MX2008008417A - Boron-containing small molecules - Google Patents

Abstract

This invention relates to compounds useful for treating fungal infections, more specifically topical treatment of onychomycosis and/or cutaneous fungal infections. This invention is directed to compounds that are active against fungi and have properties that allow the compound, when placed in contact with a patient, to reach the particular part of the skin, nail, hair, claw or hoof infected by the fungus. In particular the present compounds have physiochemical properties that facilitate penetration of the nail plate.

Description

SMALL MOLECULES CONTAINING BORO BACKGROUND OF THE INVENTION Infections of the nails and hooves, known as ungular and / or periungular infections, present serious problems in dermatology. These ungular and / or periungular infections can be caused by sources such as fungi, viruses, yeasts, bacteria and parasites. Onychomycosis is an example of these serious ungular and / or periungular infections and is caused by at least one fungus. The current treatment for ungular and / or periungular infections generally falls into three categories: systemic administration of medicine; surgical removal of all or part of the nail or hoof followed by topical treatment of the exposed tissue; or topical application of creams, lotions, gels or conventional solutions, often including the use of bandages to keep these dosage forms in place over the nail or hoof. All these approaches have great disadvantages. The following description is particularly directed to the disadvantages associated with the current treatment of ungular and / or periungular antifungal infections. Long-term systemic (oral) administration of an antifungal agent for the treatment of onychomycosis is commonly required to produce a therapeutic effect on the nail bed. For example, oral treatment with REF: 194288 terbinafine antifungal compound typically requires administration of 200 to 400 mg / day for 12 weeks before any significant therapeutic benefit is achieved. This long-term high-dose systemic therapy can have significant adverse effects. For example, it has been reported that terbinafine has liver toxicity effects and reduces testosterone levels in the blood due to adverse effects on the testicles. Patient cooperation is a problem with these long-term therapies especially those that involve serious adverse effects. In addition, this type of long-term oral therapy is inconvenient in the treatment of a horse or other ruminants afflicted with fungal infections of the hoof. Consequently, the risks associated with parenteral treatments generate significant disincentives against their use and considerable non-cooperation of the patient. Surgical removal of all or part of the nail followed by topical treatment also has severe disadvantages. The pain and discomfort associated with surgery and the unpleasant cosmetic appearance of the nail or bed of the nail represent significant problems, particularly for patients more sensitive to physical appearance. Generally, this type of treatment is not realistic for ruminants such as horses. Topical therapy also has significant problems. Topical dosage forms such as creams, lotions, gels, etc., can not keep the drug in intimate contact with the infected area for therapeutically effective periods of time. Bandages have been used to keep the drug deposits in place in an attempt to increase the absorption of the pharmaceutical agent. However bandages are thick, cumbersome, problematic and generally lead to poor cooperation by the patient. Topical antifungal solutions for hydrophilic and hydrophobic film forming have also been developed. These dosage forms provide improved contact between the drug and the nail. Topical formulations for the treatment of fungal infections have widely attempted to deliver the drug to the target site (an infected nail bed) by diffusion through or across the nail. The nail is more similar to the hair than the stratum corneum with respect to the chemical composition and permeability. Nitrogen is the main component of the nail in relation to the proteinaceous nature of it. The total liquid content of the mature nail is 0.1-1.0%, while the lipids in stratum Corneal is around 10% p / p. The nail is 100-200 times thicker than the stratum corneum and has a very high affinity and ability to bind and retain antifungal drugs. Consequently very little if any drug penetrates through the nail to reach the target site. Due to these reasons, topical therapy for fungal infections has generally been ineffective. Compounds known as penetration or permeation enhancers are well known in the art to produce an improvement in the permeability of the skin or other body membranes to a pharmacologically active agent. The increased permeability allows an improvement in the rate at which the drug passes through the skin and enters the bloodstream. Penetration enhancers have been successful in overcoming the impermeability of pharmaceutical agents through the skin. Nevertheless, the thin stratum corneum layer of the skin, which is approximately 10 to 15 cells thick and is naturally formed by cells migrating to the surface of the skin from the basal layer, has been easier to penetrate than nails. In addition, known penetration enhancers have not proven useful in facilitating the migration of the drug through the nail tissue. Antimicrobial compositions for controlling bacterial and fungal infections comprising a metal chelate of 8-hydroxyquinoline and an alkylbenzenesulfonic acid have been shown to be effective due to the increased ability of the oleophilic group to penetrate lipoid layers of microcells. However, the compounds do not effectively increase the ability to carry the pharmaceutically active antifungal through the cornified layer or stratum corneum of the skin. Patent of E.U.A. No. 4,602,011, West et al., July 22, 1986; patent of E.U.A. No. 4,766,113, West et al., August 23, 1988. Therefore, there is a need in the art for compounds that can penetrate the nail effectively. There is also a need in the art for compounds that can effectively treat ungular and / or periungular infections. These and other needs are solved by the present invention. Aminoacyl-tRNA synthetases (ARS) are a family of essential enzymes that bind amino acids to the terminal 3 'adenosine terminus of tRNA molecules, charged tRNA molecules are then used by the translation machinery to synthesis proteins derived from mRNA. Although there are few exceptions, for example in bacteria and Cram-positive archaea, most organisms have at least one ARS per amino acid. In the case of eukaryotes, they have two ARS, one is located in the cytoplasm while the other ARS is located in the organelles. The ARSs catalyze two reactions, as outlined below, the first reaction adenylates the amino acid with ATP followed by its transfer to the 2 'or 3' hydroxyl of the terminal adenosine of the tRNA. Amino Acid (AA) + ATP- »AA-AMP + PPi; AA-AMP + tRNA? TRNA-AA + AMP The family of 20 ARS is in two different structural classes as determined by its crystalline structure. Class I, which have a double Rossman type 5, include the ARSs for the following amino acids, arginine, cysteine, glutamate, glutamine, isoleucine, leucine, lysine (in arc and some bacteria), valine, methionine, tryptophan and tyrosine. Class II ARSs include the enzymes for the amino acids alanine, asparagine, aspartate, glycine, '"histidine, lysine, phenylalanine, proline, serine and threonine The ARS-mediated reaction is the main point of review for specificity that ensures that the correct amino acid is charged to its cognate tRNA, since some amino acids differ only by a single methylene group, for example valine e Isoleucine, it has been postulated that the specificity of the synthetic reaction alone can not explain the observed in vivo accuracy of tRNA loading. The synthetic active site must be able to exclude amino acids that are not close analogs of the cognate amino acid, but the analogous amino acids have a larger problem. Therefore to increase the specificity, a reading and editing test must occur. So far nine ARSs have been shown to have an editing mechanism that significantly reduces the frequency of poorly loaded tRNA molecules. Enzymes for the following 5 amino acids have been shown to have editing activity: alanine, isoleucine, leucine, methionine, lysine, phenylalanine, proline, threonine and valine. These ARs can hydrolyse the incorrectly adenylated amino acid AA-AMP (pre-transfer editing) or the incorrectly loaded tRNA (post-transfer editing). To date isoleucil, leucil and valil-tRNA synthetases have the best characterized editing mechanisms; an additional structural domain called the connective polypeptide I (CP1) inserted into the synthetic domain has been shown to contain the active editing site. This is located more than 25A away from the synthetic active site, which suggests that both the adenylated amino acid intermediate and the amino acid attached to the 3 'end of the RNA must be moved from the active site in the synthetic domain to the editing site so that the reaction be a reading test. It has been postulated that the 3 'end of the charged RNA is translocated in a manner similar to that of the DNA polymerase reading-proof mechanism. Much less is known about the translocation of the adenylated amino acid. A similar CPl domain is also present in the ARS methionine and cistern enzymes, but it is much smaller than that found in the valine, isoleucine and leucine enzymes. Despite the absence of a direct homologue for the CPl domain in ARS class II, separate editing domains have been found in the enzymes for proline and threonine. Although editing is important to ensure proper loading of tRNA molecules, it is not essential for viability and is not required for the synthesis of charged tRNA molecules. For example, in Escherichia coli, in which 10 amino acids in the edit domain of isoleucyl-tRNA synthetase were loaded into the amine, the resulting mutant was still viable, although it did have many pleiotropic effects, including a remarkable cell growth defect. Despite the significant homologies between human, bacterial and psychotic ARSs, there are a number of compounds that have been developed as anti-infectives. The most notable example of an ARS inhibitor is the commercial antibiotic mupirocin (pseudomonic acid), which is sold under the brand name Bactroban. Mupirocin specifically inhibits bacterial isoleucyl-tRNA synthetases, whereas its activity against the human homologue is more than 1,000 times less active. Mupirocin binds specifically to the synthetic active site and mutants that are resistant to this drug have mutations in the synthetic domain of leucyl-tRNA synthetase. Likewise, reveromycin A inhibits eukaryotic isoleucyl-tRNA synthetases: mutants of resistance to Saccharomyces cerevisiae have mutations in the synthetic domain. So far all attempts to develop better ARS inhibitors than mupirocin, an analog of isoleucine-adenylate, have been based on inhibiting synthetic reactions. Since it has been previously believed that it is not essential for the synthesis of charged tRNA molecules, the editing domain of tRNA synthetases has not been considered a promising target for drug development. Data from mutational analyzes of the ARS editing domains tend to suggest that the inhibition of the editing mechanism leads only to an improvement in the erroneously loaded tRNA molecules and does not lead to cell death. Compounds that are active against, and specific to, the editing domain of the ARNT synthetase would provide access to a new class of antimicrobial therapeutics to increase the arsenal of agents currently in use. Quite surprisingly, the present invention provides these compounds and methods of using them. BRIEF DESCRIPTION OF THE INVENTION In one aspect, the invention provides a structure according to the following formula: wherein R1 and R2 are members independently selected from H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl; R1 and R2, together with the atoms to which they are attached, can optionally be joined to form a 4 to 7 membered ring. Zl is a selected member of R3a and R4a are members independently selected from H, cyano, substituted or unsubstituted alkyl, heteroalkyl substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl. R5 is a member selected from halogen and OR8. R8 is a member selected from H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl. A is a selected member of CR9a and N. D is a selected member of CR10a and N. E is a selected member of CRlla and N. G is a selected member of CR12a and N. R9a, Rlla and R12a are members selected independently from H, OR *, NR * R **, SR *, -S (0) R *, -S (0) 2R *, -S (0) 2NR * R **, nitro, halogen, cyano, substituted alkyl or unsubstituted, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl. Each R * and R ** are members independently selected from H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl. R9a and R10a together with the atoms to which they are attached, optionally join to form a ring. R10a and Rlla, together with the atoms to which they are attached, optionally join to form a ring. Rlla and R12, together with the atoms to which they are attached, optionally join to form a ring. The combination of nitrogens (A + D + E + G) is an integer selected from 0 to 3. BRIEF DESCRIPTION OF THE FIGURES Figures 1A-1C are a table of the data of minimum inhibitory concentration (MIC) of cyclic boronic esters against several mushrooms Figure 2A shows the minimum inhibitory concentration (MIC) for CIO, ciclopirox, terbinafine, fluconazole and itraconazole (comparison drugs) against 19 fungal test strains.

Figure 2B shows the minimum fungicidal concentration (MFC) for CIO, ciclopirox, terbinafine and itraconazole (comparison drugs) against 2 strains of fungal test. Figure 3 shows a comparison of Normalized CIO and Ciclopirox Equivalent in Each Part of Nail Plate Samples After 14 Day Treatment. Figure 4 shows a comparison of CIO and Ciclopirox Equivalent in Cotton Ball Support Bed Samples After 14 Day Treatment. Figure 5 shows the results of a placebo for CIO (50:50 of propylene glycol and ethyl acetate) applied daily for five days. The growth of complete carpet of the organism T. rubrum was observed. Figure 6 shows the results of an aliquot of 40 μL / cm2 of CIO, 10% solution w / v applied once a day for five days. The zones of inhibition (in the order of the cells shown in the figure) of 100%, 67%, 46%, 57%, 38% and 71% were observed for the growth of T. rubrum. The green arrow indicates the measurement of the inhibition zone. Figure 7 shows the results of an aliquot of 40 μL / cm2 of CIO, 10% w / v solution applied daily for five days. The zones of inhibition (in the order of the cells shown in the figure) of 74%, 86%, 100%, 82%, 100% and 84% were observed for the growth of T. rubrum. Figure 8 shows the results of an aliquot of 40 μl / cm2 of 8% ciclopirox in commercial lacquer p / p applied daily for five days. No zone of inhibition was observed; growth of full carpet of T. rubrum. Figure 9 shows the results of an aliquot of 40 μL / cm2 of 5% amorolfine w / v in commercial lacquer applied daily for five days. No zones of inhibition are observed; growth of full carpet of T. rubrum. Figures 10, 10A-10D show the amino acid sequences for leucyl-tRNA synthetase editing domains and tRNA-Leu and tRNA-Ile nucleotide sequences. (Fig. 10A) Amino acid sequences for S. cerivisiae leucyl-tRNA synthetase editing domain in wild type (SEQ ID NO: 1) and over-expressing form (SEQ ID NO: 2); (Fig. 10B) amino acid sequences for leucyl-tRNA synthetase editing domains of indicated species; (Fig. 10C) Genomic nucleotide sequence for tRNA-Leu and tRNA-Ile from S. cerivisiae; in one embodiment of the invention, an aminoacyl tRNA synthetase will bind to the transcribed and methylated products for which these sequences serve as a template; (Fig. 10D) The tRNA-Leu nucleotide sequences of the indicated species. Figures 11A-11F show cyclic boronic ester structures. Figures 12A-12I show different structures for portions of the compounds of the invention.

Figure 13 shows the effect of ATP on the binding of CIO to cdc60. The binding assay was conducted with an initial concentration [CIO] of approximately 72-79uM (pre-equilibrium). Figure 14 shows the binding curve of cdc60 against free [CIO] concentration. Figure 15 shows the data from the PPi exchange reaction experiment to determine the editing speed in the presence and absence of CIO. Figure 16 shows the data of an aminoacylation experiment showing the effect of CIO at different concentrations on the aminoacylation of thetletle. Figure 17 shows the post-transference editing assay carried out in S. cerevisiae at different concentrations of IOC through a range of time points. Figures 18A-18C show the names of exemplary compounds of the invention. Figures 19A-19K show exemplary compounds of the invention. Figures 20A-20H show exemplary compounds of the invention. DETAILED DESCRIPTION OF THE INVENTION I. Definitions and Abbreviations The abbreviations used herein generally have their conventional meaning within the chemical and biological techniques. "Compound of the invention", as used herein, refers to the compounds described herein, to pharmaceutically acceptable salts and prodrugs of these compounds. "Compounds containing boron", as used herein, refers to the compounds of the invention that contain boron as part of their chemical formula. MIC, or minimal inhibitory concentration, is the point at which the compound has more than 50% cell growth, preferably 60% cell growth, preferably 70% cell growth, preferably 80% cell growth, preferably 90% cell growth, in relation to an untreated control. When the substituent groups are specified by their conventional chemical formulas, written from left to right, they also cover the chemically identical substituents, which would turn out to describe the structure from right to left, for example, -CH20- is also designed to describe -OCH2- . The term "poly" as used herein means at least 2. For example, a polyvalent metal ion is a metal ion having a valence of at least 2.

"Portion" refers to the radical of a molecule that is bound to another portion. The symbol, whether used as a link or presented perpendicular to a link, indicates the point at which the presented portion is joined to the rest of the molecule. The term "alkyl", by itself or as part of another substituent, means, unless otherwise indicated, a straight or branched chain or cyclic hydrocarbon radical, or combination thereof, which may be completely saturated, mono - or polyunsaturated and may include di- and multivalent radicals, having a designated carbon atom number (ie, Ci-Cio means one to ten carbons). Examples of saturated hydrocarbon radicals include, but are not limited to, groups such as methyl, ethyl, n-propyl, isopropyl, n-butyl, t-butyl, isobutyl, sec-butyl, cyclohexyl, (cyclohexyl) methyl, cyclopropylmethyl, homologs and isomers of, for example, n-pentyl, n-hexyl, n-heptyl, n-octyl and the like. An unsaturated alkyl group is one having one or more double bonds or triple bonds. Examples of unsaturated alkyl groups include, but are not limited to, vinyl, 2-propenyl, crotyl, 2-isopentenyl, 2- (butadienyl), 2,4-pentadienyl, 3- (1,4-pentadienyl), ethynyl, - and 3-propynyl, 3-butynyl, and homologs and higher isomers. The term "alkyl", unless otherwise indicated, also attempts to include those alkyl derivatives defined in more detail below, such as "heteroalkyl". Alkyl groups that are limited to hydrocarbon groups are called "homoalkyl". The term "alkylene", in itself, or as part of another substituent means a divalent radical derived from an alkane, as exemplified, but not limited by -CH2CH2CH2CH2-, and further includes those groups described below as "heteroalkylene". Typically, an alkyl (or alkylene) group will have from 1 to 24 carbon atoms, with those groups having 10 or fewer carbon atoms being preferred in the present invention. A "lower alkyl" or "lower alkylene" is a shorter chain alkyl or alkylene group, which generally has eight or fewer carbon atoms. The terms "alkoxy", "alkylamino" and "alkylthio" (or thioalkoxy) are used in their conventional sense, and refer to those alkyl groups attached to the rest of the molecule by means of an oxygen atom, an amino group or a sulfur group, respectively. The term "heteroalkyl", itself or in combination with another term, means, unless otherwise indicated, a straight or branched chain cyclic or stable hydrocarbon radical, or combinations thereof, consisting of the indicated number of carbon atoms and at least one heteroatom. In an exemplary embodiment, the heteroatoms may be selected from the group consisting of B, 0, N and S, and wherein the nitrogen and sulfur atoms may optionally be oxidized and the nitrogen heteroatom may optionally be quaternized. The heteroatoms B, 0, N and S can be placed in any internal position of the heteroalkyl group or in the position in which the alkyl group is attached to the rest of the molecule. Examples include, but are not limited to, -CH2-CH2-0-CH3, -CH2-CH2-NH-CH3, -CH2-CH2-N (CH3) -CH3, -CH2-S-CH2-CH3, -CH2 -CH2-S (0) -CH3, -CH2-CH2-S (0) 2-CH3, -CH = CH-0-CH3, -CH2-CH = N-OCH3 and -CH = CH-N (CH3) -CH3. Up to two heteroatoms can be consecutive, such as, for example, -CH2-NH-OCH3. Similarly, the term "heteroalkylene" itself or as part of another substituent means a divalent radical derived from heteroalkyl, as exemplified, but not limited to, -CH2-CH2-S-CH2-CH2- and -CH2- S-CH2-CH2-NH-CH2-. For heteroalkylene groups, heteroatoms may also occupy either or both of the chain terms (eg, alkyleneoxy, alkylenedioxy, alkyleneamino, alkylenediamino, and the like). Moreover, for the alkylene and heteroalkylene linking groups, no orientation of the linking group is implied by the direction in which the formula of the linking group is written. For example, the formula -C (0) 2R'-, represents -C (0) 2R'- and -R'C (0) 2-.

