synthesis of 1-(tert-butylamino)-3-methyl-1-oxobutan-2- yl 4-isocyanobenzoate (compound 5). Analytical data:1H NMR (400 MHz, CDCl3) δ = 8.17 – 8.08 (m, 2H), 7.54 – 7.45 (m, 2H), 5.74 (s, 1H), 5.08 (d, J=4.8 Hz, 1H), 2.48 – 2.34 (m, 1H), 1.35 (s, 9H), 1.05 (d, J=6.8 Hz, 3H), 1.02 (d, J=6.9 Hz, 3H) ppm.13C NMR (101 MHz, CDCl3) δ = 167.8, 167.6, 164.0, 131.0, 130.5, 130.4, 126.7, 79.5, 51.5, 30.7, 28.7, 18.9, 17.2 ppm. HRMS (ESI): m / z: calcd for C17H23N2O3+[M+H]+: 303.17089, Found: 303.17010 Example 6: Synthesis of 2-oxo-2-(phenethylamino)ethyl 4- isocyanobenzoate (compound 6). Analytical data:1H NMR (400 MHz, CDCl3) δ = 8.00 – 7.95 (m, 2H), 7.49 – 7.42 (m, 2H), 7.30 – 7.23 (m, 3H), 7.22 – 7.16 (m, 2H), 6.16 (t, J=6.0 Hz, 1H), 4.77 (s, 2H), 3.63 (q, J=6.5 Hz, 2H), 2.87 (t, J=6.8 Hz, 2H) ppm.13C NMR (101 MHz, CDCl3) δ = 167.9, 166.4, 163.6, 138.4, 131.1, 130.5 (br s), 129.7, 128.8, 128.8, 126.7, 126.7, 63.7, 40.0, 35.4 ppm. HRMS (ESI): m / z: calcd for C18H17N2O3+[M+H]+: 309.12394, Found: 309.12301 Example 7: Synthesis of 1-(benzylamino)-3-methyl-1-oxobutan-2-yl 4-isocyanobenzoate (compound 7). Analytical data:1H NMR (400 MHz, CDCl3) δ (referred to the major rotamer) = 8.18 – 8.07 (m, 2H), 7.55 – 7.43 (m, 2H), 7.39 – 7.22 (m, 5H), 6.27 (t, J=6.0 Hz, 1H), 5.29 (d, J=4.7 Hz, 1H), 4.55 (dd, J=14.9, 5.9 Hz, 1H), 4.47 (dd, J=14.9, 5.8 Hz, 1H), 2.57 – 2.43 (m, 1H), 1.09 (d, J=6.8 Hz, 3H), 1.06 (d, J=6.9 Hz, 3H) ppm.13C NMR (101 MHz, CDCl3) δ (referred to the major rotamer) = 168.8, 167.7, 164.2, 137.8, 131.1, 130.4 (br s), 130.1, 128.8, 127.7 (2C), 126.7, 79.4, 43.3, 30.8, 19.0, 17.3. HRMS (ESI): m / z: calcd for C20H21N2O3+[M+H]+: 337.15524, Found: 337.15447 Example 8: Synthesis of 2-(dodecylamino)-2-oxo-1-phenylethyl 4- isocyanobenzoate (compound 8). Analytical data:1H NMR (400 MHz, CDCl3) δ (referred to the major rotamer) = 8.17 (d, J=8.2 Hz, 2H), 7.60 – 7.37 (m, 7H), 6.28 (s, 1H), 5.95 (t, J=6.1 Hz, 1H), 3.31 (q, J=6.7 Hz, 2H), 1.58 – 1.43 (m, 2H), 1.35 – 1.17 (m, 18H), 0.90 (t, J=6.7 Hz, 3H) ppm.13C NMR (101 MHz, CDCl3) δ = 167.7, 167.65 (br s), 163.7, 135.1, 131.2, 131.2, 130.2, 129.4, 129.0, 127.6, 126.7, 76.5, 39.7, 31.9, 29.6, 29.6, 29.5, 29.5, 29.5, 29.4, 29.2, 26.8, 22.7, 14.1 ppm. HRMS (ESI): m / z: calcd for C28H37N2O3+[M+H]+: 449.28043, Found: 449.27978 Example 9: Synthesis of N-butyl-N-(2-(cyclohexylamino)-2- oxoethyl)-4-isocyanobenzamide (compound 9). Analytical data:1H NMR (400 MHz, CDCl3) δ (referred to the major rotamer) = 7.54 – 7.39 (m, 4H), 6.53 (d, J=8.3 Hz, 1H), 4.08 (s, 2H), 3.82 – 3.75 (m, 1H), 3.28 (t, J=7.6 Hz, 2H), 1.96 – 1.85 (m, 2H), 1.78 – 1.65 (m, 2H), 1.65 – 1.48 (m, 3H), 1.45 – 1.30 (m, 3H), 1.27 – 1.08 (m, 4H), 0.79 (t, J=7.4 Hz, 3H) ppm.13C NMR (101 MHz, CDCl3) δ (referred to the major rotamer) = 170.9, 167.9, 166.0, 136.8, 128.0, 127.5 (br s), 126.7, 51.0, 50.6, 48.2, 32.9 (2C), 30.5, 25.5, 24.6, 19.6, 13.5 ppm. HRMS (ESI): m / z: calcd for C20H28N3O2+[M+H]+: 342.21816, Found: 342.21757 Example 10: Synthesis of N-(2-(cyclohexylamino)-2-oxo-1- phenylethyl)-4-isocyano-N-phenylbenzamide (compound 10). Analytical data:1H NMR (400 MHz, CDCl3) δ = 7.49 – 6.78 (m, 14H), 6.20 (s, 1H), 5.78 (d, J=8.1 Hz, 1H), 3.99 – 3.70 (m, 1H), 2.07 – 1.77 (m, 2H), 1.77 – 1.50 (m, 3H), 1.43 – 1.25 (m, 2H), 1.22 – 0.93 (m, 3H) ppm.13C NMR (101 MHz, CDCl3) δ (referred to the major rotamer) = 169.4, 168.3, 165.3, 140.5, 137.4, 134.4, 130.4, 130.3, 129.6, 128.6, 128.6, 128.6, 127.6, 126.8 (br s), 125.7, 66.5, 48.9, 32.8 (2C), 25.5, 24.7 ppm. HRMS (ESI): m / z: calcd for C28H28N3O2+[M+H]+: 438.21816, Found: 438.21735 Example 11: Synthesis of N-(2-(dodecylamino)-2-oxo-1-phenylethyl)- 4-isocyano-N-phenylbenzamide (compound 11). Analytical data:1H NMR (400 MHz, CDCl3) δ = 7.37 – 7.30 (m, 2H), 7.28 – 7.20 (m, 5H), 7.15 – 7.09 (m, 2H), 7.08 – 6.94 (m, 5H), 6.19 (s, 1H), 5.93 (t, J=5.8 Hz, 1H), 3.40 – 3.21 (m, 2H), 1.47 (p, J=7.0 Hz, 2H), 1.34 – 1.18 (m, 18H), 0.88 (t, J=6.8 Hz, 3H) ppm.13C NMR (101 MHz, CDCl3) δ = 169.4, 169.2, 165.4, 140.6, 137.3, 134.4, 130.4, 130.3, 130.1, 129.7, 128.7, 128.6 (2C), 127.6, 125.7, 66.6, 40.0, 31.9, 29.6, 29.6, 29.5, 29.5, 29.4, 29.3, 29.2, 26.9, 22.7, 14.1 ppm. HRMS (ESI): m / z: calcd for C34H42N3O2+[M+H]+: 524.32771, Found: 524.32765 Example 12: Synthesis of N-butyl-N-(2-(cyclohexylamino)-2-oxo-1- phenylethyl)-4-isocyanobenzamide (compound 12). Analytical data:1H NMR (400 MHz, CDCl3) δ = 