The terms "cycloalkyl" and "heterocycloalkyl", in themselves or in combination with other terms, represent, unless otherwise indicated, cyclic versions of "alkyl" and "heteroalkyl", respectively. In addition, for heterocycloalkyl, a heteroatom can occupy the position in which the heterocycle is attached to the rest of the molecule. Examples of cycloalkyl include, but are not limited to, cyclopentyl, cyclohexyl, 1-cyclohexenyl, 3-cyclohexenyl, cycloheptyl, and the like. Examples of heterocycloalkyl include, but are not limited to, 1- (1,2,5,6-tetrahydropyridyl), 1-piperidinyl, 2-piperidinyl, 3-piperidinyl, 4-morpholinyl, 3-morpholinyl, tetrahydrofuran-2-yl , tetrahydrofuran-3-yl, tetrahydrothien-2-yl, tetrahydrothien-3-yl, 1-piperazinyl, 2-piperazinyl and the like. The terms "halo" or "halogen", in themselves or as part of another substituent, mean, unless otherwise indicated, a fluorine, chlorine, bromine or iodine atom. In addition, terms such as "haloalkyl", are intended to include monohaloalkyl and polyhaloalkyl. For example, the term "C 1 -C 4 haloalkyl" is intended to include, but not be limited to, trifluoromethyl, 2,2,2-trifluoroethyl, 4-chlorobutyl, 3-bromopropyl, and the like. The term "aryl" means, unless otherwise indicated, a polyunsaturated and aromatic substituent which may be single-ring or multi-ring (preferably 1 to 3 rings), which are fused together or covalently linked. The term "heteroaryl" refers to aryl groups (or rings) containing from 1 to 4 heteroatoms. In an exemplary embodiment, the heteroatom is selected from B, N, 0 and S, wherein the nitrogen and sulfur atoms are optionally oxidized, and the nitrogen atoms are optionally quaternized. A heteroaryl group can be attached to the rest of the molecule through a heteroatom. Non-limiting examples of aryl and heteroaryl groups include phenyl, 1-naphthyl, 2-naphthyl, 4-biphenyl, 1-pyrrolyl, 2-pyrrolyl, 3-pyrrolyl, 3-pyrazolyl, 2-imidazolyl, 4-imidazolyl, pyrazinyl, 2-oxazolyl, 4-oxazolyl, 2-phenyl-4-oxazolyl, 5-oxazolyl, 3-isoxazolyl, 4-isoxazolyl, 5-isoxazolyl , 2-thiaxolyl, 4-thiazolyl, 5-thiazolyl, 2-furyl, 3-furyl, 2-thienyl, 3-thienyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrimidyl, 4-pyrimidyl, -benzothiazolyl, purinyl, 2-benzimidazolyl, 5-indolyl, 1-isoquinolyl, 5-isoquinolyl, 2-quinoxalinyl, 5-quinoxalinyl, 3-quinolyl, 6-quinolyl, dioxaborolane, dioxaborinone and dioxaborepane. The substituents for each of the aryl and heteroaryl ring systems indicated above are selected from the group of acceptable substituents described below. For brevity, the term "aryl", when used in combination with other terms (for example aryloxy, arylthioxy, arylalkyl) includes both aryl and heteroaryl rings as defined above. Thus, the term "arylalkyl" is intended to include those radicals in which an aryl group is attached to an alkyl group (eg, benzyl, phenethyl, pyridylmethyl and the like) including those alkyl groups in which a carbon atom (e.g. a methylene group) has been replaced by, for example, an oxygen atom (for example phenoxymethyl, 2-pyridyloxymethyl, 3- (1-naphthyloxy) propyl and the like). Each of the foregoing terms (eg, "alkyl", "heteroarylalkyl", "aryl" and "heteroaryl") attempt to include both substituted and unsubstituted forms of the indicated radical. Preferred substituents for each type of radical are provided below. Substituents for the alkyl and heteroalkyl radicals (including those groups commonly referred to as alkylene, alkenyl, heteroalkylene, heteroalkenyl, alkynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl and heterocycloalkenyl) are generally referred to as "alkyl group substituents" and may be one or more of a variety of groups selected from, but not limited to: -ORA = 0, = NR ', = N-0R', -NR'R ", -SRA -NR '-C (0) NR" R "', NR "C (0) 2R ', -NR-C (NR'R" R "') = NR" ", -NR-C (NR 'R") = NR "', -S (0) R ', - S (0) 2R ', -S (0) 2NR'R ", -NRS02R', -CN and -N02 in a number that varies from zero to (2m '+ l), where m' is the total number of carbon atoms in this radical R ', R ", R"' and R "" each independently preferably refer to hydrogen, substituted or unsubstituted heteroalkyl, substituted or unsubstituted aryl, for example, aryl substituted with 1- 3 halogens, substituted or unsubstituted alkyl, alkoxy or thioalkoxy groups, or arylalkyl groups. When a compound of the invention includes more than one group R, for example, each of the groups R is independently selected like each group R ', R ", R"' and R "" when more than one of these groups is present When R 'and R "are attached to the same nitrogen atom, they may be combined with the nitrogen atom to form a 5, 6 or 7 membered ring, For example, -NR'R" is intended to include, but is not limited to, 1-pyrrolidinyl and 4-morpholinyl. From the foregoing discussion of substituents, one of skill in the art will understand that the term "alkyl" is intended to include groups that include carbon atoms attached to groups that are not hydrogen groups, such as haloalkyl (e.g., -CF3 and -CH2CF3) and acyl (e.g., -C (0) CH3, -C (0) CF3, -C (0) CH2OCH3 and the like). Similar to the substituents described for the alkyl radical, the substituents for the aryl and heteroaryl groups are generically referred to as "aryl group substituents". The substituents are selected from, for example: halogen, -OR ', = 0, = NR', = N-OR ', -NR'R ", -SR', -halogen, -OC (0) R ', - C (0) R ', -C02R', -CONR'R ", -OC (0) NR'R", -NR "C (0) R ', -NR'-C (0) NR" R "' , -NR "C (0) 2R ', -NR-C (NR' R" R "') = NR" ", -NR-C (NR'R") = NR "', -S (0) R ', -S (0) 2NR'R', -NRS02RA -CN and -N02, -R ', -N3, -CH (Ph) 2, C? -C4 fluoroalkoxy and C? -C fluoroalkyl, in a number that varies from zero to the total number of open valencies in the aromatic ring system; and wherein R ', R ", R"' and R "" are preferably independently selected from hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl. When a group of the invention includes more than one group R, for example, each of the groups R is independently selected like each group R ', R ", R"' and R "" when more than one of these groups is present Two of the substituents on adjacent atoms of the aryl or heteroaryl ring can be optionally replaced with a substituent of the formula -TC (O) - (CRR ') qU-, wherein T and U are independently -NR-, -O-, -CRR'- or a single bond, and q is an integer from 0 to 3. Alternatively, two of the substituents on adjacent atoms of the aryl or heteroaryl ring can be optionally replaced with a substituent of the formula -A- (CH2) r - .B-, where A and B are independently -CRR'-, -O-, -NR-, -S-, -S (O) -, -S (0) 2-, -S (0) 2NR '- or a single link, and r is an integer from 1 to 4. One of the individual links of the new ring formed in this way can be optionally replaced with a double link. Alternatively, two of the substituents on adjacent atoms of the aryl or heteroaryl ring can be optionally replaced with a substituent of the formula - (CRR ') SX- (CR "R"') d- / where s and d are independently integers of 0 to 3, and X is -0-, -NR'-, -S-, -S (0) -, -S (0) 2-, or -S (0) 2NR'-. The substituents R, R ', R "and R"' are preferably independently selected from hydrogen or C6-C6 substituted or unsubstituted C6-alkyl. "Ring" as used herein, means a substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl. A ring includes fused ring portions. The number of atoms in a ring is typically defined by the number of members in the ring. For example, a "5 to 7 member ring" means that there are 5 to 7 atoms in the circle arrangement. The ring optionally includes a heteroatom. Thus, the term "5- to 7-membered ring" includes, for example, pyridinyl and piperidinyl. The term "ring" further includes a ring system comprising more than one "ring", wherein each "ring" is independently defined as above. As used herein, the term "heteroatom" includes atoms that are not carbon (C) and hydrogen (H). Examples include oxygen (O), nitrogen (N), sulfur (S), silicon (Si), germanium (Ge), aluminum (Al) and boron (B). The symbol "R" is a general abbreviation representing a substituent group selected from substituted or unsubstituted alkyl groups, substituted or unsubstituted heteroalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl and heterocycloalkyl. substituted or unsubstituted. The term "derivative of" includes its meaning in simple language and also refers to a molecule that is 99%, 98%, 97%, 96%, 95%, 94%, 93%, 92%, 91%, 90% , 89%, 88%, 87%, 86%, 85%, 84%, 83%, 82%, 81%, 80%, 75%, 70%, 65% or 60% homologous to a reference molecule. Molecules mentioned in this definition include RNA or DNA strands, oligonucleotides, polypeptides or proteins of any length and composition. The term "immunological marker" includes oligonucleotides, proteins, antibodies, peptides, polypeptides, enzymes or any other molecule capable of inducing an immune response in suitable animals or cells or of binding specific antibodies. The term "non-cognate" is intended to encompass both the singular and plural forms of the word, ie, the phrase "non-cognate amino acid" comprises one or more amino acids. By "effective" amount of a drug, formulation or permeator is meant a sufficient amount of an active agent to provide the desired local or systemic effect. A "topically effective" amount, "cosmetically effective", "pharmaceutically effective" or "therapeutically effective" refers to the amount of drug that is needed to carry out the desired therapeutic result. "Topically effective" refers to a material that, when applied to the skin, nail, hair, claw or hoof produces a desired pharmacological result either locally at the site of application or systemically as a result of the transdermal passage of an active ingredient in the material . "Cosmetically effective" refers to a material that, when applied to the skin, nail, hair, claw or hoof, produces a desired cosmetic effect locally at the site of application of an active ingredient in the material. The term "pharmaceutically acceptable salts" is intended to include salts of the compounds of the invention which are prepared with relatively non-toxic acids or b, depending on the particular substituents found in the compounds described herein. When the compounds of the present invention contain relatively acidic functionalities, baddition salts can be obtained by contacting the neutral form of these compounds with a sufficient amount of the desired b either concentrated or in a suitable inert solvent. 1 Examples of addition salts with pharmaceutically acceptable bases include sodium, potassium, calcium, ammonium, organic amino or magnesium salt, or a similar salt. When the compounds of the present invention contain relatively basic functionalities, acid addition salts can be obtained by contacting the neutral form of these compounds with a sufficient amount of the desired acid, either concentrated or in a suitable inert solvent. Examples of addition salts with pharmaceutically acceptable acids include those derived from inorganic acids such as hydrochloric, hydrobromic, nitric, carbonic, monohydrogencarbon, phosphoric, monohydrogenphosphoric, dihydrogenphosphoric, sulfuric, monohydrogensulfuric, hydroiodic or phosphorous acids and the like, as well as salts derived from relatively non-toxic organic acids such as acetic, propionic, isobutyric, maleic, masonic, benzoic, succinic, suberic, fumaric, lactic, mandelic, phthalic, benzenesulfonic, p-tolylsulfonic, citric, tartaric, methanesulfonic and the like acids. Also included are salts of amino acids such as arginate and the like, and salts of organic acids such as glucuronic and galacturonic acids and the like (see, for example, Berge et al., "Pharmaceutical Salts", Journal of Pharmaceutical Science 66: 1-19 (1977)). Certain specific compounds of the present invention contain both basic and acidic functionalities which allow the compounds to be converted either into addition salts with bases or acids. The neutral forms of the compounds are preferably regenerated by contacting the salt with a base or acid and isolating the compounds of origin in the conventional manner. The form of origin of the compound differs from the different salt forms in certain physical properties, such as solubility in polar solvents. In addition to the salt forms, the present invention provides compounds that are in the form of a prodrug. Prodrugs of the compounds or complexes described herein easily undergo chemical changes under physiological conditions to provide the compounds of the present invention. In addition, prodrugs can be converted to the compounds of the present invention by chemical or biochemical methods in an ex vivo environment. Certain compounds of the present invention can exist in unsolvated forms as well as in solvated forms, including hydrated forms. In general, solvated forms are equivalent to unsolvated forms and are encompassed within the scope of the present invention. Certain compounds of the present invention can exist in various crystalline or amorphous forms. In general, all physical forms are equivalent for the uses contemplated by the present invention and are intended to be within the scope of the present invention. Certain compounds of the present invention possess asymmetric carbon atoms (optical centers) or double bonds; racemates, diastereomers, geometric isomers or individual isomers are encompassed within the scope of the present invention. The compounds of the present invention may also contain unnatural proportions of atomic isotopes in one or more of the atoms that make up the compounds. For example, the compounds can be radioactively labeled with radioactive isotopes, such as for example tritium (3H), iodine 125 (125I) or carbon 14 (1C). All isotopic variations of the compounds of the present invention, whether radioactive or not, are intended to be encompassed within the scope of the present invention. The term "pharmaceutically acceptable carrier" or "pharmaceutically acceptable carrier" refers to any formulation or carrier medium that provides for the adequate supply of an effective amount of an active agent as defined herein, that does not interfere with the activity's effectiveness. biological agent of the active agent and that is sufficiently non-toxic for the host or patient. Representative carriers include water, oils, both vegetable and mineral, bases for cream, bases for lotions, bases for ointments and the like. These bases include suspending agents, thickeners, penetration enhancers and the like. Its formulation is well known by those trained in the technique of cosmetics and topical pharmaceuticals. Additional information regarding carriers can be found in Remington: The Science and Practice of Pharmacy, 21st ed. , Lippincott, Williams &; Sil ins (2005) which is incorporated herein by way of reference. "Pharmaceutically acceptable topical carrier" and equivalent terms refer to pharmaceutically acceptable carriers, such as those described herein above, suitable for topical application. A liquid carrier or inactive cream capable of suspending or dissolving the active agents, and having the properties of being non-toxic and non-inflammatory when applied to the skin, nail, hair, claw or hoof is an example of a pharmaceutically acceptable topical carrier . This term is specifically intended to encompass carrier materials approved for use in topical cosmetics as well. The term "pharmaceutically acceptable additive" refers to preservatives, antioxidants, fragrances, emulsifiers, colorants and excipients known or used in the field of drug formulation and which do not unduly interfere with the effectiveness of the biological activity of the active agent, and which are sufficiently non-toxic for the host or patient. Additives for topical formulations are well known in the art, and may be added to the topical composition, as long as they are pharmaceutically acceptable and not harmful to epithelial cells or their function. In addition, they should not cause deterioration in the stability of the composition. For example, inert fillers, anti-irritants, thickeners, excipients, fragrances, opacifiers, antioxidants, gelling agents, stabilizers, surfactants, emollients, coloring agents, preservatives, pH regulating agents, other permeation enhancers and other conventional components of supply formulations. topical or transdermal as those known in the art. The terms "improvement", "penetration enhancer" or "improvement of permeation" refer to an improvement in the permeability of the skin, nail, hair, claw or hoof to a drug, in order to increase the speed at which The drug permeates through the skin, nail, hair, claw or hoof. The increased permeation carried out through the use of these enhancers can be observed, for example, by measuring the diffusion rate of the drug through skin, hair, human nails and claws or hooves of animals using a diffusion cell apparatus. A diffusion cell is described by Merritt et al., Diffusion Apparatus for Skin Penetration, J of Controlled Relay, 1 (1984) p. 161-162. The term "permeation enhancer" or "penetration enhancer" refers to an agent or a mixture of agents, which, alone or in combination, act to increase the permeability of the skin, nail, hair or hoof to a drug. The term "excipients" is conventionally known to mean carriers, diluents and / or carriers used to formulate effective drug compositions for the intended use. The term "topical administration" refers to the application of a pharmaceutical agent to the external surface of the skin, nail, hair, claw or hoof, in such a way that the agent crosses the outer surface of the skin, nail, hair, claw or hoof and enter underlying tissues. Topical administration includes the application of the composition to skin, nail, hair, claw or hoof intact, or to a broken, fresh or open wound of skin, nail, hair, claw or hoof. Topical administration of a pharmaceutical agent can result in a limited distribution of the agent to the surrounding skin and tissue or, when the agent is removed from the treatment area by the blood stream, can result in the systemic distribution of the agent. The term "transdermal delivery" refers to the diffusion of an agent through the skin barrier, nail, hair, claw or hoof resulting from topical administration or other application of a composition. The stratum corneum acts as a barrier and few pharmaceutical agents are able to penetrate intact skin. In contrast, the epidermis and dermis are permeable to many solutes and the absorption of drugs therefore occurs more easily through the skin, nail, hair, claw or hoof that is worn or otherwise released from the stratum corneum to expose the epidermis. The transdermal delivery includes injection or other delivery through any portion of the skin, nail, hair, hoof or claw or mucous membrane and absorption or permeation through the remaining portion. Absorption through intact skin, nail, hair, claw or hoof can be increased by placing the active agent in a suitable pharmaceutically acceptable carrier prior to application to the skin, nail, hair, claw or hoof. Passive topical administration may consist of applying the active agent directly to the treatment site in combination with emollients or penetration enhancers. As used herein, transdermal delivery is intended to include delivery by permeation through or beyond the integument, i.e., skin, nail, hair, claw or hoof. The term "microbial infection" refers to any infection of a host tissue by an infectious agent including, but not limited to, viruses, bacteria, mycobacteria, fungi, and parasites (see, for example, Harrison's Principles of Internal Medicine, page 93). -98 (Wilson et al., 12th ed., 1991); Williams et al. J. Of Medicinal Chem. 42: 1481-1485 (1999), each incorporated herein by reference in its entirety. "Biological medium", as used herein, refers to biological media both in vi tro and in vivo. "Biological media" in Vi tro examples include, but are not limited to, cell culture, tissue culture, homogenates, plasma and blood. In vivo applications are generally carried out in mammals, preferably humans. "Inhibit" and "block" are used interchangeably herein to refer to the partial or complete blockage of an editing domain of a tRNA synthetase. "Ventral / intermediate center" as used herein refers to samples of powdered nail drilled from the center of the inner surface (looking at the nail bed) approximately 0.3-0.5 mm deep to the surface. The area is below the dosed site of the nail site but does not include the dosed surface (dorsal nail surface). "Ventral / intermediate center" as used herein refers to the immediate area of the dosed site. "Remaining nail" as used herein refers to the remaining part of the nail that has not been dosed. "Support bed" as used herein refers to the cotton ball placed inside the Teflon chamber of the diffusion cell to provide moisture to the nail plate and also to receive chemicals that penetrate through the nail plate. "Surface washing" as used herein refers to washing with ethanol (or other organic solvents) and soap / water on the surface of the dosed site. "Cell washing" as used herein refers to washing with ethanol (or other organic solvents) and soap / water from the interior of the diffusion cell. A "human nail unit", as defined herein, may be the nail plate, nail bed, bending of the proximal nail, lateral nail bending and combinations thereof. The term "leaving group" means a group or functional atom that can be displaced by another group or functional atom in a substitution reaction, such as a nucleophilic substitution reaction. By way of example, representative leaving groups include triflate, chlorine, bromine and iodine groups; sulphonic ester groups, such as mesylate, tosylate, brosylate, nosylate and the like and acyloxy groups, such as acetoxy, trifluoroacetoxy and the like.

The term "amino protecting group" means a protective group suitable for preventing undesired reactions in an amino nitrogen. Representative amino protecting groups include, but are not limited to, formyl, acyl groups, for example alkanoyl groups, such as acetyl, trichloroacetyl or trifluoroacetyl; alkoxycarbonyl groups, such as tert-butoxycarbonyl groups (Boc); arylmethoxycarbonyl, such as benzyloxycarbonyl (Cbz) and 9-fluorenylmethoxycarbonyl (Fmoc) groups; arylmethyl, such as benzyl (Bn), trityl (Tr) and l, l-di- (4'-methoxyphenyl) methyl groups; silyl, such as trimethylsilyl (TMS) and tert-butyldimethylsilyl (TBS) and the like. The term "hydroxy-protective group" means a protective group suitable for preventing undesirable reactions in a hydroxy group. Representative hydroxy-protecting groups include, but are not limited to, alkyl groups, such as methyl, ethyl, and tert-butyl; acyl groups, for example alkanoyl groups, such as acetyl; arylmethyl groups such as benzyl (Bn), p-methoxybenzyl (PMB), 9-fluorenylmethyl (Fm) and diphenylmethyl (benzhydryl, DPM); silyl groups, such as trimethylsilyl (TMS) and tert-butyldimethylsilyl (TBS); and -similar.

Boron is capable of forming dative bonds with oxygen, sulfur and nitrogen under certain circumstances in this invention. Dative links are usually weaker than covalent bonds. In situations where a boron is covalently bound to at least one oxygen, sulfur or nitrogen, and is at the same time natively bound to an oxygen, sulfur or nitrogen, respectively, the dative bond and the covalent bond between the boron and the two identical heteroatoms can either interconvert or be in the form of a resonance hybrid. There is a potential uncertainty surrounding the exact nature and degree of electron sharing in these situations. The structures provided are not intended to include any and all possible binding scenarios between the boron and the atom to which it is attached. Non-limiting examples of these links are the following: counterion "Salt counterion", as used herein, refers to positively charged ions that are associated with a compound of the invention when the boron is fully negatively charged or partially negatively charged. Examples of salt counter ions include H +, H30 +, ammonium, potassium, calcium, magnesium and sodium. Compounds comprising a boron attached to a carbon and three heteroatoms (such as three oxygens described in this section) may optionally contain a negatively charged boron in complete form or boron partially negatively charged, due to the nature of the dative link between the boron and one of the oxygens. Due to the negative charge, a positively charged counter ion can associate with this compound, thus forming a salt. Examples of positively charged counterions include H +, H30 +, calcium, sodium, ammonium, potassium. The salts of these compounds are implicitly contained in descriptions of these compounds. The present invention also encompasses compounds that are poly- or multivalent species, including, for example, species such as dimers, trimers, tetramers and higher homologs of the compounds of use in the invention or analog homologs thereof. For example, CIO dimers can be formed under the following conditions In another example, C17 dimers can be formed under the following conditions: j YB "* °, The present invention also encompasses compounds that are anhydrides of the cyclic boronic esters are synthesized by subjecting these compounds to dehydrating conditions. Examples of these anhydrides are given below Trimers of the compounds of the invention are also produced. For example, trimers of acyclic boronic esters can be formed as follows: The polymers of the compounds of the invention are also produced through the removal of certain protecting groups in strong acids. For example, trimers of acyclic boronic esters can be formed as follows: Also useful in the present invention are compounds that are poly- or multivalent species including, for example, species such as dimers, trimers, tetramers and higher homologs of the compounds of utility in the invention or relative analogues thereof. The poly and multivalent species can be assembled from a single species or more than one species of the invention. For example, a dimeric construct can be "homodimic" or "heterodimeric". In addition, poly- and multivalent constructs in which a compound of the invention or a reactive analogue thereof, is attached to an oligomeric or polymer framework (eg, polylysine, dextran, hydroxyethyl starch and the like) are within the scope of the present invention. The frame is preferably polyfunctional (ie, it has an arrangement of reactive sites to collect compounds for use in the invention). Moreover, the frame can be derived with a single species of the invention or more than one species of the invention. In addition, the present invention includes the use of compounds within the motif shown in the formulas contained herein, which are functionalized to give compounds having solubility in water that is increased relative to analogous compounds that are not similarly functionalized. Thus, any of the substituents shown herein can be replaced with analogous radicals having increased water solubility. For example, it is within the scope of the invention to replace a hydroxyl group with a diol, or an amine with a quaternary amine, hydroxyamine or similar water-soluble moiety. In a preferred embodiment, the additional water solubility is imparted by substitution at a site nonessential for activity to the editing domain of the compounds shown herein with a portion that increases the water solubility of the parent compounds. Methods for increasing the water solubility of organic compounds are known in the art. These methods include, but are not limited to, functionalization of an organic core with a permanently charged portion, for example, quaternary ammonium, or a group that is charged at a physiologically relevant pH, eg, carboxylic acid, amine. Other methods include attaching groups containing hydroxyl or amine to the organic core, for example alcohols, polyols, polyethers and the like. Representative examples include, but are not limited to, polylysine, polyethylene imine, poly (ethylene glycol) and poly (propylene glycol). Functionalization chemistries and suitable strategies for these compounds are known in the art. See, for example, Duna, R. L., et al., Eds., POLYMERIC DRUGS AND DRUG DELIVERY SISTEMS, ACS Symposium Series vol. 469, American Chemical Society, Washington, D.C. 1991. II. Introduction The present invention provides novel boron compounds and methods for the preparation of these molecules. The invention further provides boron compounds as analogs comprising a functional moiety, such as a drug moiety and methods for using these analogues. YOU. The compounds III. a) Cyclic boronic esters In a first aspect, the present invention provides a compound having a structure according to the formula: where B is boron. Rla is a member selected from a negative charge, a salt counterion, H, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and heteroaryl replaced or not replaced. M is a selected member of oxygen, sulfur and NR2a. R2a is a member selected from H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl., substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl. J is a member selected from (CR3aRa) m and CR5a. R3a, R4a and R5a are members independently selected from H, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl. The index is not an integer selected from 0 to 2.

W is a member selected from C = 0 (carbonyl), (CR6aR7a) m? and CR8a. R6a, R7a and R8a are members independently selected from H, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl. The ml index is an integer selected from 0 and 1. A is a selected member of CR9a and N. D is a selected member of CR10a and N. E is a selected member of CRlla and N.G is a selected member of CR12a and N. R9a, R10a, Rlla and R12a are members independently selected from H, OR *, NR * R **, SR *, S (0) R *, -S (0) 2R *, -S (0) 2NR * R **, -C (0) R *, -C (0) OR *, C (0) NR * R **, nitro, halogen, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted cycloalkyl or unsubstituted, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl. Each R * and R ** are members independently selected from H, nitro, halogen, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl. The combination of nitrogens (A + D + E + G) is an integer selected from 0 to 3. A selected member of R3a, Ra and R5a and a selected member of R6a, R7a and R8a, together with the atoms to which they are united, they are optionally joined to form a ring of 4 to 7 members. R3a and R4a, together with the atoms to which they are attached, optionally join to form a 4 to 7 membered ring. R6a and R7a, together with the atoms to which they are attached, optionally join to form a 4 to 7 membered ring. R6a and R7a, together with the atoms to which they are attached, optionally join to form a 4 to 7 membered ring. R10a and RUa, together with the atoms to which they are attached, optionally join to form a 4- to 7-membered ring. Rlla and R12a, together with the atoms to which they are attached, optionally join to form a 4- to 7-membered ring. In an exemplary embodiment, the compound has a structure according to formula (la): In another exemplary embodiment, each R3q and R4a is a member independently selected from H, cyano, substituted or unsubstituted methyl, substituted or unsubstituted ethyl, trifluoromethyl, substituted or unsubstituted hydroxymethyl, substituted or unsubstituted hydroxyalkyl, substituted or unsubstituted benzyl. , substituted or unsubstituted phenyl, unsubstituted or substituted mercaptomethyl, substituted or unsubstituted mercaptoalkyl, substituted or unsubstituted aminomethyl, substituted or unsubstituted alkylaminomethyl, unsubstituted or substituted dialkylaminomethyl, unsubstituted or substituted arylaminomethyl, unsubstituted or substituted indolyl and amido replaced or not replaced. In another exemplary embodiment, each R3a and R4a is a member independently selected from cyano, substituted or unsubstituted methyl, substituted or unsubstituted ethyl, trifluoromethyl, substituted or unsubstituted hydroxymethyl, substituted or unsubstituted hydroxyalkyl, substituted or unsubstituted benzyl, phenyl substituted or unsubstituted, substituted or unsubstituted mercaptomethyl, substituted or unsubstituted mercaptoalkyl, substituted or unsubstituted aminomethyl, substituted or unsubstituted alkylaminomethyl, substituted or unsubstituted dialkylaminomethyl, substituted or unsubstituted arylaminomethyl, unsubstituted or substituted indolyl and substituted amido or not replaced In another exemplary embodiment, each R3a and R4a is a member selected from H, substituted or unsubstituted methyl, substituted or unsubstituted ethyl, substituted or unsubstituted propyl, substituted or unsubstituted isopropyl, substituted or unsubstituted butyl, substituted t-butyl. or unsubstituted, substituted or unsubstituted phenyl and substituted or unsubstituted benzyl. In another exemplary modality, R3a and R4a is a member selected from methyl, ethyl, propyl, isopropyl, butyl, t-butyl, phenyl and benzyl. In another exemplary embodiment, R3a is H and R4a is a member selected from methyl, ethyl, propyl, isopropyl, butyl, t-butyl, phenyl and benzyl. In another exemplary embodiment, R3a is H and R4a is H. In another exemplary embodiment, each R9a, R10a, Rlla and R12a is a member selected independently from H, OR *, NR * R **, SR *, -S (0 ) R *, -S (0) 2R *, -S (O) 2NR * R **, -C (0) R *, C (0) OR *, -C (0) NR * R **, halogen, cyano, nitro, substituted or unsubstituted methoxy, substituted or unsubstituted methyl, substituted or unsubstituted ethoxy, substituted or unsubstituted ethyl, trifluoromethyl, substituted hydroxymethyl or unsubstituted hydroxyalkyl substituted or unsubstituted, substituted or unsubstituted benzyl, substituted or unsubstituted phenyl, phenyloxy substituted or unsubstituted, phenylmethoxy substituted or unsubstituted, tiofeniloxi substituted or unsubstituted, pyridinyloxy substituted or unsubstituted pyrimidinyloxy substituted or unsubstituted, substituted bencilfurano or unsubstituted, substituted or unsubstituted methylthio, I mercaptomethyl substituted or unsubstituted, mercaptoalkyl substituted or unsubstituted, substituted phenylthio or unsubstituted, substituted tiofeniltio or unsubstituted, substituted phenylmethylthio or unsubstituted, substituted pyridinylthio or substituted, substituted or unsubstituted pyrimidinylthio, substituted or unsubstituted benzylthiuram, substituted phenylsulfonyl or unsubstituted, substituted benzylsulfonyl or unsubstituted, substituted phenylmethyl or unsubstituted tiofenilsulfonilo substituted or unsubstituted pyridinylsulfonyl substituted or unsubstituted, pirimidinilsulfonilo substituted or unsubstituted sulfonamidyl substituted or unsubstituted, substituted phenylsulfinyl or unsubstituted, substituted benzylsulfinyl or unsubstituted substituted fenilmetilsulfinilo or unsubstituted, pirimidilsulfinilo substituted or unsubstituted, pirimidinilsulfinilo substituted or unsubstituted, substituted or unsubstituted amino, alkylamino substituted or unsubstituted, substituted or unsubstituted dialkylamino, unsubstituted trifluoromethylamino substituted or unsubstituted aminomethyl substituted or unsubstituted, alkylaminomethyl substituted or unsubstituted, substituted or unsubstituted dialkylaminomethyl, substituted or unsubstituted arylaminomethyl, substituted or unsubstituted benzylamino, substituted or unsubstituted phenylamino, substituted or unsubstituted thiophenylamino, pyridinylamino substituted or unsubstituted, substituted or unsubstituted pyrimidinylamino, unsubstituted or substituted indolyl, substituted or unsubstituted morpholino, substituted or unsubstituted alkylamido, substituted or unsubstituted arylamido, substituted or unsubstituted ureido, unsubstituted or substituted carbamoyl and substituted piperizinyl or not replaced In an exemplary embodiment, R9a, R10a, Rlla and R12a are selected from the above list of substituents with the exception of -C (0) R *, -C (0) OR *, -C (0) NR * R **. In another exemplary embodiment, R9a, R10a, Rlla and R12a are members independently selected from fluoro, chloro, bromo, nitro, cyano, amino, methyl, hydroxylmethyl, trifluoromethyl, methoxy, trifluoromethoxy, ethyl, diethylcarbamoyl, pyridin-2-yl, pyridin. -3-yl, pyridin-4-yl, pyrimidinyl, piperazino, piperizinyl, piperizinocarbonilo, piperizinilcarbonilo, carboxyl, 1-tetrazolyl, 1-ethoxycarbonylmethoxy, carboxymethoxy, thiophenyl, 3- yl lH-tetrazol-5-(butylcarbonyl) phenylmethoxy, 1-etoxicarbonilmetiloxi-, 1-etoxicarbonilmetilo-, 1-etoxicarbonilo-, carboximetoxi-, thiophen-2-iltio-, thiophen-3-yl, thiophen-3-ylthio, 4-fluorophenylthio, butilcarbonilfenilmetoxi, thiophen-2-yl I butilcarbonilfenilmetilo , butylcarbonylmethyl, 1- (piperidin-1-yl) carbonyl) methyl, 1- (piperidin-1-yl) carbonyl) methoxy, 1- (piperidin-2-yl) carbonyl) methoxy, 1- (piperidin-3-yl) ) carbonyl) methoxy, 1- (4- (pyrimidin-2-yl) piperazin-1-yl) carbonyl) methoxy, 1- (4- (pyrimidin-2-yl) piperazin-1-yl) carbonyl) methyl, - (4- (pyrimidin-2-i l) piperazin-1-yl) carbonyl, 1-4- (pyrimidin-2-yl) piperazin-1-yl, 1- (4- (pyridin-2-yl) piperazin-1-yl) carbonyl), 1- (4- (pyridin-2-yl) piperazin-1-yl) carbonyImethyl, (1- (4- (pyridin-2-yl) piperazin-1-yl) carbonyl) -methoxy), 1- (4- (pyridine -2-yl) piperazin-1-yl, lH-indol-1-yl, morpholino-, morpholinyl, morpholinocarbonyl, orpholinylcarbonyl, phenylureido, phenylcarbamoyl, acetamide, 3- (phenylthio) -lH-indol-1-yl, 3- (2-cyanoethylthio) -lH-indol-1-yl, benzylamino, 5-methoxy-3- (phenylthio) -lH-indol-1-yl, 5-methoxy-3- (2-cyanoethylthio) -lH-indol-1-yl)), 5-chloro-lH-indol-1-yl, 5-chloro-3- (2-cyanoethylthio) -lH-indole -l-yl)), dibenzylamino, benzylamino, 5-chloro-3- (phenylthio) -lH-indol-1-yl), 4- (lH-tetrazol-5-yl) phenoxy, 4- (lH-tetrazole -5-yl) phenyl, 4- (lH-tetrazol-5-yl) phenylthio, 2-cyanophenoxy, 3-cyanophenoxy, 4-cyanophenoxy, 2-cyanophenylthio, 3-cyanophenylthio, 4-cyanofonylthio, 2-chlorophenoxy, 3 -chlorophenoxy, 4-chlorophenoxy, 2-fluorophenoxy, 3-fluorophenoxy, 4-fluorophenoxy, 2-cyanobenzyloxy, 3-cyanobenzyloxy, 4-cyanobenzyloxy, 2-chlorobenzyloxy, 3-chlorobenzyloxy, 4-chlorobenzyloxy, 2-fluorobenzyloxy, 3-fluorobenzyloxy , 4-fluorobenzyloxy, unsubstituted phenyl, unsubstituted benzyl. In an exemplary embodiment, R93 is H and R12 * is H. In an exemplary embodiment, the compound according to formula (I) or formula (la) is a member selected from: In an exary embodiment, the compound has a structure according to one of the formulas I-Io with selections of substituents for R 9a, 10a Rlla and R12a including all possibilities contained in paragraph 106 except for H. In an exary embodiment , the compound has a structure according to one of the formulas Ib-Io with selections of substituents for R9a, R10a, Rlla and R12a including all the possibilities contained in the paragraph 107 except for H. In an exary embodiment, the compound has a formula according to formulas (Ib) - (le) wherein Rla is a selected member of H, a negative charge and a salt counterion and the remaining R group (R9a in Ib, R10a in him, Rlla in Id and R12a in le) is a member selected from fluoro, chloro, bromo, nitro, cyano, amino, methyl, hydroxylmethyl, trifluoromethyl, methoxy, trifluoromethoxy, ethyl, diethylcarbamoyl, pyridin-2-yl, pyridin-3-yl pyridin-4-yl, pyrimidinyl, piperazino, piperizinyl, piperizinocarbonilo, piperizinilcarbonilo, carboxyl, 1-tetrazolyl, 1-ethoxycarbonylmethoxy, carboxymethoxy, thiophenyl, 3- (butylcarbonyl) phenylmethoxy, lH-tetrazol-5-yl, 1-etoxicarbonilmetiloxi- 1-etoxicarbonilmetilo-, 1-etoxicarbonilo-, carboximetoxi-, thiophen-2-yl, thiophen-2-iltio- thiophen-3-yl, thiophen-3-ylthio, 4-fluorophenylthio, butilcarbonilfenilmetoxi, butilcarbonilfenilmetilo, butilcarbonilmetilo, 1- (piperidin-1-yl) carbonyl) methyl, 1- (piperidin-1-yl) carbonyl) methoxy, 1- (piperidin-2-yl) carbonyl) methoxy, 1- (piperidin-3-yl) carbonyl) methoxy, l- (4- (Pyrimidin-2-yl) piperazin-1-yl) carbonyl) methoxy, 1- (4- (pyrimidin-2-yl) piperazin-1-yl) carbonyl) methyl, 1- (4- ( pyrimidin-2-yl) piperazin-1-yl) carbonyl, 1-4- (pyro imidin-2-yl) piperazin-1-yl, 1- (4- (pyridin-2-yl) piperazin-1-yl) carbonyl), 1- (4- (pyridin-2-yl) piperazin-1-yl) ) carbonylmethyl, (1- (4- (pyridin-2-yl) piperazin-1-yl) carbonyl) -methoxy), 1- (4- (pyridin-2-yl) piperazin-1-yl, 1H-indole- 1-yl, morpholino-, morpholinyl, morpholinocarbonyl, morpholinylcarbonyl, phenylureido, phenylcarbamoyl, acetamido, 3- (phenylthio) -lh yl-indol-1-, 3- yl -lh-indol-1-(2-cyanoethylthio) benzylamino , 5-methoxy-3- (phenylthio) -lH-indol-1-yl, 5-methoxy-3- (2-cyanoethylthio) -lH-indol-1-yl), 5-chloro-lH-indol-1 -yl, 5-chloro-3- (2-cyanoethylthio) -lH-indol-1-yl)), dibenzylamino, benzylamino, 5-chloro-3- (phenylthio) -lH-indol-1-yl)), - (lH-tetrazol-5-yl) phenoxy, 4- (lH-tetrazol-5-yl) phenyl, 4- (lH-tetrazol-5-yl) phenylthio, 2-cyanophenoxy, 3-cyanophenoxy, 4-cyanophenoxy, 2-cyanophenylthio, 3-cyanophenylthio, 4-cyanophenylthio, 2-chlorophenoxy, 3-chlorophenoxy, 4-chlorophenoxy, 2-fluorophenoxy, 3-fluorophenoxy, 4-fluorophenoxy, 2-cyanobenzyloxy, 3-cyanobenzyloxy, 4-cyanobenzyloxy, 2- chlorobenzyloxy, 3-chlorobenzyloxy, 4-chlorobenzyloxy, 2-fluorobenzyloxy, 3-fluorobenzyloxy, 4-fluorobenzyloxy. In an exary embodiment, the compound has a formula according to the formulas (If) - (Ik) wherein Rla is a selected member of H, a negative charge and a salt counterion and each of the two remaining R groups ( R9a and R10a in If, R9a and Rlla in Ig, R9a and R12a in Ih, R10a and RUa in Ii, Ri0a and Ri2a in? ^ ^ R? Ia and Ri2a in Ik) is a selected element. independently of fluoro, chloro, bromo, nitro, cyano, amino, methyl, hydroxylmethyl, trifluoromethyl, methoxy, trifluoromethoxy, ethyl, diethylcarbamoyl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, pyrimidinyl, piperazino, piperizinyl, piperizinocarbonilo, piperizinilcarbonilo, carboxyl, 1-tetrazolyl, 1-ethoxycarbonylmethoxy, carboxymethoxy, thiophenyl, 3- yl 1H-tetrazol-5-(butylcarbonyl) phenylmethoxy, 1-etoxicarbonilmetiloxi-, 1-etoxicarbonilmetilo-, 1-etoxicarbonilo-, carboximetoxi-, thiophen-2-yl, thiophen-2-iltio-, thiophen-3-yl, thiophen-3-ylthio, 4-fluorophenylthio, butilcarbonilfenilmetoxi, butilcarbonilfenilmetilo, butilcarbonilmetilo, 1- (piperidin-1-yl) carbonyl) methyl , 1- (piperidin-1-yl) carbonyl) methoxy, 1- (piperidin-2-yl) carbonyl) methoxy, 1- (piperidin-3-yl) carbonyl) methoxy, 1- (4- (pyrimidine-2- il) piperazin-1-yl) carbonyl) methoxy, 1- (4- (pyrimidin-2-yl) piperazin-1-yl) carbonyl) methyl, 1- (4- (pyrimidin-2-yl) piperazin-1-yl) carbonyl, 1-4- (pyrimidin- 2-yl) piperazin-1-yl, 1- (4- (pyridin-2-yl) piperazin-1-yl) carbonyl), 1- (4- (pyridin-2-yl) piperazin-1-yl) carbonylmethyl , (1- (4- (pyridin-2-yl) piperazin-1-yl) carbonyl) -methoxy), 1- (4- (pyridin-2-yl) piperazin-1-yl, lH-indol-1- ilo, morpholino-, morpholinyl, morpholinocarbonyl, morpholinylcarbonyl, phenylureido, phenylcarbamoyl, acetamide, 3- (phenylthio) -lH-indol-1-yl, 3- (2-cyanoethylthio) -lH-indol-1-yl, benzylamino, -methoxy-3- (phenylthio) -lH-indol-1-yl, 5-methoxy-3- (2-cyanoethylthio) -1H-indol-1-yl), 5-chloro-lH-indol-1-yl , 5-chloro-3- (2-cyanoethylthio) -lH-indol-1-yl)), dibenzylamino, benzylamino, 5-chloro-3- (phenylthio) -lH-indol-1-yl), 4- ( lH-tetrazol-5-yl) phenoxy, 4- (lH-tetrazol-5-yl) phenyl, 4- (lH-tetrazol-5-yl) phenylthio, 2-cyanophenoxy, 3-cyanophenoxy, 4-cyanophenoxy, 2- cyanophenylthio, 3-cyanophenylthio, 4-cyanophenylthio, 2-chlorophenoxy, 3-chlorophenoxy i, 4-chlorophenoxy, 2-fluorophenoxy, 3-fluorophenoxy, 4-fluorophenoxy, 2-cyanobenzyloxy, 3-cyanobenzyloxy, 4-cyanobenzyloxy, 2-chlorobenzyloxy, 3-chlorobenzyloxy, 4-chlorobenzyloxy, 2-fluorobenzyloxy, 3-fluorobenzyloxy, 4-fluorobenzyloxy. In an exemplary embodiment, the compound has a formula according to formulas (II) - (lo) wherein Rla is a selected member of H, a negative charge and a salt counterion and each of the three remaining R groups (R9a, R10a, Rlla in (II), R9a, R10a, R12a in (Im), R9a, Rlla, R12a in (In), R10a, Rlla, R12a in (10)) is a member independently selected from fluoro, chloro, bromo, nitro, cyano, amino, methyl, hydroxylmethyl, trifluoromethyl, methoxy, trifluoromethoxy, ethyl, diethylcarbamoyl, pyridin-2- ilo, pyridin-3-yl, pyridin-4-yl, pyrimidinyl, piperazino, piperizinyl, piperizinocarbonyl, piperizinylcarbonyl, carboxyl, 1-tetrazolyl, 1-ethoxycarbonylmethoxy, carboxymethoxy, thiophenyl, 3- (butylcarbonyl) phenylmethoxy, 1H-tetrazole-5 -yl, 1-ethoxycarbonylmethyloxy-, 1-ethoxycarbonylmethyl-, 1-ethoxycarbonyl-, carboxymethoxy-, thiophen-2-yl, thiophen-2-ylthio-, thiophen-3-yl, thiophen-3-ylthio, 4-fluorophenylthio, butylcarbonylphenylmethoxy, butylcarbonylphenylmethyl, butylcarbonylmethyl, 1- (piperidin-1-yl) carbonyl) methyl, 1- (piperidin-1-yl) carbonyl) methoxy, 1- (piperidin-2-yl) carbonyl) methoxy, 1- (piperidine) 3-yl) carbonyl) methoxy, 1- (4- (pyrimidin-2-yl) piperazin-1-yl) carbonyl) methoxy, 1- (4- (pyrimidin-2-yl) piperazin-1-yl) carbonyl) methyl, 1- (4- (pyrimidin-2-yl) piperazi nl-yl) carbonyl, 1-4- (pyrimidin-2-yl) piperazin-1-yl, 1- (4- (pyridin-2-yl) piperazin-1-yl) carbonyl), 1- (4- ( pyridin-2-yl) piperazin-1-yl) carbonylmethyl, (1- (4- (pyridin-2-yl) piperazin-1-yl) carbonyl) -methoxy), 1- (4- (pyridin-2-yl) ) piperazin-1-yl, lH-indol-1-yl, morpholino-, morpholinyl, morpholinocarbonyl, morpholinylcarbonyl, phenylureido, phenylcarbamoyl, acetamide, 3- (phenylthio) -lH-indol-1-yl, 3- (2-cyanoethylthio) ) -lH-indol-1-yl, benzylamino, 5-methoxy-3- (phenylthio) -lH-indol-1-yl, 5-methoxy-3- (2-cyanoethylthio) -1H-indol-1-yl) ), 5-chloro-lH-indol-l-yl, 5-chloro-3- (2-cyanoethylthio) -lH-indol-1-yl), dibenzylamino, benzylamino, 5-chloro-3- (phenylthio) - lH-indol-1-yl)), 4- (lH-tetrazol-5-yl) phenoxy, 4- (lH-tetrazol-5-yl) phenyl, 4- (lH-tetrazol-5-yl) phenylthio, 2 -cyanophenoxy, 3-cyanophenoxy, 4-cyano-phenoxy, 2-cyanophenylthio, 3-cyanophenylthio, 4-cyanophenylthio, 2-chlorophenoxy, 3-chlorophenoxy, 4-chlorophenoxy, 2-fluorophenoxy, 3-fluorophenoxy, 4-fluorophenoxy, 2-cyanobenzyloxy , 3-cyano benzyloxy, 4-cyanobenzyloxy, 2-chlorobenzyloxy, 3-chlorobenzyloxy, 4-chlorobenzyloxy, 2-fluorobenzyloxy, 3-fluorobenzyloxy, 4-fluorobenzyloxy. In an exemplary embodiment, there is a condition that the compound can not be a selected member of Figure 11. In another exemplary embodiment, there is a condition that the compound can not be a selected member of C1-C40. In another exemplary embodiment, there is a condition that the compound can not have the structure according to the formula (Ix): wherein R7b is a member selected from H, methyl, ethyl and phenyl. R10b is a member selected from H, OH, NH2, SH, halogen, substituted or unsubstituted phenoxy, unsubstituted or substituted phenylalkyloxy, substituted or unsubstituted phenylthio, and unsubstituted or substituted phenylalkylthio. Rllb is a member selected from H, OH, NH2, SH, methyl, substituted or unsubstituted phenoxy, unsubstituted or substituted phenylalkyl, unsubstituted or substituted phenylthio, and unsubstituted or substituted phenylalkylthio. In another exemplary embodiment, there is a condition that the compound can not have a structure according to formula (Ix) wherein Rlb is a member selected from a negative charge, H and a salt counterion. In another exemplary embodiment, there is a condition that the compound can not have a structure according to formula (ix) wherein R10b and Rllb are H. In another exemplary embodiment, there is a condition in which the compound can not have a structure according to 5 formula (ix) wherein one member selected from R10b and Rllb is H and the other member selected from R10b and Rllb is a member selected from halo, methyl, cyano, methoxy, hydroxymethyl and p-cyanophenyloxy. In another exemplary embodiment, there is a condition that the compound can not have a structure according to formula (ix) wherein R10b and Rllb are members independently selected from fluoro, chloro, methyl, cyano, methoxy, hydroxymethyl and p-cyanophenyl . In another exemplary embodiment, there is a condition in which the compound can not have a structure according to formula (ix) wherein Rlb is a member selected from a negative charge, H and a salt counterion; R7b is H; R10b is F and Rllb is H. In another exemplary embodiment, there exists a condition in which the compound can not have a structure according to formula (Ix) wherein Rllb and R12b, together with the atoms to which they are attached, join to form a phenyl group. In another exemplary embodiment, there is a condition in which the compound can not have a structure according to formula (Ix) wherein Rlb is a member selected from a negative charge, H and a salt counterion; R7b is H; R10b is 4-cyanophenoxy; and Rllb is H. In another exemplary embodiment, there is a condition in which the compound can not have a structure according to the formula (Iy) wherein R 10b is a member selected from H, halogen, CN and C?-substituted or unsubstituted alkyl. In another exemplary embodiment, there is a condition that a structure does not have the compound that is a member selected from formulas (I) to (lo) at least one member selected from R3a, R4a, R5a, R6a, R7a, R8a, R9a , R10a, Rlla and R12a is nitro, cyano or halogen. In another exemplary embodiment, there is a condition that when M is oxygen, W is a member selected from (CR3aR4a) m, where ni is 0, J is a member selected from (CR6aR7a) m ?, where ml is 1, A is CR9a, D is CR10a, E is CRlla, G is CR12a, R9a is non-halogen, methyl, ethyl or optionally linked with R10a to form a phenyl ring; R10a is not unsubstituted phenoxy, C (CH3) 3, halogen, CF3, methoxy, ethoxy or optionally linked with R9a to form a phenyl ring; Rlla is not halogen or is optionally linked with R10a to form a phenyl ring and R12a is not halogen. In another exemplary embodiment, there is a condition that when M is oxygen, W is a member selected from (CR3aR4a) m, where ni is O, J is a member selected from (CR ^ R73) ^, where ml is 1 , A is CR9a, D is CR10a, E is CRlla, Gl is CR12a, then neither Rfe nor R7a are halofenyl. In another exemplary embodiment, there is a condition that when M is oxygen, W is a member selected from (CR3 ^ 3)!], Where ni is 0, J is a member selected from (CR6 ^ 73) ^, wherein ml is 1, A is CR93, D is CR10a, E is CRlla, G is CR12a and R9a, R10a and Rlla are H, then R63, R7a and R1 a are not H. In another exemplary embodiment, there is a condition of that when M is oxygen where ni is 1, J is a member selected from (CR ^ R 3) ^, where ml is 0, A is CR9a, D is CR10a, E is CRlla, G is CR123, R9a is H , R10a is H, Rlla is H, R63 is H, R7a is H, R123 is H, then W is not C = 0 (carbonyl). In another exemplary embodiment, there is a condition that when M is oxygen, W is CR53, J is CR83, A is CR93, D is CR10a, E is CRlla, G is CR123, R63, R7a, R9a, R10a, Rlla and R12a are H, then R53 and R83, together with the atoms to which they are attached, do not form a phenyl ring. In an exemplary embodiment, the compound of the invention has a structure that is a member selected from: where q is a number between 0 and 1. R9 is halogen. Ra, Rb, Rc, Rd and Re are members independently selected from a selected member of H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl. In an exemplary embodiment, there is a condition that the compound is not a member selected from In an exemplary embodiment, the compound has a structure that is a member selected from: (? aj) and (íak).