7.52 – 7.43 (m, 3H), 7.42 – 7.32 (m, 6H), 6.04 (br s, 1H), 5.80 (br s, 1H), 3.88 – 3.75 (m, 1H), 3.21 (br t, 2H), 1.93 – 1.81 (m, 2H), 1.71 – 1.56 (m, 3H), 1.38 – 1.27 (m, 2H), 1.16 – 0.99 (m, 4H), 0.95 – 0.76 (m, 3H), 0.65 – 0.42 (m, 3H) ppm.13C NMR (101 MHz, CDCl3) δ = 170.9, 168.3, 165.6, 137.9, 135.2, 129.4, 128.9, 128.7, 127.9, 127.1 (br s), 126.6, 63.4 (br s), 48.7, 48.5, 32.7, 31.5, 25.4, 24.8, 19.8, 13.3 ppm HRMS (ESI): m / z: calcd for C26H32N3O2+[M+H]+: 418.24946, Found: 418.24904 Example 13: Synthesis of N-(2-(tert-butylamino)-2-oxo-1- phenylethyl)-4-isocyano-N-(4-methoxyphenyl)benzamide (compound 13). Analytical data:1H NMR (400 MHz, CDCl3) δ = 7.37 – 7.29 (m, 2H), 7.26 – 7.16 (m, 5H), 7.15 – 7.07 (m, 2H), 6.97 – 6.77 (m, 2H), 6.53 – 6.44 (m, 2H), 6.12 (s, 1H), 5.68 (s, 1H), 3.63 (s, 3H), 1.34 (s, 9H) ppm.13C NMR (101 MHz, CDCl3) δ = 169.5, 168.5, 165.2, 158.5, 137.6, 134.6, 132.9, 131.6, 130.3, 129.6, 128.5 (2C), 126.7 (br s), 125.7, 113.5, 66.5, 55.2, 51.7, 28.7 ppm. HRMS (ESI): m / z: calcd for C27H28N3O3+[M+H]+: 442.21308, Found: 442.21266 Example 14: Synthesis of 2-(adamantan-1-ylamino)-2-oxoethyl 4- isocyanobenzoate (compound 14). Analytical data:1H NMR (400 MHz, DMSO-d6) δ = 8.13 – 8.03 (m, 2H), 7.80 – 7.69 (m, 2H), 7.57 (s, 1H), 4.67 (s, 2H), 2.06 – 1.97 (m, 3H), 1.94 (br s, 6H), 1.62 (br s, 6H) ppm.13C NMR (101 MHz, DMSO-d6) δ = 167.2, 165.5, 164.5, 131.3, 131.0, 129.8 (br s), 127.4, 63.7, 51.5, 41.5, 36.4, 29.3 ppm. HRMS (ESI): m / z: calcd for C20H23N2O3+[M+H]+: 339.17089, Found: 339.16980 Example 15: Synthesis of N-(2-(adamantan-1-ylamino)-2-oxo-1- phenylethyl)-4-isocyano-N-phenylbenzamide (compound 15). Analytical data:1H NMR (400 MHz, CDCl3) δ = 7.38 – 7.32 (m, 2H), 7.26 – 7.20 (m, 5H), 7.15 – 7.09 (m, 2H), 7.05 – 6.96 (m, 5H), 6.11 (s, 1H), 5.52 (s, 1H), 2.11 – 2.05 (m, 3H), 2.05 – 1.98 (m, 6H), 1.72 – 1.63 (m, 6H) ppm.13C NMR (101 MHz, CDCl3) δ = 169.3, 168.1, 165.3, 140.5, 137.4, 134.6, 130.4, 130.3, 129.7, 128.5, 127.5 (2C), 126.8 (br s) 125.7 (2C), 67.0, 52.5, 41.4, 36.3, 29.4 ppm. HRMS (ESI): m / z: calcd for C32H32N3O2+[M+H]+: 490.24946, Found: 490.24887 Example 16: Synthesis of 2-(cyclohexylamino)-2-oxoethyl 4- isocyanobenzoate (compound 16). Analytical data:1H NMR (400 MHz, DMSO-d6) δ = 8.14 – 8.05 (m, 2H), 7.98 (d, J=7.9 Hz, 1H), 7.79 – 7.71 (m, 2H), 4.71 (s, 2H), 3.64 – 3.51 (m, 1H), 1.80 – 1.63 (m, 4H), 1.61 – 1.50 (m, 1H), 1.35 – 1.07 (m, 5H) ppm.13C NMR (101 MHz, CDCl3) δ = 167.7, 165.6, 163.9, 131.1, 130.5 (br s), 129.9, 126.7, 63.8, 48.2, 33.0, 25.4, 24.8 ppm. HRMS (ESI): m / z: calcd for C16H19N2O3+[M+H]+: 287.13959, Found: 287.13859 Example 17: Synthesis of 2 N-(2-(cyclohexylamino)-2-oxoethyl)-4- isocyanobenzamide (compound 17). Analytical data:1H NMR (400 MHz, DMSO-d6) δ = 8.85 (t, J=5.9 Hz, 1H), 8.04 – 7.93 (m, 2H), 7.80 (d, J=7.9 Hz, 1H), 7.74 – 7.64 (m, 2H), 3.84 (s, 2H), 3.62 – 3.48 (m, 1H), 1.79 – 1.62 (m, 4H), 1.60 – 1.50 (m, 1H), 1.32 – 1.08 (m, 5H) ppm.13C NMR (101 MHz, DMSO-d6) δ (referred to the major rotamer) = 167.9, 166.1, 165.4, 135.6, 129.3, 128.2 (br s), 126.9, 48.1, 43.0, 32.9, 25.7, 25.0 ppm. HRMS (ESI): calcd for C16H20N3O2+[M+H]+: 286.15556, Found: 286.15496 Example 18: Synthesis of 2-(cycloheptylamino)-2-oxoethyl 4- isocyanobenzoate (compound 18). Analytical data:1H NMR (400 MHz, CDCl3) δ = 8.23 – 8.03 (m, 2H), 7.60 – 7.43 (m, 2H), 5.97 (d, J=8.1 Hz, 1H), 4.80 (s, 2H), 4.12 – 3.95 (m, 1H), 2.06 – 1.86 (m, 2H), 1.70 – 1.41 (m, 10H) ppm.13C NMR (101 MHz, CDCl3) δ = 167.8, 165.2, 163.9, 131.1, 130.5 (br s), 129.9, 126.8, 63.9, 50.4, 35.0, 27.8, 24.0 ppm. HRMS (ESI): m / z: calcd for C17H21N2O3+[M+H]+: 301.15524, Found: 301.15419 Analytical data:1H NMR (400 MHz, CDCl3) δ (referred to the major rotamer) = 8.14 – 8.06 (m, 2H), 7.52 – 7.44 (m, 2H), 7.31 – 7.26 (m, 1H), 7.25 – 7.17 (m, 2H), 7.17 – 7.10 (m, 1H), 6.22 (d, J=8.8 Hz, 1H), 5.35 – 5.27 (m, 1H), 4.89 (s, 2H), 2.82 (q, J=6.0 Hz, 2H), 2.22 – 2.08 (m, 1H), 1.94 – 1.77 (m, 3H) ppm.13C NMR (101 MHz, CDCl3) δ = 167.9, 165.9, 163.9, 137.6, 136.1, 131.1, 130.5, 129.8, 129.3, 128.3, 127.5, 126.7, 126.4, 63.9, 47.5, 30.2, 29.2, 20.2 ppm. HRMS (ESI): m / z: calcd for C20H19N2O3+[M+H]+: 335.13959, Found: 335.13878 Example 20: Synthesis of 2-oxo-2-(phenylamino)ethyl 4- isocyanobenzoate (compound 20). Analytical data:1H NMR (400 MHz, DMSO-d6) δ = 10.19 (s, 1H), 8.19 – 8.08 (m, 2H), 7.81 – 7.71 (m, 2H), 7.59 (d, J=8.0 Hz, 2H), 7.33 (t, J=7.8 Hz, 2H), 7.08 (t, J=7.4 Hz, 1H), 4.96 (s, 2H) ppm.13C NMR (101 MHz, DMSO-d6) δ = 167.4, 165.5, 164.7, 138.9, 131.4, 130.7, 129.9 (br s), 129.3, 127.5, 124.1, 119.9, 64.0 ppm. HRMS (ESI): m / z: calcd for C16H13N2O3+[M+H]+: 281.09264, Found: 281.09189 Example 21: Synthesis of 2-(cyclopentylamino)-2-oxoethyl 4- isocyanobenzoate (compound 21). Analytical data:1H NMR (400 MHz, CDCl3) δ = 8.16 – 8.09 (m, 2H), 7.54 – 7.48 (m, 2H), 5.99 (d, J=6.9 Hz, 1H), 4.80 (s, 2H), 4.28 (h, J=7.1 Hz, 1H), 2.11 – 1.97 (m, 2H), 1.74 – 1.58 (m, 4H), 1.50 – 1.36 (m, 2H) ppm.13C NMR (101 MHz, CDCl3) δ = 167.8, 166.0, 163.9, 131.1, 130.5 (br s), 129.9, 126.8, 63.9, 51.1, 33.1, 23.7 ppm. HRMS (ESI): m / z: calcd for C15H16N2NaO3+[M+Na]+: 295.10588, Found: 295.10498 Example 22: Synthesis of 2-(benzhydrylamino)-2-oxoethyl 4- isocyanobenzoate (compound 22). Analytical data:1H NMR (400 MHz, CDCl3) δ = 8.17 – 8.03 (m, 2H), 7.53 – 7.43 (m, 2H), 7.40 – 7.29 (m, 6H), 7.28 – 7.18 (m, 4H), 6.77 (d, J=8.2 Hz, 1H), 6.33 (d, J=8.1 Hz, 1H), 4.86 (s, 2H) ppm.13C NMR (101 MHz, CDCl3) δ = 167.9, 165.9, 164.1, 140.9, 131.2, 130.6 (br s), 129.9, 128.9, 127.8, 127.4, 126.8, 63.9, 56.9 ppm. HRMS (ESI): m / z: calcd for C23H19N2O3+[M+H]+: 371.13959, Found: 371.13873 Example 23: Synthesis of 2-(butylamino)-2-oxoethyl 4- isocyanobenzoate (compound 23). Analytical data:1H NMR (400 MHz, CDCl3) δ = 8.19 – 8.03 (m, 2H), 7.57 – 7.41 (m, 2H), 6.05 (s, 1H), 4.80 (s, 2H), 3.33 (q, J=6.8 Hz, 2H), 1.52 (p, J=7.3 Hz, 2H), 1.34 (h, J=7.3 Hz, 2H), 0.92 (t, J=7.3 Hz, 3H) ppm.13C NMR (101 MHz, CDCl3) δ = 167.8, 166.4, 163.9, 131.1, 130.6 (br s), 129.9, 126.8, 63.9, 39.1, 31.6, 20.0, 13.7 ppm. HRMS (ESI): m / z: calcd for C14H17N2O3+[M+H]+: 261.12394, Analytical data: 1H NMR (400 MHz, DMSO-d6) δ (referred to the major rotamer) = 9.45 (s, 1H), 8.19 – 8.11 (m, 2H), 7.80 – 7.74 (m, 2H), 7.18 (d, J=7.9 Hz, 1H), 7.07 (t, J=7.7 Hz, 1H), 6.94 (d, J=7.4 Hz, 1H), 4.98 (s, 2H), 2.73 (t, J=5.7 Hz, 2H), 2.59 (d, J=6.3 Hz, 2H), 1.78 – 1.64 (m, 4H) ppm. 13C NMR (101 MHz, CDCl3) δ = 167.9, 165.9, 163.9, 137.6, 136.1, 131.1, 130.5, 129.8, 129.3, 128.3, 127.5, 126.7, 126.4, 63.9, 47.5, 30.2, 29.2, 20.2 ppm. HRMS (ESI): m / z: calcd for C20H19N2O3+[M+H]+: 335.13959, Found: 335.13854 Example 25: Synthesis of 2-(isopropylamino)-2-oxoethyl 4- isocyanobenzoate (compound 25). Analytical data: 1H NMR (400 MHz, CDCl3) δ = 8.23 – 8.03 (m, 2H), 7.59 – 7.44 (m, 2H), 5.89 (d, J=6.5 Hz, 1H), 4.79 (s, 2H), 4.26 – 4.10 (m, 1H), 1.21 (d, J=6.6 Hz, 6H) ppm. 13C NMR (101 MHz, CDCl3) δ = 167.7, 165.6, 163.9, 131.1, 130.5 (br s), 129.9, 126.8, 63.8, 41.5, 22.7 ppm. HRMS (ESI): m / z: calcd for C13H15N2O3+[M+H]+: 247.10829, Found: 247.10912 Example 26: Synthesis of 2-((2,6-dimethylphenyl)amino)-2-oxoethyl 4-isocyanobenzoate (compound 26). Analytical data:1H NMR (400 MHz, DMSO-d6) δ = 9.55 (s, 1H), 8.24 – 8.11 (m, 2H), 7.82 – 7.70 (m, 2H), 7.11 – 7.06 (m, 3H), 4.99 (s, 2H), 2.17 (s, 6H) ppm.13C NMR (101 MHz, DMSO-d6) δ = 167.2, 165.5, 164.7, 135.8, 134.7, 131.5, 130.8, 129.9 (br s), 128.1, 127.4, 127.2, 64.0, 18.5 ppm. HRMS (ESI): m / z: calcd for C18H17N2O3+[M+H]+: 309.12394, Found: 309.12304 Example 27: Synthesis of 2-oxo-2-(o-tolylamino)ethyl 4- isocyanobenzoate (compound 27). Analytical data:1H NMR (400 MHz, DMSO-d6) δ = 9.60 (s, 1H), 8.20 – 8.13 (m, 2H), 7.80 – 7.72 (m, 2H), 7.40 (dd, J=7.8, 1.5 Hz, 1H), 7.24 (dd, J=7.4, 1.8 Hz, 1H), 7.18 (td, J=7.6, 1.8 Hz, 1H), 7.12 (td, J=7.4, 1.4 Hz, 1H), 5.00 (s, 2H), 2.22 (s, 3H) ppm.13C NMR (101 MHz, DMSO-d6) δ = 167.2, 165.7, 164.7, 136.0, 132.6, 131.5, 130.8, 130.8, 129.9 (br s), 127.4, 126.5, 126.1, 125.7, 64.0, 18.2 ppm. HRMS (ESI): m / z: calcd for C17H15N2O3+[M+H]+: 295.10829, Found: 295.10751 Example 28: Synthesis of 2-((4-methoxyphenyl)amino)-2-oxoethyl 4- isocyanobenzoate (compound 28). Analytical data:1H NMR (400 MHz, DMSO-d6) δ = 10.07 (s, 1H), 8.19 – 8.08 (m, 2H), 7.81 – 7.70 (m, 2H), 7.55 – 7.44 (m, 2H), 6.95 – 6.86 (m, 2H), 4.93 (s, 2H), 3.73 (s, 3H) ppm.13C NMR (101 MHz, DMSO-d6) δ = 167.3, 165.0, 164.7, 156.0, 131.9, 131.4, 130.7, 129.9 (br s), 127.4, 121.5, 114.4, 64.0, 55.6 ppm. HRMS (ESI): m / z: calcd for C17H15N2O4+[M+H]+: 311.10321, Found: 311.10235 Example 29: Synthesis of 2-((3,4-dimethoxyphenyl)amino)-2-oxoethyl 4-isocyanobenzoate (compound 29). Analytical data:1H NMR (400 MHz, DMSO-d6) δ = 10.09 (s, 1H), 8.17 – 8.10 (m, 2H), 7.79 – 