In an exemplary embodiment, Ra, Rd and Re are each members selected independently of: In an exemplary embodiment, Rb and Rc are members independently selected from H, methyl, In another exemplary embodiment, Rb is H and Rc is a member selected from H, In another exemplary embodiment, Rb and Rc are, together with the nitrogen to which they are attached, optionally attached to form a member selected from In another exemplary embodiment, Ra is a member selected from Eto s, H In an exemplary mode, Rd is a selected member of In an exemplary mode, Re is a selected member of In an exemplary embodiment, the compound is a member selected from In an exemplary embodiment, the compound has a structure that is described in Figures 19A-19K. In an exemplary embodiment, the compound has a structure that is described in Figures 20A-20H. In an exemplary embodiment, the compound has a structure according to a member selected from formulas I (b), I (c), I (d) and I (e) wherein the remaining group R (R9a for I (b) ), R10a for I (c), RUa for I (d) and R12a for I (e)) is carboxymethoxy. In an exemplary embodiment, the compound has a structure that is a member selected from the formulas (If) - (Ik), wherein either R9a or R10a for the formula (If), either R9a or Rlla for the formula (Ig) ), either R9a or R12a for the formula (Ih), either R10a or Rlla for the formula (Ii), either R10a or R12a for the formula (Ij), either Rlla or R12a for the formula (Ik) is halogen, and the other substituent in the pair (for example if R9a is F in the formula (If), then R10a is selected from the following list of substituents), it is a member selected from NH2, N (CH3) H and N (CH3) 2. In another exemplary embodiment, the compound has a structure that is a member selected from: wherein R * and R ** are members selected from: H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl replaced. In an exemplary embodiment, the compound is a member selected from where Rla is a selected member of a negative charge, H and a counterion of salt. In another exemplary embodiment, the compound has a structure that is a member selected from: (Iak), where q is 1 and R9 is a selected member of fluoro, chloro and bromo. In another exemplary embodiment, the compounds and embodiments described above in formulas (I) - (lo) can form a hydrate with water, a solvate with an alcohol (eg, methanol, ethanol, propanol); an adduct with an amino compound (for example, ammonia, methylamine, ethylamine); an adduct with an acid (for example, formic acid, acetic acid); complexes with ethanolamine, quinoline, amino acids and the like. In another exemplary embodiment, the compound has a structure according to formula (Ip): wherein Rx2 is a member selected from substituted or unsubstituted C1-C5 alkyl and substituted or unsubstituted C1-C5 heteroalkyl. R 2 and R x 2 are members independently selected from H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl. In another exemplary embodiment, the compound has a structure according to formula (Iq): where B is boron. Rx2 is a member selected from substituted or unsubstituted C1-C5 alkyl and substituted or unsubstituted C1-C5 heteroalkyl. > and 2 R, 2xx are members independently selected from H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl, In other exemplary embodiment, at least one member selected from R3a, Ra, R5a, R6a, R7a, R8a, R9a, R10a, Rlla and R12a is a member selected from nitro, cyano and halogen. In another exemplary embodiment, the compound has a structure that is a member selected from the following formulas: In another exemplary embodiment, the compound has a formula according to formulas (Ib) - (le) wherein at least one member selected from R3a, R4a, R5a, R6a, R7a, R8a, R9a, R, 110a Rlla and R12a is a member selected from nitro, cyano, fluoro, chloro, bromo and cyanophenoxy. In another exemplary embodiment, the compound is a member selected from In another exemplary embodiment, the compound is a member selected from In another exemplary embodiment, there is a condition that the compound can not have a structure according to the formula (Iaa): wherein R6, R913, R10b, Rllh and R123 have the same lists of substituents as those described for formulas (Ix) and (Iy) above. In another exemplary embodiment, the invention provides poly- or multivalent species of the compounds of the invention. In an exemplary embodiment, the invention provides a dimer of the compounds described herein. In an exemplary embodiment, the invention provides a dimer of the compounds described herein. In an exemplary embodiment, the invention provides a dimer of a compound that is a member selected from C1-C96. In an exemplary modality the dimer is a selected member of In an exemplary embodiment, the invention provides an anhydride of the cappings described herein. In an exemplary embodiment, the invention provides an anhydride of the compounds described herein. In an exemplary embodiment, the invention provides an anhydride of a co-compound that is a member selected from C1-C96. in an exemplary embodiment the anhydride is a member selected from and In an exemplary embodiment, the invention provides a trimer of the compounds described herein. In an exemplary embodiment, the invention provides a trimer of the compounds described herein. In an exemplary embodiment, the invention provides a trimer of a compound that is a member selected from C1-C96. In an ejepplar modality the trimer is a selected member Pyridinyloxaboroles In an exemplary embodiment, the compound has a structure that is a member selected from the formulas (lia), (Ilb), (lie) and (lid) Oxaborinos In an exemplary embodiment, the compound has a structure according to formula (III): I. b. ) Cyclic Borinic Esters In one aspect, the invention provides compounds useful in methods having a structure according to formula VII: wherein they are described anywhere in the present. In an exemplary embodiment of formula (VII), R1 is unsubstituted or substituted (C? -C) alkyl. In an exemplary embodiment of the formula (VII), R1 is substituted or unsubstituted alkyloxy. In an exemplary embodiment of the formula (VII), R1 is substituted or unsubstituted cycloalkyl (C3-C7). In an exemplary embodiment of the formula (VII), R 1 is substituted or unsubstituted alkenyl. In an additional exemplary embodiment thereof, the substituted alkenyl has the structure wherein R23, R24 and R25 are each members independently selected from H, haloalkyl, aralkyl, substituted aralkyl, (CH2) rOH (wherein r = 1 to 3), CH2NR26R27 (wherein R26 and R27 are independently selected from hydrogen and alkyl), C02H, at < juyl of C02, CONH2, S-alkyl, S-aryl, alkyl of S02, S03H, SCF3, CN, halogen, CF3, N02, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted heterocycloalkyl or unsubstituted, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl. In another exemplary embodiment of the formula (VII), R1 is a substituted or unsubstituted alkynyl. In an exemplary further embodiment thereof, the substituted alkynyl has the structure wherein R2 In an exemplary embodiment of the formula (VII), R1 is substituted or unsubstituted aryl. In a further embodiment thereof the substituted aryl has the structure wherein R28, R29, R30, R31 and R32 are each members independently selected from H, aralkyl, substituted aralkyl, (CH2) sOH (where s = 1 to 3), C02H, C02 alkyl, CONH2, CONHalkyl, CON (alkyl) 2, OH, alkoxy, aryloxy, SH, S-alkyl, S-aryl, alkyl of S02, S03H, SCF3, CN, halogen, CF3, N02, (CH2) tNR26R27 (wherein R26 and R27 are independently selected hydrogen, alkyl and alkanoyl) (t = 0 to 2), S02NH2, OCH2CH2NH2, OCH2CH2NHalkyl ?, OCH2CH2N (alkyl) 2, oxazolidin-2-yl, oxazolidin-2-yl substituted with alkyl, substituted or unsubstituted alkyl, heteroalkyl substituted or unsubstituted, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl. In an exemplary embodiment of the formula (VII), R1 is a substituted or unsubstituted aralkyl. In a further exemplary embodiment the substituted aralkyl has the structure wherein R28, R29, R30, R31 and R32 are defined as above, and neither is an integer selected from 1 to 15. In an exemplary embodiment of formula (VII), R1 is a substituted or unsubstituted heteroaryl. In one more exemplary embodiment thereof, heteroaryl has the structure wherein X is a member selected from CH = CH, N = CH, NR35 (where R35 = H, alkyl, aryl or benzyl), 0 or S. Y = CH or N. R33 and R34 are each independently selected members of H, haloalkyl, aralkyl, substituted aralkyl, (CH 2) U 0 H (wherein u = 1, 2 or 3), (CH 2) VNR 26 R 27 (wherein R 26 and R 27 are independently selected from hydrogen, alkyl and alkanoyl) (v = 0 to 3), C02H, C02alkyl, C0NH2, S-alkyl, S-aryl, S02alkyl, S03H, SCF3, CN, halogen, CF3, N02, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, heterocycloalkyl substituted or unsubstituted, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl. The structures of the invention also allow interactions with solvents that can give structures (formula Vllg) that include atoms derived from the solvent found by the compounds of the invention during synthetic manipulations and therapeutic uses. The Vllg structure originates from the formation of a dative bond between the solvents with the Lewis acid boron center. Thus, these solvent complexes can be stable entities with comparative bioactivities. These structures are expressly contemplated by the present invention wherein R *** is H or alkyl.