7.73 (m, 2H), 7.31 (d, J=2.4 Hz, 1H), 7.08 (dd, J=8.6, 2.4 Hz, 1H), 6.90 (d, J=8.7 Hz, 1H), 4.93 (s, 2H), 3.76 – 3.68 (br s, 6H) ppm.13C NMR (101 MHz, DMSO-d6) δ = 167.3, 165.1, 164.7, 149.1, 145.6, 132.4, 131.4, 130.7, 129.9 (br s), 127.5, 112.6, 111.8, 105.0, 64.0, 56.2, 55.8 ppm. HRMS (ESI): m / z: calcd for C18H17N2O5+[M+H]+: 341.11378, Found: 341.11307 Example 30: Synthesis of 2-((2-chlorophenyl)amino)-2-oxoethyl 4- isocyanobenzoate (compound 30). Analytical data:1H NMR (400 MHz, DMSO-d6) δ = 9.84 (s, 1H), 8.20 – 8.10 (m, 2H), 7.82 – 7.70 (m, 3H), 7.52 (dd, J=8.0, 1.5 Hz, 1H), 7.35 (td, J=7.7, 1.5 Hz, 1H), 7.23 (td, J=7.7, 1.7 Hz, 1H), 5.04 (s, 2H) ppm.13C NMR (101 MHz, DMSO-d6) δ = 167.3, 166.1, 164.6, 134.6, 131.5, 130.7, 130.0, 129.9 (br s), 128.0, 127.5, 127.2, 127.1, 126.6, 63.9 ppm. HRMS (ESI): m / z: calcd for C16H12ClN2O3+[M+H]+: 315.05366, Found: 315.05279 Example 31: Synthesis of 2-(benzhydrylamino)-2-oxoethyl 4- isocyanobenzoate (compound 31). Analytical data:1H NMR (400 MHz, DMSO-d6) δ = 10.36 (s, 1H), 8.17 – 8.09 (m, 2H), 7.80 – 7.72 (m, 2H), 7.66 – 7.58 (m, 2H), 7.43 – 7.33 (m, 2H), 4.97 (s, 2H) ppm.13C NMR (101 MHz, DMSO-d6) δ = 167.3, 165.7, 164.7, 137.8, 131.4, 130.6, 129.9 (br s), 129.2, 127.7, 127.5, 121.4, 64.0 ppm. HRMS (ESI): m / z: calcd for C16H12ClN2O3+[M+H]+: 315.05366, Found: 315.05287 Example 32: Synthesis of 2-(naphthalen-1-ylamino)-2-oxoethyl 4- isocyanobenzoate (compound 32). Analytical data:1H NMR (400 MHz, DMSO-d6) δ = 10.24 (s, 1H), 8.27 – 7.98 (m, 4H), 7.88 – 7.74 (m, 3H), 7.64 – 7.42 (m, 4H), 5.15 (s, 2H) ppm.13C NMR (101 MHz, DMSO-d6) δ = 167.3, 166.5, 164.8, 134.2, 133.3, 131.5, 130.8, 129.9 (br s), 128.6, 128.5, 127.4, 126.6, 126.4, 126.2, 126.0, 123.2, 122.5, 64.2 ppm. HRMS (ESI): m / z: calcd for C20H15N2O3+[M+H]+: 331.10829, Found: 331.10739 Example 33: Synthesis of 2-([1,1'-biphenyl]-4-ylamino)-2-oxoethyl 4-isocyanobenzoate (compound 33). Analytical data:1H NMR (400 MHz, DMSO-d6) δ = 10.33 (s, 1H), 8.20 – 8.10 (m, 2H), 7.83 – 7.74 (m, 2H), 7.70 – 7.59 (m, 6H), 7.45 (t, J=7.6 Hz, 2H), 7.34 (t, J=7.4 Hz, 1H), 4.99 (s, 2H) ppm.13C NMR (101 MHz, DMSO-d6) δ = 167.2, 165.6, 164.7, 140.0, 138.3, 135.8, 131.4, 130.7, 129.9 (br s), 129.4 (2C), 127.6, 127.5, 126.7, 120.2, 64.0 ppm. HRMS (ESI): m / z: calcd for C22H17N2O3+[M+H]+: 357.12394, Found: 357.12314 Example 34: Synthesis of 2-((3-ethynylphenyl)amino)-2-oxoethyl 4- isocyanobenzoate (compound 34). Analytical data:1H NMR (400 MHz, DMSO-d6) δ = 10.33 (s, 1H), 8.17 – 8.09 (m, 2H), 7.80 – 7.73 (m, 3H), 7.57 (ddd, J=8.2, 2.2, 1.1 Hz, 1H), 7.35 (t, J=7.9 Hz, 1H), 7.19 (dt, J=7.7, 1.4 Hz, 1H), 4.97 (s, 2H), 4.17 (s, 1H) ppm.13C NMR (101 MHz, DMSO-d6) δ = 167.3, 165.9, 164.7, 139.1, 131.4, 130.6, 129.9 (br s), 129.8, 127.5, 127.3, 122.7, 122.6, 120.4, 83.7, 81.1, 64.0 ppm. HRMS (ESI): m / z: calcd for C18H13N2O3+[M+H]+: 305.09264, Found: 305.09183 Example 35: Synthesis of 2-((3-fluorophenyl)amino)-2-oxoethyl 4- isocyanobenzoate (compound 35). Analytical data:1H NMR (400 MHz, DMSO-d6) δ = 10.45 (s, 1H), 8.19 – 8.07 (m, 2H), 7.82 – 7.72 (m, 2H), 7.57 (m, 1H), 7.42 – 7.27 (m, 2H), 6.96 – 6.86 (m, 1H), 4.98 (s, 2H) ppm.13C NMR (101 MHz, DMSO-d6) δ = 167.3, 165.9, 164.7, 162.6 (d, J=241.6 Hz), 140.6 (d, J=11.0 Hz), 131.4, 131.0 (d, J=9.5 Hz), 130.6, 129.9 (br s), 127.5, 115.5 (d, J=2.8 Hz), 110.6 (d, J=21.1 Hz), 106.6 (d, J=26.4 Hz), 64.0 ppm. HRMS (ESI): m / z: calcd for C16H12FN2O3+[M+H]+: 299.08321, Found: 299.08241 Example 36: Synthesis of 2-((2-methoxyphenyl)amino)-2-oxoethyl 4- isocyanobenzoate (compound 36). Analytical data:1H NMR (400 MHz, DMSO-d6) δ = 9.47 (s, 1H), 8.20 – 8.07 (m, 2H), 7.98 (d, J=7.9 Hz, 1H), 7.83 – 7.72 (m, 2H), 7.17 – 7.02 (m, 2H), 6.92 (t, J=7.4 Hz, 1H), 5.03 (s, 2H), 3.85 (s, 3H) ppm.13C NMR (101 MHz, DMSO-d6) δ = 167.3, 165.6, 164.5, 149.9, 131.4, 130.7, 129.9 (br s), 127.5, 127.1, 125.2, 122.0, 120.8, 111.7, 64.1, 56.2 ppm. HRMS (ESI): m / z: calcd for C17H15N2O4+[M+H]+: 311.10321, Found: 311.10217 Example 37: Synthesis of 2-((3-chlorophenyl)amino)-2-oxoethyl 4- isocyanobenzoate (compound 37). Analytical data:1H NMR (400 MHz, DMSO-d6) δ = 10.42 (s, 1H), 8.16 – 8.10 (m, 2H), 7.80 – 7.73 (m, 3H), 7.48 – 7.44 (m, 1H), 7.36 (t, J=8.1 Hz, 1H), 7.16 – 7.11 (m, 1H), 4.97 (s, 2H) ppm.13C NMR (101 MHz, DMSO-d6) δ = 167.3, 166.0, 164.7, 140.3, 133.6, 131.4, 131.0, 130.6, 129.9 (br s), 127.5, 123.8, 119.3, 118.2, 64.0 ppm. HRMS (ESI): m / z: calcd for C16H12ClN2O3+[M+H]+: 315.05366, Found: 315.05293 Example 38: Synthesis of 2-((2,3-dichlorophenyl)amino)-2-oxoethyl 4-isocyanobenzoate (compound 38). Analytical data:1H NMR (400 MHz, DMSO-d6) δ = 10.01 (s, 1H), 8.17 – 8.12 (m, 2H), 7.80 – 7.75 (m, 2H), 7.72 (dd, J=8.1, 1.5 Hz, 1H), 7.49 (dd, J=8.1, 1.5 Hz, 1H), 7.37 (t, J=8.1 Hz, 1H), 5.05 (s, 2H) ppm.13C NMR (101 MHz, DMSO-d6) δ = 167.3, 166.3, 164.6, 136.6, 132.4, 131.5, 130.6, 129.9 (br s), 128.6, 127.6, 127.5, 125.8, 125.2, 63.9 ppm. HRMS (ESI): m / z: calcd for C16H10Cl2N2NaO3+[M+Na]+: 370.99664, Found: 370.99606 Example 39: Synthesis of 2-((2-ethynylphenyl)amino)-2-oxoethyl 4- isocyanobenzoate (compound 39). Analytical data:1H NMR (400 MHz, DMSO-d6) δ = 9.57 (s, 1H), 8.21 – 8.13 (m, 2H), 7.91 (dd, J=8.3, 1.2 Hz, 1H), 7.83 – 7.75 (m, 2H), 7.53 (dd, J=7.7, 1.6 Hz, 1H), 7.42 (td, J=7.6, 1.7 Hz, 1H), 7.18 (td, J=7.6, 1.2 Hz, 1H), 5.02 (s, 2H), 4.53 (s, 1H) ppm.13C NMR (101 MHz, DMSO-d6) δ = 167.3, 165.9, 164.3, 139.0, 133.2, 131.4, 130.5, 130.1, 130.0 (br s), 127.5, 125.3, 123.1, 114.8, 87.3, 80.0, 64.1 ppm. HRMS (ESI): m / z: calcd for C18H13N2O3+[M+H]+: 305.09264, Found: 305.09178 Example 40: Synthesis of 4-isocyano-N-(2-oxo-2-(phenylamino)ethyl) benzamide (compound 40). Analytical data:1H NMR (400 MHz, DMSO-d6) δ = 10.06 (s, 1H), 9.03 (t, J=5.9 Hz, 1H), 8.05 – 7.98 (m, 2H), 7.75 – 7.68 (m, 2H), 7.64 – 7.57 (m, 2H), 7.31 (t, J=7.9 Hz, 2H), 7.10 – 7.01 (m, 1H), 4.09 (d, J=5.8 Hz, 2H) ppm.13C NMR (101 MHz, DMSO-d6) δ = 168.0, 166.2, 165.7, 139.4, 135.4, 129.4, 129.2, 128.3 (br s), 127.0, 123.7, 119.7, 43.8 ppm. HRMS (ESI): m / z: calcd for C16H14N3O2+[M+H]+: 280.10861, Found: 280.10786 Example 41: Synthesis of 2-((4-ethynylphenyl)amino)-2-oxoethyl 4- isocyanobenzoate (compound 41). Analytical data:1H NMR (400 MHz, DMSO-d6) δ = 10.41 (s, 1H), 8.17 – 8.10 (m, 2H), 7.81 – 7.73 (m, 2H), 7.64 – 7.58 (m, 2H), 7.48 – 7.42 (m, 2H), 4.97 (s, 2H), 4.09 (s, 1H) ppm.13C NMR (101 MHz, DMSO-d6) δ = 167.2, 165.8, 164.7, 139.4, 132.9, 131.4, 130.6, 129.9 (br s), 127.5, 119.6, 117.0, 83.9, 80.5, 64.0 ppm. HRMS (ESI): m / z: calcd for C18H13N2O3+[M+H]+: 305.09264, Found: 305.09189 Example 42: Synthesis of 2-((2-fluorophenyl)amino)-2-oxoethyl 4- isocyanobenzoate (compound 42). Analytical data:1H NMR (400 MHz, DMSO-d6) δ = 10.07 (s, 1H), 8.18 – 8.09 (m, 2H), 7.91 – 7.84 (m, 1H), 7.80 – 7.71 (m, 2H), 7.32 – 7.23 (m, 1H), 7.22 – 7.13 (m, 2H), 5.04 (s, 2H) ppm.13C NMR (101 MHz, DMSO-d6) δ = 167.3, 166.1, 164.6, 154.2 (d, J=245.5 Hz), 131.4, 130.7, 129.9 (br s), 127.5, 126.2 (d, J=7.5 Hz), 125.9 (d, J=11.6 Hz), 124.9 (d, J=3.6 Hz), 124.7 (br s), 116.1 (d, J=19.4 Hz) 63.9 ppm. HRMS (ESI): m / z: calcd for C16H12FN2O3+[M+H]+: 299.08321, Found: 299.08249 Example 43: Synthesis of 2-oxo-2-((2-(trifluoromethyl)phenyl) amino)ethyl 4-isocyanobenzoate (compound 43). Analytical data:1H NMR (400 MHz, DMSO-d6) δ = 9.89 (s, 1H), 8.19 – 8.10 (m, 2H), 7.80 – 7.74 (m, 3H), 7.71 (td, J=7.7, 1.6 Hz, 1H), 7.55 (d, J=8.0 Hz, 1H), 7.52 – 7.46 (m, 1H), 5.00 (s, 2H) ppm.13C NMR 167.5, 166.9, 164.2, 135.0, 133.5, 131,4, 130.6, 130.4, 129.9, 127.6, 127.4, 126.8 (q, J = 3.7 Hz), 125.4 (q, J = 32.1 Hz), 124.0 (q, J = 272,3 Hz), 64.1. HRMS (ESI): m / z: calcd for C17H12F3N2O3+[M+H]+: 349.08001, Found: 349.07918 Evaluation of the antibacterial activity of compounds of formula (I) Minimum Inhibitory Concentrations (MICs) and Minimum Bactericidal Concentrations (MBCs) The MIC of each compound and control antibiotics against S. aureus, MRSA, Mu50 and S. epidermidis strains was determined by the broth microdilution assay as described (Nat. Protoc. 3 (2008) 163–175). After 24 hours of incubation at 37 °C, MBCs were determined as described (J. Med. Chem. 60 (2017) 2425–2438). MICs and MBCs results, reported in Tables 2 and 3, indicate that a series of compounds of formula (I) are characterised by a marked antibacterial activity against the tested strains. Table 2 Table 3 Compound MBC values (μM) for each strain tested S. S. aureus MRSA MRSA S. aureus S. aureus ATCC ATCC ATCC ATCC 700699 epidermidis ATCC 25923 43300 33592 (Mu50) ATCC 35984 6538 16 >8 >4 0.125 0.125 0.5 0.125 14 >4 1 0.06 0.06 0.25 0.06 20 >4 >2 0.25 0.06 0.25 0.125 24 >4 2 0.125 0.06 0.125 0.03 28 >8 4 0.125 0.125 0.125 0.125 29 >8 4 0.125 0.125 0.25 0.125 30 >4 >2 0.125 0.125 0.125 1 31 >4 0.125 0.125 0.125 0.125 0.5 32 >4 2 0.125 0.125 0.125 0.25 33 >8 0.5 0.125 0.125 0.25 0.125 34 >4 >2 0.06 0.06 0.25 0.03 35 >4 0.125 0.06 0.03 0.06 0.03 37 >2 2 >2 2 >2 0.03 38 >2 >2 >2 >2 >2 0.06 41 >2 2 0.03 >2 2 0.03 Time–kill assay The time-kill profile of a selection of compounds on MRSA ATCC 33592 growth was obtained as described (J. Glob. Antimicrob. Resist. 