Formula (VHg) In an exemplary embodiment, the compound has a structure which is a member selected from 2- (3-chlorophenyl) - [1, 3, 2] -dioxoborlane, (3-chlorophenyl) (4'-fluoro- (2'-) acid. (methoxymethoxy) -methyl) -phenyl) -borinic acid, 1- (3-chlorophenyl) -5-fluoro-1,3-dihydrobenzo [c] [1,2] oxaborol, 1- (3-chlorophenyl) -6-fluoro -1, 3-dihydrobenzo [c] [1, 2] oxoborol, 1- (3-chlorophenyl) -1, 3-dihydrobenzo.c] (1, 2) oxaborol, 2- (3-fluorophenyl) - [1, 3,2] -dioxaborolane, 3- (benzo [c] [1,2] oxaborol-l (3H) -yl) benzonitrile, 2- (3-cyanophenyl) - [1,2,3] -dioxaborlane, acid ( 3-chlorophenyl) (5 '-fluoro- (2' - (methoxymethoxy) methyl) -phenyl) -borinic acid, 1- (3-chlorophenyl) -1,3-dihydro-3, 3-dimethylbenzo [c] [1, 2] oxaborol, (3-chlorophenyl) (2- (2- (methoxymethoxy) propan-2-yl) phenylboronic acid, 1- (3-chlorophenyl) -1,3-dihydro-3, 3-dimethylbenzo [c] [ 1, 2] oxaborol, 1- (4-chlorophenyl) -1,3-dihydrobenzo [c] [1,2] oxaborol, 2- (4-chlorophenyl) - [1, 3, 2] -dioxaborolane, 4- ( benzo [c] [1, 2] oxaborol-l (3H) -yl) ben zonitrile, 2- (4-cyanophenyl) - [1,3,2] -dioxaborolane, 4- (5-fluorobenzo [c] [1,2] oxaborol-1 (3H) -yl) benzonitrile, 2- (4- cyanophenyl) - [1, 3, 2] -dioxaborolane, 3- (5-fluorobenzo [c] [1, 2] oxaborol-1 (3H) -yl) benzonitrile, 2- (3-cyanophenyl) - [1,3 , 2] -dioxaborolane, 3- (6-fluorobenzo [c] [1, 2] oxaborol-l (3H) -yl) benzonitrile, 2- (3-cyanophenyl) - [1,3,2] -dioxaborolane, 1 - (3-cyanophenyl) -5,6-dimethoxy-1,3-dihydrobenzo [c] [1,2] -oxaborol, 2- (3-chlorophenyl) - [1,3,2] -dioxaborolane, (4- (5- (fluorobenzofc] [1, 2] oxaborol-1 (3H) -yl) phenylmethanamine, 5-fluoro-2- (methoxymethoxymethyl) phenyl] - [1,3,2] -dioxaborolane, 4- (5- ( fluorobenzo [c] [1,2] oxaborol-l (3H) -yl) phenylmethanamine, (3- (5- (fluorobenzo [c] [1,2] oxaborol-l (3H) -yl) -phenylmethanamine, (4 - (5- (fluorobenzo [c] [1,2] oxaborol-l (3H) -yl) phenyl) methanol, (3- (5- (fluorobenzo [c] [1,2] oxaborol-1 (3H) - il) phenyl) methanol, 3- (6-fluorobenzo [c] [1, 2] oxaborol-l (3H) -yl) phenyl, 3- (5-fluorobenzotc] [1,2] oxaborol-l (3H) - il) pyridine, (2- (benzo [c] [1,2] oxaborol-l (3H) -yl) phenyl) methanol, 2- [(methoxymethoxy) methyl] phenylboronic acid, 2- [(methoxymethoxymethyl) phenyl] - [1, 3, 2] -dioxaborolane, bis [2- (methoxymethoxymethyl) phenyl] boronic acid, (2- (benzo [c] [1,2] oxaborol-l (3H) -yl) phenyl) methanol, (2- (benzo [c] [ 1, 2] oxaborol-l (3H) -yl) -5-chlorophenyl) -N, N-dimethylmethanamine, (2- (benzo [c] [1,2] oxaborol-1 (3H) -yl) -5- chlorophenyl) methanol, (2- (benzo [c] [1,2] oxaborol-1 (3H) -yl) -5-chlorophenyl) methanol, (5-chloro-2- (5-chlorobenzo [c] [1, 2] oxaborol-1 (3H) -yl) phenyl) methanol, bis [4-chloro-2- (methoxymethoxymethyl) phenyl] borinic acid, (5-chloro-2- (5-chlorobenzo [c] (1, 2) oxaborol-l (3H) -yl) phenyl) methanol, (5-chloro-2- (5-chlorobenzo [c] [1, 2] oxaborol-1 (3H) -yl) phenyl-N, N-dimethylmethanamine, 1 - (4-chloro-2-methoxyphenyl) -1, 3-dihydrobenzofc] [1,2] benzoxazole, glycolic ester of 4-chloro-2-methoxyphenylboronic acid, 1- (4-chloro-2-methoxyphenyl) -1, 3-dihydrobenzo [c] [1,2] benzoxazole, 2- (benzo [c] [1,2] oxaboral-1 (3 H) -yl) -5-chlorophenol, 2- (3- (benzo [c] [1,2] oxaborol-1 (3 H) -yl) phenoxy) -5-chlorophenol, 2- (3- (benzo [c]) [1, 2] oxaborol-l (3H) -yl) phenoxy) -5-chlorophenol, 4- ((3- (5-fluorobenzo [c] [1, 2] oxaborol-1 (3H) -yl) phenyl) methyl) morpholine, 3- (5-fluorobenzo [c] [1, 2] oxaborol-l (3H) -yl] phenyl) -methyl, 8-hydroxy-quinoline-2-carboxylate, 1- (3-chlorophenyl) - 2,3-dihydro-2- (methoxymethyl) -lH-benzo [c] [1, 2] azaborol, 3-chlorophenyl 2- [N, -bis (methoxymethyl) aminomethyl] phenylboronic acid, 1- (3-chlorophenyl) -2, 3-dihydro-2- (methoxymethyl) -1H-benzo [c] [1,2] azaborol, 1- (3-chlorophenyl) -1, 3,4, 5-tetrahydrobenzo- [c] [1, 2] -oxaborepine, 1- (3-chlorophenyl) -1,3,4,5-tetrahydrobenzo [c] [1,2] oxaborepine, 1- (3-chlorophenyl) -3,4-dihydro-lH-benzo [ c] [1,2] -oxaborinin, 2- (3-chlorophenyl) - [1, 3, 2] dioxaborlane, (3-chlorophenyl) (2 '- (2- (methoxymethoxy) ethyl) phenyl) borinic acid and 1 - (3-chlorophenyl) -3,4-dihydro-lH-benzo [c] [1,2] oxoborinin. I. c. ) 2 '-Amino ribo uranosas In another aspect, the invention provides compounds useful in the methods which is 2'-amino ribofuranose. In an exemplary embodiment, the 1 'position of the ribofuranose is replaced with a member selected from substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl. In another exemplary embodiment, the 1 'position of the ribofuranose is substituted with a member selected from substituted or unsubstituted purine, substituted or unsubstituted pyrimidine, substituted or unsubstituted pyridine and substituted or unsubstituted imidazole. In another exemplary embodiment, the 1 'position of the ribofuranose is substituted with a member selected from substituted or unsubstituted nicotinic acid, substituted or unsubstituted nicotinamide, substituted or unsubstituted nucleic acid base, substituted or unsubstituted adenine, substituted or unsubstituted cytosine, substituted or unsubstituted guanine, substituted or unsubstituted thymine, unsubstituted or substituted uracil, substituted or unsubstituted N, N-dimethylguanine, substituted or unsubstituted dihydrouracil, substituted or unsubstituted 4-thiouridine and substituted inopine or not replaced. In another exemplary embodiment, the compound has a structure according to the order (VI I I): wherein L is a member selected from substituted or unsubstituted purine, substituted or unsubstituted pyrimidine, substituted or unsubstituted pyridine and substituted or unsubstituted imidazole. M, as defined above, is a member selected from O, S and NR2. R40 and R41 are each members independently selected from H, aralkyl, substituted aralkyl, (CH2) sOH (where s = 3), C02H, C02 alkyl, C (0) NH2, C (O) NHalkyl, CON ( alkyl) 2, C (0) R23, OH, alkoxy, aryloxy, SH, S-alkyl, S-aryl, alkyl of S02, S03H, SCF3, CN, halogen, CF3, N02, (CH2) NR26R27 (wherein R26 and R27 are independently selected from hydrogen, alkyl and alkanoyl) (t = 0 to 2), S02NH2, OCH2CH2NH2, OCH2CH2NHalkyl, OCH2CH2N (alkyl) 2, oxazolidin-2-yl, oxazolidin-2-yl substituted with alkyl, substituted alkyl or unsubstituted, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, R43 < R and R45 are each members independently selected from substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl. R43 and R44, together with the atoms to which they are attached, optionally join to form a 4- to 7-membered ring. R43 and R45, together with the atoms to which they are attached, optionally join to form a 4- to 7-membered ring. R44 and R45, together with the atoms to which they are attached, optionally join to form a 4 to 7 membered ring. A, D, E and G are all defined anywhere in the present. Z is a member selected from CR46 and N. The combinations of nitrogens (A + D + E + G + Z) is an integer selected from 0 to 4. At least two members selected from R9, R10, R11, R12 and R46, together with the atoms to which they are attached, they optionally join to form a ring of 4 to 7 members. In an exemplary mode, it is a member selected from: In another exemplary embodiment, the compound has a formula according to the following formulas: (VlUa) and (VlIIb) In an emplar modality, the compound is a member selected from: (D3); I. d. 3 '- Fibrous amino-ribose In another aspect, the invention provides compounds useful in the methods which are a 3'-aminofuranose. In an exemplary embodiment, the 1 'position of the ribofuranose is substituted with a member selected from substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl. In another exemplary embodiment, the 1 'position of the ribofuranose is substituted with a member selected from substituted or unsubstituted purine, substituted or unsubstituted pyrimidine, substituted or unsubstituted pyridine and substituted or unsubstituted imidazole. In another exemplary embodiment, the 1 'position of the ribofuranose is substituted with a member selected from substituted or unsubstituted nicotinic acid, substituted or unsubstituted nicotinamide, substituted or unsubstituted nucleic acid base, substituted or unsubstituted adenine substituted, substituted or unsubstituted, substituted or unsubstituted guanine, substituted or unsubstituted thymine, unsubstituted or substituted uracil, substituted or unsubstituted N, N-dimethylguanine, substituted or unsubstituted dihydrouracil, unsubstituted or substituted 4-thiouridine and inopine replaced or not replaced. In another exemplary embodiment, the compound has a structure according to formula (VIIIc): L R41 ^ - OH R (VIIIc) wherein L is a member selected from substituted or unsubstituted purine, substituted or unsubstituted pyrimidine, substituted or unsubstituted pyridine and substituted or unsubstituted imidazole. M, as defined above, is a member selected from O, S and NR2. R40 and R41 are each members independently selected from H, aralkyl, substituted aralkyl, (CH2) sOH (where s = 3), C02H, C02 alkyl, C (0) NH2, C (O) NHalkyl, CON ( alkyl) 2, C (O) R23, OH, alkoxy, aryloxy, SH, S-alkyl, S-aryl, alkyl of S02, S03H, SCF3, CN, halogen, CF3, N02, (CH2) tNR26R27 (wherein R26 and R27 are independently selected from hydrogen, alkyl and alkanoyl) (t = 0 to 2), S02NH2, OCH2CH2NH2, OCH2CH2NHalkyl, OCH2CH2N (alkyl) 2, oxazolidin-2-yl, oxazolidin-2-yl substituted with alkyl, substituted alkyl or unsubstituted, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, R43, R44 and R45 are each members independently selected from substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl. R43 and R44, together with the atoms to which they are attached, optionally join to form a 4- to 7-membered ring. R43 and R45, together with the atoms to which they are attached, optionally join to form a 4- to 7-membered ring. R44 and R45, together with the atoms to which they are attached, optionally join to form a 4 to 7 membered ring. A, D, E and G are all defined anywhere in the present. Z is a member selected from CR46 and N. The combinations of nitrogens (A + D + E + G + Z) is an integer selected from 0 to 4. At least two members selected from R9, R10, R11, R12 and R46, together with the atoms to which they are attached, they optionally join to form a 4 to 7 member ring. n select member In another exemplary embodiment, the compound has a formula according to the following formulas: (Vine) In an exemplary embodiment, the compound is a member selected from: T. Acrylic acids and Acronic Boronic Esters, part I Acyclic boronic acids and esters such as those described in this section may also be used in the invention. These compounds can be used to kill or inhibit the growth of microorganisms described herein, as well as to treat the diseases described herein. In addition, these compounds can be used as synthetic intermediates in the generation of the compounds described herein. In another aspect, the compound has a structure according to the following formula: wherein R1 and R2 are members independently selected from H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl. R1 and R2, together with the atoms to which they are attached, can optionally be attached to form a 4 to 7 membered ring. Zl is a selected member of wherein each R3a and R4a is a member independently selected from H, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted or non-substituted heteroaryl replaced. R5 is a member selected from halogen and OR6. R6 is a member selected from H, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl. A is a selected member of CR9a and N. D is a selected member of CR10a and N. E is a selected member of CRlla and N. G is a selected member of CR12a and N. R9a, R10a, Rlla and R12a are members independently selected from H, OR *, NR * R **, SR *, -S (0) R *, -S (0) 2R *, -S (0) 2NR * R * *, -C (0) R *, -C (0) OR *, -C (0) NR * R **, nitro, halogen, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted cycloalkyl or unsubstituted, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl. Each R * and R ** is a member independently selected from H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl . R9a and R10a, together with the atoms to which they are attached, optionally join to form a ring. R10a and Rlla, together with the atoms to which they are attached, optionally join to form a ring. Rlla and R12a, together with the atoms to which they are attached, optionally join to form a ring. The combination of nitrogens (A + D + E + G) is an integer selected from 0 to 3. In an exemplary embodiment, there is a condition that the compound is not a member selected from: In an exemplary embodiment, the compound has a structure according to formula IXa In another exemplary embodiment, each R3a and Ra is a member independently selected from H, cyano, substituted or unsubstituted methyl, substituted or unsubstituted ethyl, trifluoromethyl, substituted or unsubstituted hydroxymethyl, substituted or unsubstituted hydroxyalkyl, substituted or unsubstituted benzyl. , substituted or unsubstituted phenyl, unsubstituted or substituted mercaptomethyl, substituted or unsubstituted mercaptoalkyl, substituted or unsubstituted aminomethyl, unsubstituted or substituted alkylaminomethyl, unsubstituted or substituted dialkylaminomethyl, unsubstituted or substituted arylaminomethyl, unsubstituted or substituted indolyl and amido replaced or not replaced. In another exemplary embodiment, each R3a and Ra is a member independently selected from cyano, substituted or unsubstituted methyl, substituted or unsubstituted ethyl, trifluoromethyl, substituted or unsubstituted hydroxymethyl, substituted or unsubstituted hydroxyalkyl, substituted or unsubstituted benzyl, phenyl substituted or unsubstituted, substituted or unsubstituted mercaptomethyl, substituted or unsubstituted mercaptoalkyl, substituted or unsubstituted aminomethyl, substituted or unsubstituted alkylaminomethyl, substituted or unsubstituted dialkylaminomethyl, substituted or unsubstituted arylaminomethyl, unsubstituted or substituted indolyl, substituted amido or not replaced In another exemplary embodiment, each R3a and Ra is a member selected from H, substituted or unsubstituted methyl, substituted or unsubstituted ethyl, substituted or unsubstituted propyl, substituted or unsubstituted isopropyl, substituted or unsubstituted butyl, substituted t-butyl. or unsubstituted, substituted or unsubstituted phenyl, and substituted or unsubstituted benzyl. In another exemplary embodiment, R3a and R4a is a member selected from methyl, ethyl, propyl, isopropyl, butyl, t-butyl, phenyl and benzyl. In another exemplary embodiment, R3a is H and R4a is a member selected from methyl, ethyl, propyl, isopropyl, butyl, t-butyl, phenyl and benzyl. In another exemplary embodiment, R3a is H and R4a H. In another exemplary embodiment Z1 is CHO. In another exemplary mode, Zl is wherein R5 is a member selected from OH, substituted or unsubstituted methoxy, substituted or unsubstituted ethoxy, substituted or unsubstituted methoxymethoxy, substituted or unsubstituted ethoxyethoxy, substituted or unsubstituted trialkylsiallyl, and tetrahydro-2H-pyran-2-yloxy replaced or not replaced. In another exemplary embodiment, R5 is unsubstituted or substituted trialkylsiallyl, wherein the trialkylsilyl is a member selected from unsubstituted or substituted trimethylsilyl, substituted or unsubstituted tert-butyldimethylsilyl and substituted or unsubstituted tributylsilyl. In another exemplary embodiment, R 5 is unsubstituted or substituted methoxy, substituted or unsubstituted ethoxy, substituted or unsubstituted methoxymethoxy, substituted or unsubstituted ethoxyethoxy and unsubstituted or substituted tetrahydro-2H-pyran-2-yloxy. In another exemplary embodiment, R5 is a member selected from methoxy, ethoxy, methoxymethoxy, ethoxyethoxy and tetrahydro-2H-pyran-2-yloxy. In another exemplary mode, Zl is In an exemplary embodiment, R9a, R10a, Rlla and R12a is a member selected independently from H, OR *, NR * R **, SR *, -S (0) R *, -S (0) 2R *, -S (0) 2NR * R **, -C (0) R *, -C (0) OR *, -C (0) NR * R **, halogen, cyano, nitro, substituted or unsubstituted methoxy, substituted methyl or unsubstituted, substituted or unsubstituted ethoxy, unsubstituted or substituted ethyl, trifluoromethyl, substituted or unsubstituted hydroxymethyl, substituted or unsubstituted hydroxyalkyl, substituted or unsubstituted benzyl, substituted or unsubstituted phenyl, unsubstituted or substituted phenyloxy, substituted phenylmethoxy or unsubstituted, substituted or unsubstituted thiophenyloxy, substituted or unsubstituted pyridinyloxy, substituted or unsubstituted pyrimidinyloxy, substituted or unsubstituted benzylfurany, unsubstituted or substituted methylcyanide, Mercaptomethyl substituted or unsubstituted mercaptoalkyl substituted or unsubstituted, substituted or unsubstituted phenylthio, substituted or unsubstituted tiofeniltio, substituted or unsubstituted phenylmethylthio, substituted or unsubstituted pyridinylthio, substituted or unsubstituted pyrimidinylthio, substituted benciltiofuranilo or unsubstituted phenylsulfonyl substituted or unsubstituted, substituted benzylsulfonyl or unsubstituted, substituted phenylmethyl or unsubstituted tiofenilsulfonilo substituted or unsubstituted pyridinylsulfonyl substituted or unsubstituted, pirimidinilsulfonilo substituted or unsubstituted sulfonamidyl substituted or unsubstituted, substituted phenylsulfinyl or unsubstituted, substituted benzylsulfinyl or unsubstituted, substituted or unsubstituted phenylmethylsulfinyl, substituted or unsubstituted thiophenylsulfinyl, substituted or unsubstituted pyridinyl-sulfinyl, substituted or unsubstituted pyrimidinyl-sulfinyl, unsubstituted or substituted amino, unsubstituted or substituted alkylamino ituido, substituted or unsubstituted dialkylamino, substituted trifluoromethylamino or unsubstituted, substituted or unsubstituted aminomethyl, substituted or unsubstituted alkylaminomethyl, substituted or unsubstituted dialkylaminomethyl, substituted or unsubstituted arilaminometilo, substituted or unsubstituted benzylamino, substituted phenylamino or unsubstituted, unsubstituted or substituted thiophenylamino, substituted or unsubstituted pyridinylamino, substituted or unsubstituted pyrimidinylamino, unsubstituted or substituted indolyl, substituted or unsubstituted morpholino, substituted or unsubstituted alkylamido, substituted or unsubstituted arylamido, unsubstituted or substituted ureido, substituted carbamoyl or unsubstituted, and substituted or unsubstituted piperizinyl. In an exemplary embodiment, R9a, R10a, Rlla and R12a are selected from the above list of substituents with the exception of -C (0) R *, -C (0) OR *, -C (0) NR * R **. In another exemplary embodiment, R9a, R10a, Rlla and R12a are members independently selected from fluoro, chloro, bromo, nitro, cyano, amino, methyl, hydroxylmethyl, trifluoromethyl, methoxy, trifluoromethoxy, ethyl, diethylcarbamoyl, pyridin-2-yl, pyridin. -3-yl, pyridin-4-yl, pyrimidinyl, piperazino, piperizinyl, piperizinocarbonilo, piperizinilcarbonilo, carboxyl, 1-tetrazolyl, 1-ethoxycarbonylmethoxy, carboxymethoxy, thiophenyl, 3- yl lH-tetrazol-5-(butylcarbonyl) phenylmethoxy, 1-etoxicarbonilmetiloxi-, 1-etoxicarbonilmetilo-, 1-etoxicarbonilo-, carboximetoxi-, thiophen-2-iltio-, thiophen-3-yl, thiophen-3-ylthio, 4-fluorophenylthio, butilcarbonilfenilmetoxi, thiophen-2-yl I butilcarbonilfenilmetilo , butylcarbonylmethyl, 1- (piperidin-1-yl) carbonyl) methyl, 1- (piperidin-1-yl) carbonyl) methoxy, 1- (piperidin-2-yl) carbonyl) methoxy, 1- (piperidin-3-yl) ) carbonyl) methoxy, 1- (4- (pyrimidin-2-yl) piperazin-1-yl) carbonyl) methoxy, 1- (4- (pyrimidin-2-yl) piperazin-1-yl) carbonyl) methyl, - (4- (pyrimid in-2-yl) piperazin-1-yl) carbonyl, 1-4- (pyrimidin-2-yl) piperazin-1-yl, 1- (4- (pyridin-2-yl) piperazin-1-yl) carbonyl ), 1- (4- (pyridin-2-yl) piperazin-1-yl) carbonylmethyl, (1- (4- (pyridin-2-yl) piperazin-1-yl) carbonyl) -methoxy), 1- ( 4- (pyridin-2-yl) piperazin-1-yl, 1H-indol-1-yl, morpholino-, morpholinyl, morpholinocarbonyl, morpholinylcarbonyl, phenylureido, phenylcarbamoyl, acetamide, 3- (phenylthio) -lH-indole-1- ilo, 3- (2-cyanoethylthio) -lH-indol-1-yl, benzylamino, 5-methoxy-3- (phenylthio) -lH-indol-1-yl, 5-methoxy-3- (2-cyanoethylthio) - lH-indol-1-yl)), 5-chloro-lH-indol-1-yl, 5-chloro-3- (2-cyanoethylthio) -lH-indol-1-yl), dibenzylamino, benzylamino, 5- chloro-3- (phenylthio) -lH-indol-1-yl)), 4- (lH-tetrazol-5-yl) phenoxy, 4- (lH-tetrazol-5-yl) phenyl, 4- (lH-tetrazole -5-yl) phenylthio, 2-cyanophenoxy, 3-cyanophenoxy, 4-cyanophenoxy, 2-cyanophenylthio, 3-cyanophenylthio, 4-cyanophenylthio, 2-chlorophenoxy, 3-chlorophenoxy, 4-chlorophenoxy, 2-fluorophenoxy, 3-fluorophenoxy , 4-fluorophenoxy, 2-cyano benzyloxy, 3-cyanobenzyloxy, 4-cyanobenzyloxy, 2-chlorobenzyloxy, 3-chlorobenzyloxy, 4-chlorobenzyloxy, 2-fluorobenzyloxy, 3-fluorobenzyloxy, 4-fluorobenzyloxy, unsubstituted phenyl, unsubstituted benzyl. In an exemplary embodiment, R9a is H and R12a is H. In an exemplary embodiment, the compound has a combination of substituents for R9a, R10a, Rlla and R12a which is a member selected from those described in formulas (I), (the ), (Ib), (le), (Id), (le), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (II), (Im), (In), (lo), (ip), iq), (go), (Is), (It), (Iu), (Iv), (Iw), (Iz), (Iaa), (Lab) , (lac), (lad), (Iae), (laf), (lag), (Iah), (Iai), (Iaj), (Iak), above, and / or the subsequent paragraphs that describe the formulas ( I), (la), (Ib), (le), (Id), (le), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (II) , (im), (in), (lo), (Ip), Iq), (Ir), (Is), (It), (Iu), (Iv), (I), (Iz), (laa) ), (Lab), (lac), (lad), (Iae), (Iaf), (Iag), (Iah), (Iai), (Iaj), (Iak). In an exemplary embodiment, the compound is an acyclic boronic acid or ester in which a portion of the acyclic boronic acid or ester as in Figure (IXb) below is a member selected from a structure in Figures 12A-12I. In another exemplary embodiment, the compound is a dimer, anhydride or trimer of an acyclic boronic acid or ester described herein. In another exemplary embodiment, the compound is a dimer, anhydride or trimer of an acyclic boronic acid or ester in which a portion of the acyclic ester or boronic acid as in Figure (IXb) is a member selected from a structure in Figures 12A -12I. In an exemplary embodiment, R1 and R2 are each members independently selected from H, substituted or unsubstituted methyl, substituted or unsubstituted ethyl, substituted or unsubstituted propyl, substituted or unsubstituted isopropyl, substituted or unsubstituted butyl, t-butyl substituted or unsubstituted, substituted or unsubstituted phenyl and substituted or unsubstituted benzyl. R1 and R2, together with the atoms to which they are attached, can optionally form a member selected from substituted or unsubstituted dioxaborolane, substituted or unsubstituted dioxaborin, and substituted or unsubstituted dioxaborepane. In an exemplary embodiment, R1 and R2 are each members independently selected from H, methyl, ethyl, propyl, isopropyl, butyl, t-butyl, phenyl and benzyl. In an exemplary embodiment, R1 and R2 are each members independently selected from H, methyl, isopropyl and phenyl. In an exemplary embodiment, R1 and R2 are methyl. In an exemplary embodiment, R1 and R2 are isopropyl. In an exemplary embodiment, R1 and R2 are H. In another exemplary embodiment, R1 and R2, together with the atoms to which they are attached, form a member selected from substituted or unsubstituted dioxaborolane, substituted or unsubstituted dioxaborin, and substituted dioxaborepane or not replaced In another exemplary embodiment, R1 and R2, together with the atoms to which they are attached, form a member selected from dioxaborolane, substituted or unsubstituted tetramethyldioxaborolane, substituted or unsubstituted phenylimodioxazole, dioxaborinone, dimethyldioxaborinone and dioxaborepane. In an exemplary embodiment, the compound is a member selected from In an exemplary embodiment, the compound is a member selected from: In an exemplary embodiment, the compound is a member selected from In another exemplary embodiment, the compounds and embodiments described herein can form a hydrate with water, a solvate with an alcohol (for example methanol, ethanol, propanol); an adduct with an amino compound (eg, ammonia, methylamine, ethylamine); an adduct with an acid (for example, formic acid, acetic acid); complexes with ethanolamine, quinoline, amino acids and the like. In an exemplary embodiment, the acyclic boronic esters described herein can be used as intermediates in the synthesis of the compounds described herein. In another exemplary embodiment, the acyclic boronic esters described herein can be used as intermediates in the synthesis of a compound that is a member selected from formulas (I), (a), (Ib), (le), (id), de), (if), dg), (ih), (ii), dj), (ik), (11), (im), (in), (lo), (Ip), Iq ), (Go), (Is), (It), (Iu), (Iv), (Iw), (iz), (iaa), (Lab), (Iac), (Iad), (Iae), (laf), (iag), (Iah), (Iai), (Iaj), (Iak). I. f. Acyclic Boronic Acids and Acids, part II The acyclic boronic acids and esters described herein may also be used in the invention. These compounds can be used to kill or inhibit the growth of the microorganisms described herein, as well as to treat the diseases described herein. In addition, these compounds can be used as synthetic intermediates in the generation of other compounds described herein. In an exemplary embodiment, these other compounds are cyclic boronic esters and cyclic boronic esters described herein. In another aspect, the compound has a structure according to the following formula: wherein R1 and R2 are members independently selected from H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl. R1 and R2, together with the atoms to which they are attached, can optionally be attached to form a 4 to 7 membered ring. X is a member selected from substituted or unsubstituted triflate, halogen, substituted or unsubstituted sulphonic esters and substituted or unsubstituted acyloxy groups, and substituted or unsubstituted diazo. R3a and Ra are members independently selected from H, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl. A is a selected member of CR9 and N. D is a selected member of CR10a and N. E is a selected member of CRlla and N. G is a selected member of CR12a and N. R9a, R10a, Rlla and R12a are selected members independently of H, OR *, NR * R **, SR *, -S (0) R *, -S (0) 2R *, -S (0) 2NR * R **, -C (0) R * , -C (0) OR *, -C (0) NR * R **, nitro, halogen, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl. Each R * and R ** is a member independently selected from H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl . R10a and Rlla, together with the atoms to which they are attached, optionally join to form a ring. R10a and Rlla, together with the atoms to which they are attached, optionally join to form a ring. Rlla and R12a, together with the atoms to which they are attached, optionally join to form a ring. The combination of nitrogens (A + D + E + G) is an integer selected from 0 to 3. In an exemplary embodiment, this aspect has the proviso that the compound is not: In an exemplary embodiment, the compound has a structure according to the formula (Xa) In another exemplary embodiment, each R3a and R4a is a member independently selected from H, cyano, substituted or unsubstituted methyl, substituted or unsubstituted ethyl, trifluoromethyl, substituted or unsubstituted hydroxymethyl, substituted or unsubstituted hydroxyalkyl, substituted or unsubstituted benzyl. , substituted or unsubstituted phenyl, unsubstituted or substituted mercaptomethyl, substituted or unsubstituted mercaptoalkyl, substituted or unsubstituted aminomethyl, unsubstituted or substituted alkylaminomethyl, unsubstituted or substituted dialkylaminomethyl, unsubstituted or substituted arylaminomethyl, unsubstituted or substituted indolyl and amido replaced or not replaced. In another exemplary embodiment, each R3a and R4a is a member independently selected from cyano, substituted or unsubstituted methyl, substituted or unsubstituted ethyl, trifluoromethyl, substituted or unsubstituted hydroxymethyl, substituted or unsubstituted hydroxyalkyl, substituted or unsubstituted benzyl, phenyl substituted or unsubstituted, substituted or unsubstituted mercaptomethyl, substituted or unsubstituted mercaptoalkyl, substituted or unsubstituted aminomethyl, substituted or unsubstituted alkylaminomethyl, substituted or unsubstituted dialkylaminomethyl, substituted or unsubstituted arylaminomethyl, unsubstituted or substituted indolyl, substituted amido or not replaced In another exemplary embodiment, each R3a and R4a is a member selected from H, substituted or unsubstituted methyl, substituted or unsubstituted ethyl, substituted or unsubstituted propyl, substituted or unsubstituted isopropyl., substituted or unsubstituted butyl, substituted or unsubstituted t-butyl, substituted or unsubstituted phenyl and substituted or unsubstituted benzyl. In another exemplary embodiment, R3a and R4a is a member selected from methyl, ethyl, propyl, isopropyl, butyl, t-butyl, phenyl and benzyl. In another exemplary embodiment, R3a is H and R4a is a member selected from methyl, ethyl, propyl, isopropyl, butyl, t-butyl, phenyl and benzyl. In another exemplary embodiment, R3a is H and R4a H. In another exemplary embodiment, R9a, R10a, Rlla and R12a is a member selected from H, OR *, NR * R **, SR *, -S (0) R * , -S (0) 2R *, -S (0) 2NR * R **, -C (0) R *, -C (0) OR *, -C (0) NR * R **, halogen, cyano , nitro, substituted or unsubstituted methoxy, substituted or unsubstituted methyl, substituted or unsubstituted ethoxy, substituted or unsubstituted ethyl, trifluoromethyl, substituted or unsubstituted hydroxymethyl, substituted or unsubstituted hydroxyalkyl, substituted or unsubstituted benzyl, substituted phenyl or unsubstituted, substituted or unsubstituted phenyloxy, substituted or unsubstituted phenylmethoxy, substituted or unsubstituted thiophenyloxy, substituted or unsubstituted pyridinyloxy, substituted or unsubstituted pyrimidinyloxy, unsubstituted or substituted benzylfuran, substituted or unsubstituted methylthio, unsubstituted or substituted mercaptobenzyl , substituted or unsubstituted mercaptoalkyl, phenylthio substituted or not substituted substituted, substituted or unsubstituted thiophenylthio, substituted or unsubstituted phenylmethylthio, substituted or unsubstituted pyridinylthio, substituted or unsubstituted pyrimidinylthio, unsubstituted or substituted benzylthiuram, unsubstituted or substituted phenylsulfonyl, unsubstituted or substituted benzylsulfonyl, substituted or unsubstituted phenylmethylsulfonyl, unsubstituted or substituted thiophenylsulfonyl, substituted or unsubstituted pyridinyl, substituted or unsubstituted pyrimidinylsulfonyl, substituted or unsubstituted sulfonamidyl, substituted or unsubstituted phenylsulfinyl, unsubstituted or substituted benzylsulfinyl, unsubstituted or substituted phenylmethylsulphinyl, substituted or unsubstituted thiophenylsulfinyl, substituted pyridinylsulfinyl or unsubstituted, substituted or unsubstituted amino, substituted or unsubstituted alkylamino, substituted or unsubstituted dialkylamino, substituted or unsubstituted trifluoromethylamino, substituted or unsubstituted aminomethyl, substituted or unsubstituted alkylaminomethyl substituted, substituted or unsubstituted dialkylaminomethyl, substituted or unsubstituted arylaminomethyl, substituted or unsubstituted benzylamino, substituted or unsubstituted phenylamino, substituted or unsubstituted thiophenylamino, substituted or unsubstituted pyridinylamino, substituted or unsubstituted pyridinylamino, substituted or unsubstituted indolyl, unsubstituted or substituted morpholino, unsubstituted or substituted alkylamido, unsubstituted or substituted arylamido, unsubstituted or substituted ureido, substituted or unsubstituted carbamoyl and substituted or unsubstituted pipericinyl. In an exemplary embodiment, R9a, R10a, Rlla and R12a are selected from the foregoing list of substituents with the exception of -C (0) R *, -C (0) 0R *, -C (0) NR * R **. In another exemplary embodiment, R9a, R10a, Rlla and R12a are members independently selected from fluoro, chloro, bromo, nitro, cyano, amino, methyl, hydroxylmethyl, trifluoromethyl, methoxy, trifluoromethoxy, ethyl, diethylcarbamoyl, pyridin-2-yl, pyridin. -3-yl, pyridin-4-yl, pyrimidinyl, piperazino, piperizinyl, piperizinocarbonyl, piperizinylcarbonyl, carboxyl, 1-tetrazolyl, 1-ethoxycarbonylmethoxy, carboxymethoxy, thiophenyl, 3- (butylcarbonyl) phenylmethoxy, lH-tetrazol-5-yl, 1-Ethoxycarbonylmethyloxy-, 1-ethoxycarbonylmethyl-, 1-ethoxycarbonyl-, carboxymethoxy-, thiophen-2-yl, thiophen-2-ylthio-, thiophen-3-yl, thiophen-3-ylthio, 4-fluorophenylthio, butylcarbonylphenylmethoxy, butylcarbonylphenylmethyl , butylcarbonylmethyl, 1- (piperidin-1-yl) carbonyl) methyl, 1- (piperidin-1-yl) carbonyl) methoxy, 1- (piperidin-2-yl) carbonyl) methoxy, 1- (piperidin-3-yl) ) carbonyl) methoxy, 1- (4- (pyrimidin-2-yl) piperazin-1-yl) .carbonyl) methoxy, 1- (4- (pyrimidin-2-yl) piperazin-1-yl) carbonyl) ethyl, 1- (4- (piri midin-2-yl) piperazin-1-yl) carbonyl, 1-4- (pyrimidin-2-yl) piperazin-1-yl, 1- (4- (pyridin-2-yl) piperazin-1-yl) carbonyl ), 1- (4- (pyridin-2-yl) piperazin-1-yl) carbonylmethyl, 1- (4- (pyridin-2-yl) piperazin-1-yl) carbonyl) -methoxy), - (4- (pyridin-2-yl) piperazin-1-yl, lH-indol-1-yl, morpholino-, morpholinyl, morpholinocarbonyl, morpholinylcarbonyl, phenylureido, phenylcarbamoyl, acetamide, 3- (phenylthio) -lH-indole- 1-yl, 3- (2-cyanoethylthio) -lH-indol-1-yl, benzylamino, 5-methoxy-3- (phenylthio) -lH-indol-1-yl, 5-methoxy-3- (2-cyanoethylthio) ) -lH-indol-1-yl)), 5-chloro-lH-indol-1-yl, 5-chloro-3- (2-cyanoethyl-thio) -1H-indolyl)), dibenzylamino, benzylamino, 5-chloro-3- (phenylthio) -1H-indol-1-yl)), 4- (lH-tetrazol-5-yl) phenoxy, 4- (lH-tetrazol-5-yl) phenyl, 4- (lH -tetrazol-5-yl) phenylthio, 2-cyanophenoxy, 3-cyano-phenoxy, 4-cyano-phenoxy, 2-cyanophenyl thio, 3-cyano-phenyl-3, 4-cyano-phenyl, 2-chlorophenoxy, 3-chlorophenoxy, 4-chlorophenoxy, 2-fluorophenoxy , 3 - fluorofenox i, 4-fluorophenoxy, 2-cyanobenzyloxy, 3-cyanobenzyloxy, 4-cyanobenzyloxy, 2-chlorobenzyloxy, 3-chlorobenzyloxy, 4-chlorobenzyloxy, 2-fluorobenzyloxy, 3-fluorobenzyloxy, 4-fluorobenzyloxy, unsubstituted phenyl, unsubstituted benzyl. In an exemplary mode, R9a is H and R12a is H. In an exemplary embodiment, the compound has a combination of substituents for R9a, R10a, Rlla and R12a which is a member selected from those described in formulas (I), (Ia), (Ib) ), (le), (Id), (le), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (II), (Im), (In), (lo), (Ip), Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Iz), (Iaa), (Lab), (lac) , (lad), (Iae), (Iaf), (lag), (Iah), (Iai), (Iaj), (Iak), above, and / or the subsequent paragraphs that describe formulas (I), (the ), (Ib), (le), (Id), (le), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (II), (Im), (In), (lo), (Ip), Iq), (Ir), (Is), (It), (Iu), (Iv), (Iw), (Iz), (Iaa), (Lab) , (lac), (lad), (iae), (laf), (lag), (Iah), (Iai), (Iaj), (Iak). In an exemplary embodiment, the compound is an acyclic boronic acid or ester in which a portion of the acyclic boronic acid or ester is as in Figure (ixb) below. is a member selected from a structure in Figures 12A-12I. In another exemplary embodiment, the compound is a dimer, anhydride or trimer of an acyclic boronic acid or ester described herein. In another exemplary embodiment, the compound is a dimer, anhydride or trimer of an acyclic boronic acid or ester in which a portion of the acyclic boronic acid or ester as in Figure (IXb) is a member selected from a structure in Figure 12. In an exemplary embodiment, R1 and R2 are each members independently selected from H, substituted or unsubstituted methyl, substituted or unsubstituted propyl, substituted or unsubstituted isopropyl, substituted or unsubstituted butyl, substituted or unsubstituted t-butyl, substituted or unsubstituted phenyl and unsubstituted or substituted benzyl. R1 and R2, together with the atoms to which they are attached, can optionally form a member selected from substituted or unsubstituted dioxaborolane, substituted or unsubstituted dioxaborin, or substituted or unsubstituted dioxaborepane. In an exemplary embodiment, X is a member selected from triflate, chlorine, bromine, iodine, substituted or unsubstituted sulphonic esters, substituted or unsubstituted acyloxy groups and substituted or unsubstituted diazo. In an exemplary embodiment, X is a sulphonic ester group, which is a member selected from substituted or unsubstituted mesylate, substituted or unsubstituted tosylate, substituted or unsubstituted brosylate and substituted or unsubstituted nosylate. In an exemplary embodiment, X is an acyloxy group, which is a member selected from substituted or unsubstituted acetoxy, and trifluoroacetoxy substituted or unsubstituted. In another exemplary embodiment, X is a member selected from bromine, iodine, mesylate and diazo. In another exemplary embodiment, X is a selected member of bromine and iodine. In another exemplary embodiment, R1 and R2, together with the atoms to which they are attached, form a member selected from dioxaborolane, substituted or unsubstituted tetramethyldioxaborolane, substituted or unsubstituted phenyldioxaborolane, dioxaborin, dimethyldioxaborin, and dioxaborepane. In another exemplary embodiment, R3a and R4a are each members selected from H, methyl, ethyl, propyl, butyl, phenyl, benzyl, cyano, halogen and nitro. In an exemplary embodiment, the compound is a member selected from In an exemplary embodiment, the compound is a member selected from In an exemplary embodiment, the acyclic boronic esters described herein can be used as intermediates in the synthesis of the compounds described herein. In another exemplary embodiment, the acyclic boronic esters described herein may be used as intermediates in the synthesis of a compound that is a member selected from formulas (I), (a), (Ib), (le), (id) ), (le), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (II), (Im), (In), (lo), (Ip), Iq), (ir), (Is), (It), (Iu), (Iv), (Iw), (iz), (iaa), (Lab), (Iac), dad), (Iae), (Iaf), (lag), (Iah), (lai), (iaj), (Iak). I. e. ) Additional compounds Compounds such as those described herein may also be used in the invention. The compounds of the invention can form between the 2 A 3 'diol of the ribose ring of a nucleic acid, nucleoside or nucleotide, and a cyclic or acyclic boronic ester such as those described herein. These compounds can be used in a human or an animal to kill or inhibit the growth of the microorganisms described herein, as well as to treat the diseases described herein. These compounds can be formed in vi tro as well as in vivo. The methods for making these compounds are given in the examples section. In another aspect, the invention provides a compound having a structure according to the following formula: where B is boron. L is a member selected from OR7, substituted or unsubstituted purine, substituted or unsubstituted pyrimidine, substituted or unsubstituted pyridine and substituted or unsubstituted imidazole. R7 is a member selected from H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl. A is a member selected from OH, substituted or unsubstituted monophosphate, and substituted or unsubstituted phosphate, substituted or unsubstituted triphosphate, nucleic acid sequence comprising between 1 and 100 nucleotides. Q is a member selected from substituted or unsubstituted heterocycloalkyl and substituted or unsubstituted heteroaryl. Q comprises boron and at least one oxygen. In an exemplary embodiment, the aspect has the proviso that the compound can not comprise a selected member of C1-C40. In an exemplary embodiment, the aspect has a condition that the compound can not comprise a member that is described in Figure 1. In an exemplary embodiment, the aspect has a condition that the compound can not include a compound that is described in the US patent No. 5,880,188 expired. In an exemplary embodiment, the compound has a structure according to the following formula (Xlla): where is a member selected from O and S. J is a member selected from (CR3aR4a) n? And CR5a, R3a, R4a and R5a are members independently selected from H, halogen, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, aryl substituted or unsubstituted and substituted or unsubstituted heteroaryl. Neither is an integer selected from 0 to 2. It is a member selected from C = 0 (carbonyl), (CR6AR7a) m and CR8a. R6a, R7a and R8a are members independently selected from H, halogen, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl replaced. The ml index is an integer selected from 0 and 1. A is a selected member of CR9a and N. D is a selected member of CR10a and N. E is a selected member of CRlla and N. G is a selected member of CR1 a N. R9a, R10a, Rlla and R12a are members independently selected from H, OR *, NR * R **, SR *, -S (0) R *, -S (0) 2R *, -S (0) 2NR * R **, -C (0) R *, -C (0) 0R *, -C (0) NR * R **, nitro, halogen, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, unsubstituted or substituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl. Each R * and R ** are members independently selected from H, nitro, halogen, cyano, substituted or unsubstituted algeryl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl. The combination of nitrogens (A + D + E + G) is an integer selected from 0 to 3. A selected member of R3a, Ra and R5a and a selected member of R6a, R7a and R8a, together with the atoms to which they are united, they are optionally joined to form a ring of 4 to 7 members. R3a and R4a, together with the atoms to which they are attached, optionally join to form a 4 to 7 membered ring. R6a and R7a, together with the atoms to which they are attached, optionally join to form a 4 to 7 membered ring. R9a and R10a, together with the atoms to which they are attached, optionally join to form a 4- to 7-membered ring. R10a and Rlla, together with the atoms to which they are attached, optionally join to form a 4 to 7 membered ring. Rlla and R1a, together with the atoms to which they are attached, optionally join to form a 4- to 7-membered ring. In another exemplary embodiment, each R3a and Ra is a member independently selected from H, cyano, substituted or unsubstituted methyl, substituted or unsubstituted ethyl, trifluoromethyl, substituted or unsubstituted hydroxymethyl, substituted or unsubstituted hydroxyalkyl, substituted or unsubstituted benzyl. , substituted or unsubstituted phenyl, substituted or unsubstituted mechaptomethyl, substituted or unsubstituted mercaptoalkyl, substituted or unsubstituted aminomethyl, substituted or unsubstituted alkylaminomethyl, unsubstituted or substituted dialkylaminomethyl, unsubstituted or substituted arylaminomethyl, unsubstituted or substituted indolyl, and unsubstituted or substituted amido. In another exemplary embodiment, each R3a and R4a is a member independently selected from cyano, substituted or unsubstituted methyl, substituted or unsubstituted ethyl, trifluoromethyl, substituted or unsubstituted hydroxymethyl, substituted or unsubstituted hydroxyalkyl, substituted or unsubstituted benzyl, phenyl substituted or unsubstituted, substituted or unsubstituted mercaptomethyl, substituted or unsubstituted mercaptoalkyl, substituted or unsubstituted aminomethyl, substituted or unsubstituted alkylaminomethyl and substituted or unsubstituted alkylaminomethyl, substituted or unsubstituted arylaminomethyl, unsubstituted or substituted indolyl, substituted amido or not replaced In another exemplary embodiment, each R3a and R4a is a member selected from H, substituted or unsubstituted methyl, substituted or unsubstituted ethyl, substituted or unsubstituted propyl, substituted or unsubstituted isopropyl, substituted or unsubstituted butyl, substituted t-butyl. or unsubstituted, substituted or unsubstituted phenyl and substituted or unsubstituted benzyl. In another exemplary embodiment, R3a and R4a is a member selected from methyl, ethyl, propyl, isopropyl, butyl, t-butyl, phenyl and benzyl. In another exemplary embodiment, R3a is H and R4a is a member selected from methyl, ethyl, propyl, isopropyl, butyl, t-butyl, phenyl and benzyl. In another exemplary embodiment, R3a is H and R4a is H. In another exemplary embodiment, each R9a, R10a, Rlla and R12a is a member selected independently from H, OR *, NR * R **, SR *, -S (0 ) R *, -S (0) 2R *, -S (O) 2NR * R **, -C (C) R *, -C (0) 0R *, -C (0) NR * R **, halogen, cyano, nitro, substituted or unsubstituted methoxy, substituted or unsubstituted methyl, substituted or unsubstituted ethoxy, substituted or unsubstituted ethyl, trifluoromethyl, substituted or unsubstituted hydroxymethyl, substituted or unsubstituted hydroxyalkyl, substituted or unsubstituted benzyl, unsubstituted or substituted phenyl, unsubstituted or substituted phenyloxy, substituted or unsubstituted phenylmethoxy, substituted or unsubstituted thiophenyloxy, substituted or unsubstituted pyridinyloxy, substituted or unsubstituted pyrimidinyloxy, substituted or unsubstituted benzylfurano, substituted or unsubstituted methylthio, substituted mercaptomethyl or unsubstituted, substituted or unsubstituted mercaptoalkyl, substituted or unsubstituted phenylthio, thiophenylthio unsubstituted or substituted, unsubstituted or substituted phenylmethylthio substituted or unsubstituted pyridinylthio, substituted or unsubstituted pyrimidinylthio, unsubstituted or substituted benzylthiuram, unsubstituted or substituted phenylsulfonyl, unsubstituted or substituted benzylsulfonyl, substituted or unsubstituted phenylmethylsulfonyl, substituted thiophenylsulfonyl or unsubstituted, substituted or unsubstituted pyridinylsulfonyl, substituted or unsubstituted pyrimidinylsulfonyl, substituted or unsubstituted sulfonamidyl, substituted or unsubstituted phenylsulfinyl, substituted or unsubstituted benzylsulfinyl, unsubstituted or substituted phenylmethylsulphinyl, substituted or unsubstituted thiophenylsulfinyl, substituted or unsubstituted pyridinyl sulfinyl , substituted or unsubstituted pyrimidinylsulfinyl, substituted or unsubstituted amino, substituted or unsubstituted alkylamino, substituted or unsubstituted dialkylamino, substituted or unsubstituted trifluoromethylamino, substituted or unsubstituted aminomethyl, alkylamino unsubstituted or substituted laminomethyl, substituted or unsubstituted dialkylaminomethyl, unsubstituted or substituted arylaminomethyl, substituted or unsubstituted benzylamino, substituted or unsubstituted phenylamino, substituted or unsubstituted thiophenylamino, substituted or unsubstituted pyridinylamino, substituted or unsubstituted pyrimidinylamino, substituted indolyl or unsubstituted, substituted or unsubstituted morpholino, substituted or unsubstituted alkylamino, substituted or unsubstituted arylamido, substituted or unsubstituted ureido, substituted or unsubstituted carbamoyl and substituted or unsubstituted piperizinyl. In an exemplary embodiment, R9a, R10a, Rlla and R12a are selected from the foregoing list of substituents with the exception of -C (0) R *, -C (0) OR *, -C (0) NR * R **. In another exemplary embodiment, R9a, R10a, Rlla and R12a are members independently selected from fluoro, chloro, bromo, nitro, cyano, amino, methyl, hydroxylmethyl, trifluoromethyl, methoxy, trifluoromethoxy, ethyl, diethylcarbamoyl, pyridin-2-yl, pyridin. -3-yl, pyridin-4-yl, pyrimidinyl, piperazino, piperizinyl, piperizinocarbonyl, piperizinylcarbonyl, carboxyl, 1-tetrazolyl, 1-ethoxycarbonylmethoxy, carboxymethoxy, thiophenyl, 3- (butylcarbonyl) phenylmethoxy, lH-tetrazol-5-yl, 1-Ethoxycarbonylmethyloxy-, 1-ethoxycarbonylmethyl-, 1-ethoxycarbonyl-, carboxymethoxy-, thiophen-2-yl, thiophen-2-ylthio-, thiophen-3-yl, thiophen-3-ylthio, 4-fluorophenylthio, butylcarbonylphenylmethoxy, butylcarbonylphenylmethyl , butylcarbonylmethyl, 1- (piperidin-1-yl) carbonyl) methyl, 1- (piperidin-1-yl) carbonyl) methoxy, 1- (piperidin-2-yl) carbonyl) methoxy, 1- (piperidin-3-yl) ) carbonyl) methoxy, 1- (4- (pyrimidin-2-yl) piperazin-1-yl) carbonyl) methoxy, 1- (4- (pyrimidin-2-yl) piperazin-1-yl) carbonyl) methyl, - (4- (pyrimidin-2- il) piperazin-1-yl) carbonyl, 1-4- (pyrimidin-2-yl) piperazin-1-yl, 1- (4- (pyridin-2-yl) piperazin-1-yl) carbonyl), 1- (4- (pyridin-2-yl) piperazin-1-yl) carbonylmethyl, (1- (4- (pyridin-2-yl) piperazin-1-yl) carbonyl) -methoxy), 1- (4- (pyridine -2-yl) piperazin-1-yl, 1 H-indol-1-yl, morpholino-, morpholinyl, morpholinocarbonyl, morpholinylcarbonyl, phenylureido, phenylcarbamoyl, acetamide, 3- (phenylthio) -lH-indol-1-yl, 3- (2-cyanoethylthio) -lH-indol-1-yl, benzylamino, 5-methoxy-3- (phenylthio) -lH-indol-1-yl, 5-methoxy-3- (2-cyanoethylthio) -lH-indole 1-yl)), 5-chloro-lH-indol-1-yl, 5-chloro-3- (2-cyanoethylthio) -lH-indol-1-yl), dibenzylamino, benzylamino, 5-chloro-3- (phenylthio) -lH-indol-1-yl)), 4- (lH-tetrazol-5-yl) phenoxy, 4- (lH-tetrazol-5-yl) phenyl, 4- (lH-tetrazol-5-yl) ) phenylthio, 2-cyanophenoxy, 3-cyanophenoxy, 4-cyanophenoxy, 2-cyanophenylthio, 3-cyanophenylthio, 4-cyanophenylthio, 2-chlorophenoxy, 3-chlorophenoxy, 4-chlorophenoxy, 2-fluorophenoxy, 3-fluorophenoxy, 4-fluorophenoxy , 2-cyanobenzyl oxy, 3-cyanobenzyloxy, 4-cyanobenzyloxy, 2-chlorobenzyloxy, 3-chlorobenzyloxy, 4-chlorobenzyloxy, 2-fluorobenzyloxy, 3-fluorobenzyloxy, 4-fluorobenzyloxy, unsubstituted phenyl and unsubstituted benzyl. In an exemplary embodiment, the compound has a structure according to the following formula: In another exemplary embodiment, R9a, R10a, Rlla and R12a are members independently selected from H, halogen, cyano, nitro, substituted or unsubstituted methoxy, substituted or unsubstituted methyl, substituted or unsubstituted ethoxy, substituted or unsubstituted ethyl, trifluoromethyl , substituted or unsubstituted hydroxymethyl, substituted or unsubstituted hidroxialc¿uilo, substituted or unsubstituted benzyl, substituted or unsubstituted phenyl, substituted or unsubstituted phenyloxy, substituted or unsubstituted phenylmethoxy, tiofeniloxi substituted or unsubstituted, substituted or unsubstituted pyridinyloxy I pyrimidinyloxy substituted or unsubstituted, substituted bencilfurano or unsubstituted, substituted or unsubstituted methylthio, I mercaptomethyl substituted or unsubstituted, mercaptoalkyl substituted or unsubstituted, substituted or unsubstituted phenylthio, substituted or unsubstituted tiofeniltio, substituted phenylmethylthio or unsubstituted pyridinylthio substituted or unsubstituted, substituted or unsubstituted pyridinylthio ituido, substituted or unsubstituted benzylthiuramuranyl, substituted or unsubstituted phenylsulfonyl, substituted or unsubstituted benzylsulfonyl, unsubstituted or substituted phenylmethylsulfonyl, unsubstituted or substituted thiophenylsulfonyl, unsubstituted or substituted pyridinylsulfonyl, substituted or unsubstituted pyrimidinylsulfonyl, substituted or unsubstituted sulfonamidyl, phenylsulfinyl substituted or unsubstituted, substituted benzylsulfinyl or unsubstituted, substituted fenilmetilsulfinilo or unsubstituted, tiofenilsulfinilo substituted or unsubstituted pyridinylsulfonyl substituted or unsubstituted, pirimidinilsulfinilo substituted or unsubstituted, substituted or unsubstituted amino, alkylamino substituted or unsubstituted dialkylamino substituted or unsubstituted, substituted or unsubstituted trifluoromethylamino, substituted or unsubstituted aminomethyl, substituted or unsubstituted alkylaminomethyl, substituted or unsubstituted dialkylaminomethyl, substituted or unsubstituted arylaminomethyl, benzylam substituted ino or unsubstituted phenylamino substituted or unsubstituted, tiofenilamino substituted or unsubstituted, substituted pyridinylamino or unsubstituted, substituted pyrimidinylamino or unsubstituted indolyl substituted or unsubstituted morpholino substituted or unsubstituted alkylamido substituted or unsubstituted arylamido substituted or unsubstituted, substituted or unsubstituted ureido, substituted or unsubstituted carbamoyl and substituted or unsubstituted piperizinyl. In another exemplary embodiment, R9a, R10a, Rlla and R12a are members independently selected from H, fluoro, chloro, bromo, nitro, cyano, amino, methyl, hydroxylmethyl, trifluoromethyl, methoxy, trifluoromethoxy, ethyl, diethylcarbamoyl, pyridin-2-yl. pyridin-3-yl, pyridin-4-yl, pyrimidinyl, piperazino, piperizinyl, piperizinocarbonilo, piperizinilcarbonilo, carboxyl, 1-tetrazolyl, 1-ethoxycarbonylmethoxy, carboxymethoxy, thiophenyl, 3- (butylcarbonyl) phenylmethoxy, lH-tetrazol-5- yl, 1-etoxicarbonilmetiloxi-, 1-etoxicarbonilmetilo-, 1-etoxicarbonilo-, carboximetoxi-, thiophen-2-yl, thiophen-2-iltio-, thiophen-3-yl, thiophen-3-ylthio, 4-fluorophenylthio, butilcarbonilfenilmetoxi , butylcarbonylphenylmethyl, butylcarbonylmethyl, 1- (piperidin-1-yl) carbonyl) methyl, 1- (piperidin-1-yl) carbonyl) methoxy, 1- (piperidin-2-yl) carbonyl) methoxy, 1- (piperidin -3-yl) carbonyl) methoxy, 1- (4- (pyrimidin-2-yl) piperazin-1-yl) carbonyl) methoxy, 1- (4- (pyrimidin-2-yl) piperazin-1-yl) carbonyl ) methyl, 1- (4- (pi) rimidin-2-yl) piperazin-1-yl) carbonyl, 1-4- (pyrimidin-2-yl) piperazin-1-yl, 1- (4- (pyridin-2-yl) piperazin-1-yl) carbonyl ), 1- (4- (pyridin-2-yl) piperazin-1-yl) carbonylmethyl, (1- (4- (pyridin-2-yl) piperazin-1-yl) carbonyl) -methoxy), 1- ( 4- (pyridin-2-yl) piperazin-1-yl, 1H-indol-1-yl, morpholino-, morpholinyl, morpholinocarbonyl, morpholinylcarbonyl, phenylureido, phenylcarbamoyl, acetamide, 3- (phenylthio) -lH-indole-1- ilo, 3- (2-cyanoethylthio) -lH-indol-1-yl, benzylamino, 5-methoxy-3- (phenylthio) -lH-indol-1-yl, 5-methoxy-3- (2-cyanoethylthio) - lH-indol-1-yl)), 5-chloro-lH-indol-1-yl, 5-chloro-3- (2-cyanoethylthio) -lH-indol-1-yl), dibenzylamino, benzylamino, 5-chloro-3- (phenylthio) -lH -indol-1-yl)), 4- (lH-tetrazol-5-yl) phenoxy, 4- (lH-tetrazol-5-yl) phenyl, 4- (lH-tetrazol-5-yl) phenylthio, 2- cyanophenoxy, 3-cyanophenoxy, 4-cyanophenoxy, 2-cyanophenylthio, 3-cyanophenylthio, 4-cyanophenylthio, 2-chlorophenoxy, 3-chlorophenoxy, 4-chlorophenoxy, 2-fluorophenoxy, 3-fluorophenoxy, 4-fluorophenoxy, 2-cyanobenzyloxy, 3-cyanobenzyloxy, 4-cyanobenzyloxy, 2-chlorobenzyloxy, 3-chlorobenzyloxy, 4-chlorobenzyloxy. In an exemplary embodiment, R9a is H and R12a is H. In an exemplary embodiment, the compound has a combination of substituents for R9a, R10a, Rlla and R12a which is a member selected from those described in formulas (I), (the ), (Ib), (le), (Id), (le), (If), (ig), (Ih), (Ii), (Ij), (Ik), (II), (Im), (In), (lo), (Ip), Iq), (Go), (Is), (It), (Iu), (Iv), (Iw), (Iz), (iaa), (Lab), (Iac), (Iad), (Iae), (Iaf), (Iag), (Iah), (Iai), (Iaj), (Iak) above and / or the subsequent paragraphs that describe formulas (I), (a), (Ib), (le), (Id), (le), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (II), (Im), (In), (lo), (Ip), Iq), (Ir), (is), (It), (Iu), (Iv), (I), (Iz), (Iaa), (lab), (iac), dad), (Iae), (Iaf), (Iag), (Iah), (Iai), (Iaj), (Iak). In an exemplary embodiment, the portion of the cyclic boronic ester is as in the figure below is a member selected from a structure in Figures 12A-12I. In an exemplary embodiment, the compound has a structure according to the following formula: paic) In an exemplary embodiment, the compound has a structure according to the following formula: In an exemplary embodiment, the compound has a structure according to the following formula: (Xlle) In another exemplary embodiment, the compound has a structure that is a member selected from formulas (XII), (Xlla), (Xllb), (XIIc), (Xlld) and (Xlle) wherein L is a selected member of adenine substituted or unsubstituted, substituted or unsubstituted guanine, substituted or unsubstituted cytidine, substituted or unsubstituted uracil and substituted or unsubstituted thymine. In another exemplary embodiment, L is OH. In another exemplary embodiment, L is adenine. In another exemplary embodiment, the compound has a structure that is a member selected from In another exemplary embodiment, Al is a nucleic acid sequence of between 72 and 90 nucleotides. In another exemplary embodiment, Al is a nucleic acid sequence of between 35 and 150 nucleotides. In another exemplary embodiment, Al is a nucleic acid sequence of between 50 and 100 nucleotides. In another exemplary embodiment, Al is a nucleic acid sequence of between 75 and 85 nucleotides. In another exemplary embodiment, Al is a nucleic acid sequence which is a tRNA or a portion of a tRNA. In another exemplary embodiment, the tRNA or the tRNA portion is a member selected from alanyl tRNA, isoleucyl tRNA, leucyl tRNA, methionyl tRNA, lysyl tRNA, phenylalanyl tRNA, prolyl tRNA, threonyl tRNA and valil tRNA. In another exemplary embodiment, the tRNA or the tRNA portion is leucyl tRNA. In another exemplary embodiment, the tRNA or tRNA portion has a sequence that is a member selected from SEQ ID NOS: 18-62. In another exemplary embodiment, Al is a nucleic acid sequence in which two final nucleotides are each cytidine. In another exemplary embodiment, the compound further comprises a tRNA synthetase or a portion of a tRNA synthetase comprising the editing domain, wherein the compound is non-covalently linked to the editing domain of the tRNA synthetase. In another exemplary embodiment, the tRNA synthetase is a member selected from a mitochondrial tRNA synthetase and a cytoplasmic tRNA synthetase. In another exemplary embodiment, the tRNA synthetase is a member selected from alanyl tRNA synthetase, isoleucyl tRNA synthetase, leucyl tRNA synthetase, methionyl tRNA synthetase, lysyl tRNA synthetase, phenylalanyl tRNA synthetase, prolyl tRNA synthetase, threonyl tRNA synthetase and valyl tRNA synthetase. In an exemplary embodiment, the compound described herein is present in a microorganism described in this application. In another exemplary embodiment, there is a condition that the compound is not present in a microorganism that is a selected member of Saccharomyces cerevisiae, Aspergillus niger, Pseudomonas aeruginosa, Staphylococcus aureus, Aureobasidium pullulans, Fusarium solani, Penicillium pinophilum, Scopulariopsis brevicaulis, Streptoverticillium waksmanii, Al ternaria alternata, Cladosporium herbarum, Phoma violaceous, Stemphylium dentri ticum, Candida albicane, Escherichia coli and Glioclaeium roseum. In another exemplary embodiment, there is a condition that when the compound is present in a fungus, the fungus is not a selected member of Saccharomyces cerevisiae, Aspergillus niger, Fusarium solani, Penicillium pinophilum, Scopulariopsis brevicaulis, Streptoverticillium waksmanii, Al ternaría al ternata, Cladosporium herbarum, Phoma violaceous, Stemphylium dentri ticum, Candida albicans and Glioclasium roseum. In an exemplary embodiment, the compound is present in a microorganism that is a member selected from a dermatophyte, Trichophyton, Microsporum, Epidermophyton and yeast-like fungi. In an exemplary embodiment, there is a condition that when the compound is present in a yeast-type fungus, that yeast-type fungus is not a selected member of Aspergillus niger and Candida albicans. In another exemplary embodiment, the microorganism is a member selected from a dermatophyte, Trichophyton, Microeporum, Epidermophyton and yeast-like fungi. In an exemplary embodiment, the microorganism is a dermatophyte. In another exemplary embodiment, the microorganism is a selected member of Trichophyton species. In an exemplary embodiment, the microorganism is a selected member of T. rubrum and T. menagrophytee. In an exemplary embodiment, the microorganism is a dermatophyte and the dermatophyte is a selected member of T. rubrum and T. menagrophytee. In another exemplary embodiment, the compound is present in a human or an animal. In another exemplary embodiment, the compound is present in a microorganism that is on, or on the surface of, a human or an animal. In another exemplary embodiment, the compound is present in a microorganism that is present in a human nail unit of a human or a nail, hoof or horn component of an animal. In another exemplary embodiment, the compound is present in a microorganism that is present in a member selected from a human nail plate, human nail bed, proximal nail bending, lateral nail bending and combinations thereof. In another exemplary embodiment, the compound is present in a microorganism that is present in a member selected from a human nail plate and a human nail bed. In another exemplary embodiment, the compound is present in a microorganism that is present in a member selected from a proximal nail fold and a lateral nail fold. In another exemplary embodiment, the microorganism is a member selected from dermatophyte, Tri chophyton, My croeporum, Epi dermophyton and yeast-like fungi. In another exemplary embodiment, wherein the compound is a dermatophyte. In another exemplary embodiment, the dermatophyte is a selected member of T. rubrujn and T. menagrophytes.

I. f. Keratin Formulations When a compound of the invention described herein is applied to a nail component of a human, the compound absorbs or penetrates the nail. The human nail is composed mainly of keratin (ie, hair keratin or a-keratin) as well as residual amounts of lipid components. Therefore, in the process of treating a nail disease or killing or inhibiting the growth of a microorganism, a formulation comprising a "O human nail unit and a compound of the invention In another aspect, the invention provides a formulation comprising: (a) a compound that is a member selected from a compound containing boron, a compound containing 2'-amino ribofuranose, a compound that contains '5 3' -amino ribofuranose and combinations thereof and (b) a keratin-containing component which is a selected member of a human nail, skin and hair unit. In an exemplary embodiment, the compound of (a) makes contact with the component of (b). In an exemplary mode, the The component containing keratin is a nail plate of the human nail unit. In an exemplary embodiment, the keratin-containing component is a nail bed of the human nail unit. In an exemplary embodiment, the keratin-containing component is a proximal nail fold In the exemplary embodiment, the keratin-containing component is a lateral nail fold of the human nail unit In another exemplary embodiment, the human nail unit comprises a selected member of keratin and lipid. In another exemplary modalityKeratin is a selected member of dermal keratin and nail / hair keratin. In another embodiment, the lipid is a selected member of cholesterol sulfate, cerebroside, ceramide, free sterol, free fatty acids, triglycerides, ester esters, wax esters and squalene. In an exemplary embodiment, the compound is present in the formulation at a concentration that is a selected member of about 0.001%, about 0.01%, about 0.05%, about 0.1%, about 0.5%, about 15, about 1.5 %, approximately 2%, around 2.5%, approximately 3%. In another exemplary embodiment, keratin is present in the formulation at a concentration that is a selected member of about 99.99%, about 99.95%, about 99.90%, about 99.5%, about 99.0%, about 98.5%, around 98.0%, approximately 97.5% and around 97%. In another exemplary embodiment, the compound is a compound described herein. In another exemplary embodiment, the compound is as described in formulas (I), (a), (Ib), (le), (Id), (le), (If), (Ig), (Ih), (Ii), (ij), (ik), (II), (Im), (in), (lo), (Ip), Iq), (Ir), (Is), (It), (Iu) , (Iv), (Iw), (iz), daa), (Lab), (Iac), (lad), (iae), (laf), (Iag), (Iah), (Iai), (Iaj) ), (Iak), (II), (Ha), (Hb), (He), (Hd) and (III). In another exemplary embodiment, the compound is an acyclic boronic ester as described herein. In another exemplary embodiment, the compound is a member selected from C1-C96 described herein. In another exemplary embodiment, the compound is a member selected from a compound shown in Figures 19A-19K. In another exemplary embodiment, the compound is a member selected from a compound shown in Figures 20A-20H. In another exemplary embodiment, the compound is 1,3-dihydro-5-fluoro-1-hydroxy-2, 1-benzoxazole. In another exemplary embodiment, 1,3-dihydro-5-fluoro-l-hydroxy-2, 1-benzoxazole is present in the formulation at a concentration which is a selected member of about 0.001%, about 0.01%, about 0.05. %, approximately 0.1%, around 0.5%, approximately 1% and around 1.5%. In another aspect, the invention provides a method for forming this formulation, wherein the method comprises applying the compound to a formulation comprising keratin, thus forming the formulation. In an exemplary embodiment, the formulation comprising keratin is a human nail unit. In an exemplary embodiment, the keratin-comprising formulation is a member selected from a nail plate, nail bed, proximal nail fold and lateral nail fold. The methods for making these formulations are described in the examples section. I. g. ) Preparation of Edible Domain Inhibitors Containing Boron Compounds useful in the present invention can be prepared using commercially available starting materials, known intermediates or using the synthetic methods published in references described and incorporated by reference herein. I. h. ) Boronic Esters The following exemplary reaction schemes illustrate methods for preparing boron-containing molecules of the present invention. These methods are not limited to producing the compounds shown, but can be used to prepare a variety of molecules such as the compounds and complexes described herein. The compounds of the present invention can also be synthesized by methods not explicitly illustrated in the reaction schemes but are within the ability of one skilled in the art. The compounds can be prepared using readily available materials from known intermediates. In the following reaction lines, the symbol X represents bromine or iodine. The symbol Y is selected from H, lower alkyl and arylalkyl. The symbol Z is selected from H, alkyl and aryl. The PG symbol represents a protective group. The symbols A, D, E, G, Rx, R ?, Rz, Rla, R2a, R3a, Ra, R5a, R6a, R7a, R8a, R9a, R10a, Rlla and R12a can be used to refer to the corresponding symbols in the compounds described herein . Preparation Strategy of Boronic Acid # 1 In reaction scheme 1, steps 1 and 2, compounds 1 or 2 are converted to alcohol 3. In step 1, compound 1 is treated with a reducing agent in a suitable solvent . Suitable reducing agents include borane complexes, such as borane-tetrahydrofuran, borane-dimethylsulfide, combinations thereof and the like. Lithium aluminum hydride or sodium borohydride can also be used as reducing agents. The reducing agents can be used in amounts ranging from 0.5 to 5 equivalents, relative to compound 1 or 2. Suitable solvents include diethyl ether, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, combinations thereof and the like . The reaction temperatures vary from 0 ° C to the boiling point of the solvent used. The reaction completion times vary from 1 to 24 hours. In step 2, the carbonyl group of compound 2 is treated with a reducing agent in a suitable solvent. Suitable reducing agents include borane complexes, such as borane-tetrahydrofuran, borane-dimethylsulfide, combinations thereof and the like. Lithium aluminum hydride or sodium borohydride can also be used as reducing agents. The reducing agents can be used in amounts ranging from 0.5 to 5 equivalents, relative to compound 2. Suitable solvents include lower alcohol, such as methanol, ethanol and propanol, diethyl ether, tetrahydrofuran, 1,4-dioxane and 1,2 dimethoxyethane, combinations thereof and the like. The reaction temperatures vary from 0 ° C to the boiling point of the solvent used; Reaction completion times vary from 1 to 24 hours. In step 3, the hydroxyl group of compound 3 is protected with a protecting group which is stable under neutral or basic conditions. The protecting group is typically selected from methoxymethyl, ethoxyethyl, tetrahydropyran-2-yl, trimethylsilyl, tert-butyldimethylsilyl, tributylsilyl, combinations thereof and the like. In the case of methoxymethyl, compound 3 is treated with 1 to 3 equivalents of chloromethylmethyl ether in the presence of a base. Suitable bases include sodium hydride, potassium tert-butoxide, tertiary amines such as diisopropylethylamine, triethylamine, 1,8-diazabicyclo [5, 4, 0] undec-7-ene, and inorganic bases, such as sodium hydroxide, sodium carbonate, potassium hydroxide, potassium carbonate, combinations thereof and the like. The bases can be used in quantities that vary from 1 to 3 equivalents, in relation to compound 3. The 53 Reaction temperatures vary from 0 ° C to the boiling point of the solvent used; preferably between 0 and 40 ° C; Reaction completion times vary from 1 hour to 5 days. In the case of tetrahydropyran-2-yl, compound 3 is treated with 1 to 3 equivalents of 3,4-dihydro-2H-pyran in the presence of 1 to 10 mole% acid catalyst. Suitable acid catalysts include p-toluenesulfonic acid pyridinium, p-toluenesulfonic acid, camphor sulfonic acid, methanesulfonic acid, hydrogen chloride, sulfuric acid, combinations thereof and the like. Suitable solvents include dichloromethane, chloroform, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, toluene, benzene and acetonitrile, combinations thereof and the like. The reaction temperatures vary from 0 ° C to the boiling point of the solvent used; preferably between 0 and 60 ° C, and is completed in 1 hour to 5 days. In the case of trialkylsilyl, compound 3 is treated with 1 to 3 equivalents of chlorotrialkylsilane in the presence of 1 to 3 equivalents of base. Suitable bases include tertiary amines, such as imidazole, diisopropylethylamine, triethylamine, 1,8-diazabicyclo [5, 4, 0] undec-7-ene, combinations thereof and the like. The reaction temperatures vary from 0 ° C to the boiling point of the solvent used. Preferably between 0 and 40 ° C; the reaction completion times vary from 1 to 54 at 48 hours. In step 4, compound 4 is converted to boronic acid (5) through the halogen metal exchange reaction. Compound 4 is treated with 1 to 3 equivalents of an alkyl metal reactant relative to compound 4, such as n-butyl-lithium, sec-butyl-lithium, tert-butyl-lithium, isopropylmagnesium chloride or Mg-laps with or without an initiator such as diisobutylaluminum hydride (DiBAl), followed by the addition of 1 to 3 equivalents of trialkylborate relative to compound 4, such as trimethyl borate, triisopropyl borate or tributyl borate. Suitable solvents include tetrahydrofuran, ether, combinations thereof and the like. An alkyl metal reagent can also be added in the presence of trialkyl borate. The addition of butyl lithium is carried out between -100 and 0 ° C, preferably between -80 and -40 ° C. The addition of isopropylmagnesium chloride is carried out at -80 to 40 ° C, preferably at -20 to 30 ° C. The addition of Mg turns, with or without the addition of DiBAl, is carried out at -80 to 40 ° C, preferably at -35 to 3 ° C. The addition of trialkyl borate is carried out at -100 to 20 ° C. After the addition of trialkyl borate, the reaction is allowed to warm to room temperature, which is typically between -30 and 3 ° C. When the alkyl metal reagent is added in the presence of trialkyl borate, the reaction mixture is allowed to warm to room temperature after the addition. The reaction completion times vary from 1 to 12 hours. Compound 5 may not be isolated and may be used for the next step without purification or in a container. In step 5, the protecting group of compound 5 is stirred under acidic conditions to give the compound of the invention. Suitable acids include acetic acid, trifluoroacetic acid, hydrochloric acid, hydrobromic acid, sulfuric acid, p-toluenesulfonic acid and the like. The acids can be used in amounts ranging from 0.1 to 20 equivalents, relative to compound 5. When the protecting group is trialkylsilyl, basic reagents, such as tetrabutylammonium fluoride can also be used. Suitable solvents include tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, methanol, ethanol, propanol, acetonitrile, acetone, combination thereof and the like. The reaction temperatures vary from 0 ° C to the boiling point of the solvent used. Preferably between 10 ° C and the reflux temperature of the solvent. The reaction completion times vary from 0.5 to 48 hours. The product can be purified by methods known to those skilled in the art.