19 (2019) 1–7). Results, shown in Figure 1, indicate that no ≥ 3 log10decrease in MRSA colony forming units per millilitre (CFU / mL) was observed in the presence of compounds 16 and 35 up to 24 h, confirming that compounds of formula (I) are characterised by a bacteriostatic activity. Evaluation of the anti-biofilm activity of compounds of formula (I) The anti-biofilm activity of a selection of compounds of formula (I) against S. aureus ATCC 25923, S. aureus ATCC 700699 (Mu50) and S. epidermidis ATCC 35984 was evaluated as described (Eur J Med Chem. (2023) 246:114950). The results provided in Figure 2 and Table 4 indicate that these compounds are characterised by a marked anti-biofilm activity against the tested strains. Table 4 Strain Compound Percentage (%) of biofilm metabolic activity inhibition for each strain and concentration tested Concentration 2×MIC 4×MIC 8×MIC 16×MIC 32×MIC 64×MIC S. aureus 16 43 58 67 72 87 95 ATCC 25923 20 66 84 94 97 97 98 24 18 35 47 58 79 92 29 84 90 92 94 95 97 30 60 77 86 87 91 94 32 62 76 81 87 94 98 S. aureus 16 99 99 99 99 99 100 Mu50 20 99 99 99 99 99 99 24 99 99 99 99 100 100 29 99 100 100 100 100 100 30 80 89 99 100 100 100 32 99 99 99 99 99 99 S. epidermidis 16 61 83 99 99 99 99 ATCC 35984 20 99 99 99 99 99 99 24 97 98 98 99 99 99 29 99 99 99 99 99 99 30 99 99 99 99 99 99 32 99 99 99 99 99 99 Cytotoxicity of compounds of formula (I) on mammalian cells The most potent antibacterials were assayed to test cytotoxicity (at concentrations range 2-16 μM) using human fibroblasts (MRC5) and human keratinocyte cell line (HaCaT) using the MTT test. After 24 h of treatments, the MTT formazan crystals formed were eluted and measured at 570 nm with a spectrophotometer (VICTOR3V TM, PerkinElmer, Inc., Waltham, MA, USA). As a basal control, we used cells in DMSO to the concentration used in the samples that were tested. Experiments were done in triplicate and repeated three times (n=9). The viability was expressed as % considering 100% the absorbance obtained from the basal control. Statistical evaluation of data was done using Ordinary One-Way Anova, Tukey’s multiple comparison test. Results in Figure 3 showed similar behaviour of HaCaT and MRC5. The compounds tested show a remarkable safety profile. Compounds 14, 24 and 33 show a cell vitality slightly lower than 70% that is the conventional biocompatibility limit used according to ISO parameters (ISO 10993‐5:2009). Evaluation of metabolic stability of compounds of formula (I) The in vitro hydrolytic stability is assessed in Male Wistar Han rat liver microsomes (RLM), (protein concentration: 20 mg / mL, total CYP: 650 pmol / mg protein) and human liver microsomes (HLM), (pooled mixed sex, fifty individual donors, protein concentration: 20 mg / mL, total CYP: 360 pmol / mg protein) which were purchased from Corning B.V. Life Sciences (Amsterdam, The Netherlands). The standard incubation mixture (250 μL final volume) is carried out in a 0.1 M phosphate buffer (pH 7.4), acetonitrile as cosolvent (1% of total volume), and the substrate (50 μM). After pre-equilibration of the mixture, an appropriate volume of microsomal suspension is added to give a final protein concentration of 1.0 mg / mL. The mixture is shaken for 60 min at 37 °C. Control incubations are carried out without the presence of microsomes. Each incubation is stopped by the addition of 250 μL ice-cold acetonitrile, vortexed and centrifuged at 13,000 rpm for 10 min. The supernatants are analyzed by LC-UV on a Thermo Syncronis aQ 5 µm 150 × 4.6 mm as a stationary phase and water (+ 0.2% formic acid) and methanol as eluent pumped in gradient mode. Metabolic stability (Table 5) is expressed as percentage ratio between the substrate peak area after incubation and the substrate peak area dissolved in pure buffer. These data indicate that some compounds (e.g. compound 14) are resistant to metabolism and can be used to treat systemic infections, while others, less resistant to metabolism (e.g. compound 16), are preferred in the treatment of topical infections. Table 5