Reaction scheme 1 l or Il, R1 = H, W = (CR6R1) m, m = 0 In another aspect, the invention provides a method for making a boronic ester containing tetrahydropyran, the ester having a structure according to the following formula: wherein R1 and R2 are members independently selected from H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl. R1 and R2, together with the atoms to which they are attached, can optionally be joined to form a 4 to 7 membered ring. R9a, R10a, Rlla and R12a are members independently selected from H, OR *, NR * R **, SR *, -S (0) R *, -S (0) 2R *, -S (0) 2NR * R **, nitro, halogen, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl. R * and R ** is a member selected from H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl. The method comprises: a) subjecting a first compound to Grignard or organolithium conditions, the first composition has a structure according to the following formula: b) contacting the product of step a) with a borate ester, thereby forming the boronic ester containing tetrahydropyran. In an exemplary embodiment, halogen is a member selected from iodine and bromine. In another exemplary embodiment, the borate ester is a member selected from B (ORx) 2 (OR2), wherein R1 and R2 are each members independently selected from H, substituted or unsubstituted methyl, substituted or unsubstituted ethyl, propyl substituted or unsubstituted, substituted or unsubstituted isopropyl, substituted or unsubstituted butyl, substituted or unsubstituted t-butyl, substituted or unsubstituted phenyl and substituted or unsubstituted benzyl. R1 and R2, together with the atoms to which they are attached, can optionally form a member selected from substituted or unsubstituted dioxaborolane, substituted or unsubstituted dioxaborin, and substituted or unsubstituted dioxaborepane. In another exemplary embodiment, the borate ester is a member selected from B (OR1) 2 (OR2), wherein R1 and R2, together with the atoms to which they are attached, form a member selected from dioxaborolane, substituted or unsubstituted tetramethyldioxoborolane. , substituted or unsubstituted phenyldioxavorolane, dioxaborin, dimethyldioxaborin, and dioxaborepane. In another exemplary embodiment, the Grignard or organolithium conditions further comprise diisobutylaluminum hydride. In another exemplary embodiment, the temperature of the Grignard reaction does not exceed about 35 ° C. In another exemplary embodiment, the Grignard reaction temperature does not exceed about 40 ° C. In another exemplary embodiment, the temperature of the Grignard reaction does not exceed about 45 ° C. In an exemplary embodiment, step (b) is carried out at a temperature of about -30 ° C to about -20 ° C. In another exemplary embodiment, step (b) is carried out at a temperature of about -35 ° C to about -25 ° C. In another exemplary embodiment, step (b) is carried out at a temperature of about -50 ° C to about -0 ° C. In another exemplary embodiment, step (b) is carried out at a temperature of about -40 ° C to about -20 ° C. In another exemplary embodiment, the boronic ester containing tetrahydropyran is In another aspect, the invention provides a method for making a compound having a structure according to the following formula the method comprises: a) subjecting a first compound to Grignard or organolithium conditions, the first compound having a structure according to the following formula: b) rapidly quench the reaction with water and an organic acid, thereby forming the compound. In an exemplary embodiment, wherein the organic acid is a selected member of acetic acid. In another exemplary embodiment, the rapid cooling step essentially does not contact a strong acid. In another exemplary embodiment, the compound is 1,3-dihydro-5-fluoro-l-hydroxy-2, 1-benzoxazole. In another exemplary embodiment, the compound is purified by recrystallization from a recrystallization solvent, wherein the recrystallization solvent essentially does not contain acetonitrile. In an exemplary embodiment, the recrystallization solvent contains less than 2% acetonitrile. In an exemplary embodiment, the recrystallization solvent contains less than 1% acetonitrile. In an exemplary embodiment, the recrystallization solvent contains less than 0.5% acetonitrile. In an exemplary embodiment, the recrystallization solvent contains less than 0.1% acetonitrile. In an exemplary embodiment, the recrystallization solvent contains toluene and a hydrocarbon solvent. In an exemplary embodiment, the recrystallization solvent contains about 1: 1 of toluene: hydrocarbon solvent. In an exemplary embodiment, the recrystallization solvent contains about 2: 1 of toluene: hydrocarbon solvent. In an exemplary embodiment, the recrystallization solvent contains about 3: 1 of toluene: hydrocarbon solvent. In an exemplary embodiment, the recrystallization solvent contains about 4: 1 of toluene: hydrocarbon solvent. In an exemplary embodiment, the hydrocarbon solvent is a member selected from heptane, octane, hexane, pentane and nonane. In an exemplary embodiment, the recrystallization solvent is 3: 1 of toluene: heptane. Preparation Strategy of Boronic Acid # 2 In reaction scheme 2, step 6, compound 2 is converted to boronic acid (6) by means of a cross-coupling reaction catalyzed by transition metal. Compound 2 is treated with 1 to 3 equivalents of bis (pinacolato) diboron or 4,4,5,5-tetramethyl-1,3,2-dioxaborlane in the presence of transition metal catalyst, with the use of ligand and base suitable as needed. Suitable transition metal catalysts include palladium (II) acetate, palladium (II) acetoacetonate, tetrakis (triphenylphosphine) palladium, dichlorobis (triphenylphosphine) palladium, [1,1'-bis (diphenylphosphino) ferrocene] dichloropalladium (II) , combinations thereof and the like. The catalyst can be used in amounts ranging from 1 to 5 mol% relative to compound 2. Suitable ligands include triphenylphosphine, tri (o-tolyl) phosphine, tricyclohexylphosphine, combinations thereof and the like. The ligand can be used in amounts ranging from 1 to 5 equivalents relative to compound 2. Suitable bases include sodium carbonate, potassium carbonate, potassium phenoxide, triethylamine, combinations thereof and the like. The base can be used in amounts ranging from 1 to 5 equivalents relative to compound 2. Suitable solvents include N, N-dimethylformamide, dimethyl sulfoxide, tetrahydrofuran, 1,4-dioxane, toluene, combinations thereof and the like. The reaction temperatures vary from 20 ° C to the boiling point of the solvent used; preferably between 50 and 150 ° C; The reaction completion times vary from 1 to 72 hours. The pinacólico ester is then cut in oxidizing form to give compound 6. The pinacólico ester is treated with sodium periodate followed by acid. The sodium periodate can be used in amounts ranging from 0 to 5 equivalents relative to compound 6. Suitable solvents include tetrahydrofuran, 1,4-dioxane, acetonitrile, methanol, ethanol, combinations thereof and the like. Suitable acids include hydrochloric acid, hydrobromic acid, sulfuric acid and combinations thereof and the like. The reaction temperatures vary from 0 ° C to the boiling point of the solvent used; preferably between 0 and 50 ° C. The reaction completion times vary from 1 to 72 hours. In step 7, the carbonyl group of compound 6 is treated with a reducing agent in a suitable solvent to give a compound of the invention. Suitable reducing agents include borane complexes, such as borane-tetrahydrofuran, borane-dimethylsulfide, combinations thereof and the like. Lithium aluminum hydride or sodium borohydride can also be used as reducing agents. The reducing agents can be used in amounts ranging from 0.5 to 5 equivalents, relative to compound 6. Suitable solvents include lower alcohol, such as methanol, ethanol and propanol, diethyl ether, tetrahydrofuran, 1,4-dioxane and 1,2 dimethoxyethane, combinations thereof and the like. The reaction temperatures vary from 0 ° C to the boiling point of the solvent used. The reaction completion times vary from 1 to 24 hours.