Claims

CLAIMS 1. A compound of formula (I):wherein A is -NR- or -O-; R is selected from H, C1-8alkyl, substituted or unsubstituted Ar6, substituted or unsubstituted (CH2)lAr6; B is selected from H, C1-8alkyl, C3-6cycloalkyl, Ar1, and (CH2)n-Ar1; C is selected from a substituted or unsubstituted C1-16alkyl, substituted or unsubstituted C3-10cycloalkyl, substituted or unsubstituted Ar2, and substituted or unsubstituted (CH2)m-Ar2, adamantane; D1, D2, D3and D4are independently selected from - H, -CH3,-Cl, and -CF3; n is an integer 1 to 4; m is an integer 1 to 4; l is an integer 1 to 4; Ar1, Ar2and Ar6are independently selected from aryl and heteroaryl; provided that the compound of formula (I) is not.

2. The compound according to claim 1, wherein Ar1, and Ar2independently selected from benzene, naphthalene, thiophene, pyridine, biphenyl, 1,2,3,4- tetrahydronaphthalene.

3. The compound according to claim 1 or claim 2, wherein Ar6is selected from benzene, pyridine, furan, thiophene.

4. The compound according to any one of the preceding claims, wherein, when R is a substituted Ar6, or a substituted (CH2)lAr6, the one or more substituents are independently selected from halogen, -OH, -OCH3, - NO2, methyl, -NH2.

5. The compound according to any one of the preceding claims, wherein R is selected from H, C1-6 alkyl, benzene.

6. The compound according to any one of the preceding claims, wherein B is selected from H, C1-4 alkyl, benzene, (CH2)1-4-benzene.

7. The compound according to any one of the preceding claims, wherein when C is a substituted C1-16 alkyl, a substituted C3-10 cycloalkyl, a substituted Ar2, or a substituted (CH2)m-Ar2, the one or more substituents are selected from halogen, CF3, C1-6 alkyl, C1-6 alkoxy, C2-6 alkynyl, C3-6 cycloalkyl, benzene.

8. The compound according to any one of the preceding claims, wherein C is selected from C1-12 alkyl, C3-7 cycloalkyl, tetrahydronaphtalene, benzene, naphthalene, and adamantane, optionally substitutedwith one or more substituents.

9. The compound according to any one of the preceding claims, wherein the compound of formula (I) is selected from: 2-(tert-butylamino)-2-oxo-1-phenylethyl 4- isocyanobenzoate, N-benzyl-N-(2-(tert-butylamino)-2- oxoethyl)-4-isocyanobenzamide, 2-(tert-butylamino)-2- oxoethyl 4-isocyanobenzoate, 2-(benzylamino)-2-oxoethyl 4-isocyanobenzoate, 1-(tert-butylamino)-3-methyl-1- oxobutan-2-yl 4-isocyanobenzoate, 2-oxo-2- (phenethylamino)ethyl 4-isocyanobenzoate, 1- (benzylamino)-3-methyl-1-oxobutan-2-yl 4- isocyanobenzoate, 2-(dodecylamino)-2-oxo-1-phenylethyl 4-isocyanobenzoate, N-butyl-N-(2-(cyclohexylamino)-2- oxoethyl)-4-isocyanobenzamide, N-(2-(cyclohexylamino)- 2-oxo-1-phenylethyl)-4-isocyano-N-phenylbenzamide, N- (2-(dodecylamino)-2-oxo-1-phenylethyl)-4-isocyano-N- phenylbenzamide, N-butyl-N-(2-(cyclohexylamino)-2-oxo- 1-phenylethyl)-4-isocyanobenzamide, N-(2-(tert- butylamino)-2-oxo-1-phenylethyl)-4-isocyano-N-(4- methoxyphenyl)benzamide, 2-(adamantan-1-ylamino)-2- oxoethyl 4-isocyanobenzoate, N-(2-(adamantan-1- ylamino)-2-oxo-1-phenylethyl)-4-isocyano-N- phenylbenzamide, 2-(cyclohexylamino)-2-oxoethyl 4- isocyanobenzoate, N-(2-(cyclohexylamino)-2-oxoethyl)-4- isocyanobenzamide, 2-(cycloheptylamino)-2-oxoethyl 4- isocyanobenzoate, 2-oxo-2-((1,2,3,4- tetrahydronaphthalen-1-yl)amino)ethyl 4- isocyanobenzoate, 2-oxo-2-(phenylamino)ethyl 4- isocyanobenzoate, 2-(cyclopentylamino)-2-oxoethyl 4- isocyanobenzoate, 2-(benzhydrylamino)-2-oxoethyl 4- isocyanobenzoate, 2-(butylamino)-2-oxoethyl 4- isocyanobenzoate, 2-oxo-2-((5,6,7,8- tetrahydronaphthalen-1-yl)amino)ethyl 4-isocyanobenzoate, 2-(isopropylamino)-2-oxoethyl 4- isocyanobenzoate, 2-((2,6-dimethylphenyl)amino)-2- oxoethyl 4-isocyanobenzoate, 2-oxo-2-(o- tolylamino)ethyl 4-isocyanobenzoate, 2-((4- methoxyphenyl)amino)-2-oxoethyl 4-isocyanobenzoate, 2- ((3,4-dimethoxyphenyl)amino)-2-oxoethyl 4- isocyanobenzoate, 2-((2-chlorophenyl)amino)-2-oxoethyl 4-isocyanobenzoate, 2-((4-chlorophenyl)amino)-2- oxoethyl 4-isocyanobenzoate, 2-(naphthalen-1-ylamino)- 2-oxoethyl 4-isocyanobenzoate, 2-([1,1'-biphenyl]-4- ylamino)-2-oxoethyl 4-isocyanobenzoate, 2-((3- ethynylphenyl)amino)-2-oxoethyl 4-isocyanobenzoate, 2- ((3-fluorophenyl)amino)-2-oxoethyl 4-isocyanobenzoate, 2-((2-methoxyphenyl)amino)-2-oxoethyl 4- isocyanobenzoate, 2-((3-chlorophenyl)amino)-2-oxoethyl 4-isocyanobenzoate, 2-((2,3-dichlorophenyl)amino)-2- oxoethyl 4-isocyanobenzoate, 2-((2- ethynylphenyl)amino)-2-oxoethyl 4-isocyanobenzoate, 4- isocyano-N-(2-oxo-2-(phenylamino)ethyl)benzamide, 2- ((4-ethynylphenyl)amino)-2-oxoethyl 4-isocyanobenzoate, 2-((2-fluorophenyl)amino)-2-oxoethyl 4- isocyanobenzoate, 2-oxo-2-((2- (trifluoromethyl)phenyl)amino)ethyl 4-isocyanobenzoate.

10. A compound of formula (I) for use in the treatment of a pathological condition associated with an infection of a Gram-positive pathogenic bacteriumwherein A, B, C, D1, D2, D3and D4have the meaningset forth in claim 1.

11. A compound of formula (I) for use according to claim 10, wherein the Gram-positive bacterium is selected from Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes, Clostridium botulinum, Clostridium tetani, Listeria monocytogenes, Bacillus anthracis, Staphylococcus epidermidis, Bacillus subtilis, Corynebacterium diphtheriae, Enterococcus faecalis, Nocardia asteroids.

12. A pharmaceutical composition comprising at least one compound of formula (I) and a pharmaceutically acceptable carrierwherein A, B, C, D1, D2, D3and D4have the meaning set forth in claim 1.

13. The pharmaceutical composition according to claim 12 comprising one or more additional therapeutic agents.

14. A pharmaceutical composition comprising at least one compound of formula (I) and a pharmaceutically acceptable carrier for use in the treatment of a pathological condition associated with an infection of a Gram-positive pathogenic bacteriumwherein A, B, C, D1, D2, D3and D4have the meaning set forth in claim 1.

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