Reaction scheme 2 OR1 i Stage 7 E'G ^ M * • II I, vlvw l or p, R '= H, W CR6R7) m. m = 0 Preparation Strategy of Boronic Acid # 3 In reaction scheme 3, step 8, the compounds of the invention can be prepared in a step of compound 3. Compound 3 is mixed with trialkyl borate and then treated with a metal reagent of alkyl. Suitable alkyl metal reagents include n-butyl lithium, eec-butyl lithium, tert-butyl lithium, combinations thereof and the like. Suitable trialkyl borates include trimethyl borate, triisopropyl borate, tributyl borate, combinations thereof and the like. The addition of butyl lithium is carried out between -100 and 0 ° C, preferably between -80 and -40 ° C. The reaction mixture is allowed to warm to room temperature after the addition. The reaction completion times vary from 1 to 12 hours. The trialkyl borate can be used in amounts ranging from 1 to 5 equivalents relative to the compound 3. The alkyl metal reagent can be used in amounts ranging from 1 to 2 equivalents relative to the compound 3. Suitable solvents include tetrahydrofuran, ether, 1,4-dioxane, 1,2-dimethoxyethane, toluene, hexanes, combinations thereof and the like. The reaction completion times vary from 1 to 12 hours. Alternatively, a mixture of compound 3 and trialkyl borate can be brought to reflux for 1 to 3 hours and the alcohol molecule that is formed after the ester bond can be distilled before the addition of the alkyl metal reagent. Reaction scheme 3 Preparation Strategy of Boronic Acid # 4 In reaction scheme 4, step 10, the methyl group of compound 7 is brominated using N-bromosuccinimide.

The N-bromosuccinimide may be used in amounts ranging from 0.9 to 1.2 equivalents relative to compound 7. Suitable solvents include carbon tetrachloride, tetrahydrofuran, 1,4-dioxane, chlorobenzene, combinations thereof, and the like. The reaction temperatures vary from 20 ° C to the boiling point of the solvent used; preferably between 50 and 150 ° C; the completion times of the reaction vary from 1 to 12 hours. In step 11, the bromomethylene group of compound 8 is converted to benzyl alcohol 3. Compound 8 is treated with sodium acetate or potassium acetate. These acetates can be used in amounts ranging from 1 to 10 equivalents relative to compound 8. Suitable solvents include tetrahydrofuran, 1,4-dioxane, N, N-dimethylformamide, N, N-dimethylacetamide, N-methylpyrrolidone, dimethyl sulfoxide. , combinations thereof and the like. The reaction temperatures vary from 20 ° C to the boiling point of the solvent used; preferably between 50 and 100 ° C; the completion times of the reaction vary from 1 to 12 hours. The resulting acetate is hydrolyzed to compound 3 under basic conditions. Suitable bases include sodium hydroxide, lithium hydroxide, potassium hydroxide, combinations thereof and the like. The base can be used in amounts ranging from 1 to 5 equivalents relative to compound 8. Suitable solvents include methanol, ethanol, tetrahydrofuran, water, combinations thereof and the like. The reaction temperatures vary from 20 ° C to the boiling point of the solvent used; preferably between 50 and 100 ° C; the completion times of the reaction vary from 1 to 12 hours. Alternatively, compound 8 can be converted directly to compound 3 under the similar condition above.

Steps 3 to 5 convert compound 3 to a compound of the invention. Reaction scheme 4 E'G? X Stage 10_ E "* ^ * 8 I or II, R '= H, W = (CR6R7) m, m = 0 Preparation Strategy of Boronic Acid # 5 In reaction scheme 5, step 12, compound 2 is treated with (methoxymethyl) triphenylphosphonium chloride or (methoxymethyl) triphenylphosphonium bromide in the presence of a base followed by hydrolysis with acid to give the compound 9. Suitable bases include sodium hydride, potassium tert-butoxide, lithium diisopropylamide, butyllithium, lithium hexamethyldisilazane, combinations thereof and the like. The salt (methoxymethyl) triphenyphosphonium can be used in amounts ranging from 1 to 5 equivalents relative to compound 2. The base can be used in amounts ranging from 1 to 5 equivalents relative to compound 2. Suitable solvents include tetrahydrofuran, , 2-dimethoxyethane, 1,4-dioxane, ether, toluene, hexane, N, N-dimethylformamide, combinations thereof and the like. Reaction temperatures vary from 0 ° C to the boiling point of solvent used; preferably between 0 and 30 ° C; the completion times of the reaction vary from 1 to 12 hours. The enolic ether formed is hydrolyzed under acidic conditions. Suitable acids include hydrochloric acid, hydrobromic acid, sulfuric acid and the like. Suitable solvents include tetrahydrofuran, 1,2-dimethoxyethane, 1,4-dioxane, methanol, ethanol, combinations thereof and the like. The reaction temperatures vary from 20 ° C to the boiling point of the solvent used; preferably between 50 and 100 ° C; the completion times of the reaction vary from 1 to 12 hours. Steps 2 to 5 convert compound 9 to a compound of the invention. Reaction scheme 5 H, R '= H Strategy of Preparation of Boronic Acid # 6 In reaction scheme 6, the compound (I) wherein R1 is H is converted to compound (I) wherein R1 is alkyl when mixed with alcohol corresponding, R1OH. Suitable solvents include tetrahydrofuran, 1,2-dimethoxyethane, 1,4-dioxane, toluene, combinations thereof, and the like. Alcohol (R1OH) can be used as the solvent as well. The reaction temperatures vary from 20 ° C to the boiling point of the solvent used; preferably between 50 and 100 ° C; the completion times of the reaction vary from 1 to 12 hours. Reaction scheme 6 l or II, R '= H l or p. Rl? H Preparation Strategy of Boronic Acid # 7 In the reaction scheme 7, the compound (Ia) is converted to its complex with aminoalcohol (Ib). The compound is treated with HORxNRlaRlb. The aminoalcohol can be used in amounts ranging from 1 to 10 equivalents relative to the compound (la). Suitable solvents include methanol, ethanol, propanol, tetrahydrofuran, acetone, acetonitrile, 1,2-dimethoxyethane, 1,4-dioxane, toluene, N, N-dimethylformamide, water, combinations thereof, and the like. The reaction temperatures vary from 2 ° C to the boiling point of the solvent used; preferably between 50 and 100 ° C; the completion times of the reaction vary from 1 to 24 hours.

Reaction scheme 7 o Ha Ib or Hb The compounds of the invention can be converted into hydrates and solvates by methods similar to those described above. I. h. ) Borinic Esters The methods for making borinic esters are well known in the art, and it is within the knowledge of one skilled in the art to use these methods to be able to make the boronic esters described herein. Examples include the US patent. No. 10 / 868,268 and provisional patent of E.U.A. No. (Case No. 64507-5021PR, filed May 2, 2006) which are incorporated herein by reference. I. i. ) 2'-amino or 3 '-amino ribo furanoses The methods for making 2'-aminoribofuranoses or 3'-aminoribofuranoses are known in the art, and it is within the knowledge of one skilled in the art to use these methods to make the '-aminorrifuranosas described here. Ashton et al. (Canadian patent application 2,031,644 (1991)) and Durette, et al. (UK patent application 2,207,678 (1989)) describe the synthesis of the amino acid starting material for compound D5. Hardee, et al. , (PCT Int. Application WO2005020885 (2005)) describes the synthesis of the nucleoside starting material for compound D6. Sakthivel, (Sakthivel, et al., Tet., 46 (22): 3383-3887 (2005)) Sartorelli, et al. , (publication of patent application of E.U.A. 2004116362); Roberts, et al. , (PCT Int. application WO2003093290); Liu, et al. , Nucleosides, Nucleotides & Nucleic Acide, 20 (12): 1975-2000 (2001); Minakawa, et al. , J. Org. Chem., 64 (19): 7158-7172 (1999); Daelemans, et al. , Molecular Pharmacology, 52 (6): 1157-1163 (1997) describe all syntheses of the nucleoside starting material for compound D7. Examples of how to prepare these compounds are shown below: Compounds 1-14 are produced by a final step (Lincecum, TL et al., S. Molecular Cell, 11: 951-963 (2003); Kim, B.-T. et al., J. Bull. Korean Chem Soc, 25: 243-248 (2004)): Compounds 15-18 are produced by a final step (see Lincecum): Methods for preparing dimers, trimers and higher homologs of small organic molecules, such as those for use in the present invention, as well as methods for functionalizing a molecule of polyfunctional structure are well known to those skilled in the art. For example, an aromatic amine of the invention is converted to the corresponding isothiocyanate by the action of thiophosgene. The resulting isothiocyanate is coupled to an amine of the invention, thus forming either a homo- or heterodimeric species. Alternatively, the isothiocyanate is coupled with an amine-containing base structure, such as polylysine, thereby forming a conjugate between a polyvalent framework and a compound of the invention. If it is desired to prepare a polyvalent heterofunctionalized species, the polylysine is submerged with the first isothiocyanate and subsequently labeled with one or more different isothiocyanates. Alternatively, a mixture of isothiocyanates is added to the base structure. The purification proceeds by, for example, size exclusion chromatography, dialysis, nanofiltration or the like. II. Assays for TnD Synthetase Editing Domain Inhibitors Recognized gene and molecular biology techniques are useful for identifying compounds that bind to and / or inhibit the editing domain of a tRNA synthetase. In addition, these techniques are useful to distinguish whether a compound binds to and / or inhibits the synthetic domain, the editing domain, or both the editing and synthetic domain. In an exemplary assay, the activity of a representative compound against the editing domain was confirmed. To identify the target of the antimycotic compound containing new boron CIO, mutants in S. cerevieiae showing resistance to the compound CIO were isolated. The characterization of 11 mutants showed that they have an 8-64 fold improvement in CIO resistance over the wild type. The mutants also showed to be sensitive to several antifungal agents with known modes of action, suggesting that the cellular objective of CIO is different from the objective of the other antifungal agents. Isolation of the three different plasmids carrying CDC60 from plasmid libraries generated from the three independently isolated mutants involved CDC60, the gene for cytoplasmic leucyl-tRNA synthetase in resistance against CIO. Sequence analysis of CDC60 of the 11 mutants revealed that the mutations were all located in the editing domain of this enzyme. In a series of additional experiments, additional copies of the CDC60 gene were introduced into S. cerevisiae, which gave rise to an eight-fold improvement in CIO resistance. These findings confirm a strong link between the activity of editing the enzyme and the inhibition of IOC, which implies a new mechanism of tRNA synthetase inhibition. Assays to determine if, and how effectively, a particular compound binds to and / or inhibits the editing domain of a selected tRNA synthetase are also shown in this; and additional assays are readily available to those of skill in the art. Briefly, in an exemplary assay, an inappropriately loaded tRNA and a tRNA synthetase that is able to avoid inappropriately loaded tRNA are combined. The resulting mixture is contacted with the putative inhibitor and the degree of editing inhibition is observed. Another trial uses genetics to show that a drug works through the editing domain. In this assay, the compound is first tested against a strain of cells that overexpress copies of the tRNA synthetase gene. The effect of the compound on the overexpression strain is compared to a control strain to determine whether the compound is active against the synthetase. If the minimum inhibitory concentration (MIC) is 2 times higher in the strain with additional copies of the synthetase gene than the MIC of the inhibitor against a wild-type cell, an additional genetic screen is carried out to determine if the increased resistance is due to mutations in the editing domain. In this second screen, the control strain is confronted against a high concentration of the inhibitor. The colonies that survive the attack are isolated and the DNA of these cells is isolated. The editing domain is amplified using a readable PCR enzyme and the appropriate primers. The PCR product can be purified using standard procedures. The mutant DNA amplified in sequence is compared to wild type. If the mutant DNA carries mutations in the editing domain, these results would suggest that the compound binds to the editing domain and affects the editing function of the molecule through this domain. The assays shown above are useful essentially in any microbial system, eg, bacterial, fungal, parasitic, viral and the like. Generally, the compounds to be tested are present in the assays in amounts ranging from about 1 pM to about 100 mM, preferably about 1 pM to about 1 uM. Other compounds vary from about 1 nM to about 100 nM, preferably about 1 nM to about 1 uM. The effects of the test compounds on the function of the enzymes can also be measured by any suitable physiological change. When functional consequences are determined using intact cells or animals, a variety of effects can also be added such as release of transmitters, release of hormones, transcriptional changes to both known and uncharacterized genetic markers, changes in cellular metabolism such as cell growth and pH changes and changes in intracellular second messengers such as Ca2 + or cyclic nucleotides. High emission screening (HTS) is also useful for identifying candidate candidates for the invention. Using the assays shown herein and others readily available in the art, those skilled in the art will be able to readily and routinely determine other compounds and classes of compounds that operate to bind to and / or inhibit the editing domain of tRNA synthetases. . In another aspect, the invention provides a method for identifying a compound that binds to an editing domain of a tRNA synthetase, comprising: a) contacting the editing domain with a test compound under conditions suitable for binding and b ) detect the binding of the test compound to the editing domain. In an exemplary embodiment, detecting the binding of the compound comprises using at least one detectable element, isotope or chemical label attached to the compound. In an exemplary embodiment, the element, isotope or chemical marker is detected by a fluorescent, luminescent, radioactive or absorbance reading. In an exemplary embodiment, contacting the test compound with the editing domain also includes contacting the test compound and the editing domain with a selected member of AMP and a molecule with a terminal adenosine. In an exemplary mode, the tRNA synthetase is derived from a member selected from alanyl tRNA, isoleucyl tRNA, leucyl tRNA, methionyl tRNA, lysyl tRNA, phenylalanyl tRNA, prolyl tRNA, threonyl tRNA and valil tRNA. In an exemplary embodiment, the tRNA synthetase is derived from leucyl tRNA synthetase. In an exemplary embodiment, the tRNA synthetase is derived from a mutated tRNA synthetase, wherein the mutated tRNA synthetase comprises amino acid mutations in an editing domain. In another exemplary embodiment, the mutated tRNA synthetase comprises amino acid mutations in the editing domain as listed in Table 4. In another exemplary embodiment, wherein the editing domain of a tRNA synthetase comprises the amino acid sequence of SEQ ID NOS: 1-15. In another aspect, the invention provides a method for identifying a compound that binds to a tRNA synthetase editing domain, the assay comprises: a) contacting the editing domain of a tRNA synthetase with the compound under suitable conditions for the binding of the compound to the editing domain of a tRNA synthetase; b) comparing a biological activity of the editing domain of a tRNA synthetase that makes contact with the compound with biological activity when no contact is made with the compound and c) identifying the compound as binding to the editing domain of a tRNA synthetase if the activity The biological domain of the editing of a tRNA synthetase is reduced when it makes contact with the compound. In an exemplary embodiment, the biological activity is non-cognate amino acid hydrolysis. In another exemplary embodiment, the hydrolysis of the non-cognate amino acid is detected through the use or more markers. In another exemplary embodiment, the labels include a radioactive label, a fluorescent label, an antibody or a combination thereof. In another exemplary embodiment, markers can be detected using spectroscopy. In another exemplary embodiment, the editing domain of a tRNA synthetase is derived from a member selected from alanyl tRNA, isoleucyl tRNA, leucyl tRNA, methionyl tRNA, lysyl tRNA, phenylalanyl tRNA, prolyl tRNA, threonyl tRNA and valil tRNA. In another exemplary embodiment, the editing domain of a tRNA synthetase is derived from leucyl tRNA synthetase. In another aspect, the invention provides a method for generating tRNA molecules with a non-cognate amino acid, comprising: a) creating or isolating a mutated tRNA synthetase with altered amino acid editing domains and b) contacting a tRNA molecule with the Mutated tRNA synthetase and a non-cognate amino acid. In another exemplary embodiment, the mutated tRNA synthetase contains one or more amino acid mutations in an editing domain. In another exemplary embodiment, the mutated tRNA synthetase is incapable of binding to 1,3-dihydro-5-fluoro-l-hydroxy-2, 1-benzoxazole. In another exemplary embodiment, the mutated tRNA synthetase is capable of binding to 1,3-dihydro-5-fluoro-l-hydroxy-2, 1-benzoxazole. In another aspect, the invention provides a composition comprising one or more tRNA molecules linked to 160 non-cognate amino acids, wherein the tRNA molecules are synthesized using one or more mutated tRNA synthetases isolated to a microorganism or a cell line derived from a microorganism. In an exemplary embodiment, the microorganism is a fungus or a yeast. In an exemplary embodiment, the mutated tRNA synthetases contain amino acid mutations in their editing domains. In an exemplary embodiment, the mutated tRNA synthetases comprise point mutations in the editing domain as listed in Table 4. III. Sequences of amino acids and nucleotides used in assays TRNA sequences that interact with the tRNA synthetase-ClO-AMP complex Transfer RNA molecules (tRNAs) translate mRNA into a protein on a ribosome. Each transfer RNA contains an anti-codon region that hybridizes with mRNA, and an amino acid that can be linked to the growing peptide. The structural gene of tRNA is approximately 72 to 90 nucleotides long and is doubled in a trefoil leaf structure (Sharp SJ, Schaack J., Coolen L., Burke DJ and Soli D., "Structure and Transcription of eukaryotic tRNA genes. ", Crit. Rev. Biochem, 19: 107-144 (1985), Geiduschek EO, and Tocchini-Valentini," Transcription by RNA Polymerase III ", Annu Rev. Biochem. 57: 873-914 (1988)). In one embodiment, CIO makes contact with AMP and a tRNA synthetase, and the tRNA synthetase in turn makes contact with a tRNA molecule. In another embodiment, CIO makes contact with AMP of the tRNA molecules and a tRNA synthetase. The nucleotide sequence of the tRNA molecule can be determined by the identity of the tRNA synthetase involved. For example, for leucyl tRNA synthetase, the bound tethered tRNA molecule will be tRNA-leucine (SEQ ID NO: 3), but a non-cognate tRNA, such as isoleucine, (SEQ ID NO: 4) may be linked under certain conditions. In these and other embodiments, the term "non-cognate" is intended to encompass both the singular and plural forms of the word, ie, the phrase "non-cognate amino acid" comprises one or more amino acids. SEQ ID NO: 3 corresponds to the nucleotide sequence of the tRNA-Leu gene of Saccharomycee cerevisiae: gggagtttgg ccgagtggtt taaggcgtca gatttaggct ctgatatctt cggatgcaagggttcgaatc ccttagctct cacea SEQ ID NO: 4 corresponds to the nucleotide sequence of the tRNA-Ile gene of Saccharomyces cerevieiae: gaaactataa ttcaattggt tagaatagta tttgataag gtacaaatat aggttcaatc cctgttagtt teateca Polypeptides used in binding and inhibition eneayoe In some binding and inhibition assays, it is more effective to use a portion of a tRNA synthetase molecule instead of the whole protein itself. In these assays, tRNA synthetase-derived polypeptides are used in the experiment. In a preferred embodiment, polypeptide fragments corresponding to the editing domain of a tRNA synthetase molecule are used in binding assay experiments. Two of these fragments are represented by SEQ ID NO: 1 and SEQ ID NO: 2. SEQ ID NO 1: TPQEYIGVKIEALEFADDAAKIIDSSSDLDKSKKFYFVAATLRPETMYGQTCCFVSPTIEYG IFDAGDSYFITTERAFKNMSYQKLTPKRGFYKPIVTVPGKAFIGTKIHAPQSVYPELRILPM ETVIATKGTGWTCVPSNSPDDYIITTKDLLHKPEYYGIKPE IDHEIVPIMHTEKYGDLTA KAIVEEKKIQSPKDKNLLAEAKKIAYKEDYYTGTMIYGPYKGEKVEQAKNKVKADMIAAGEA FVYNEPESQDP SEQ ID NO 2: MTPQEYIGVKIEALEFADDAAKIIDSSSDLDKSKKFYFVAATLRPETMYGQTCCFVSPTIEY GIFDAGDSYFITTERAFKNMSYQKLTPKRGFYKPIVTVPGKAFIGTKIHAPQSVYPELRILP METVIATKGTGWTCVPSNSPDDYITTKDLLHKPEYYCIKPEWIDHEIVPIMHTEKYGDLTA KAIVEEKKIQSPKDKNLLAEAKKIAYKEDYYTGTMIYGPYKGEKVEQAKNK? KADMIAAGEA FVYNEPESQDPQDPNSSSVDKLAAALEHHHHH IV. Methods to inhibit the editing domain of TRNA synthetase According to another aspect of the invention, a method for joining and / or inhibiting the editing domain of a TRNA synthetase is provided, which comprises contacting a tRNA synthetase with a compound that inhibits the editing domain under the conditions in which the tRNA synthetase interacts with its substrate to form an amino acyl adenylate intermediate and, preferably, to form a charged tRNA. These conditions are known to those skilled in the art. In an exemplary embodiment, the compound is one described herein. The tRNA synthetase is contacted with a sufficient amount of inhibitor to result in a detectable amount of tRNA synthetase inhibition. This method can be carried out in a tRNA synthetase that is contained within an organism or which is outside an organism. In an exemplary embodiment, the method is carried out on a tRNA synthetase that is contained within a microorganism or a microbial cell that is on, or on the surface of, a human or an animal. The method results in a reduction in the amount of charged tRNA produced by the tRNA synthetase which has an inhibited editing domain. In an exemplary embodiment, the inhibition takes place in a cell, such as a microbial cell. In another exemplary embodiment, the microbial cell is a bacterium, fungus, yeast or parasite. In another exemplary embodiment, the tRNA synthetase is a mitochondrial tRNA synthetase or a cytoplasmic tRNA synthetase. In an exemplary embodiment, the invention provides a method for inhibiting the conversion of a tRNA molecule to a charged tRNA molecule. The method includes contacting a tRNA synthetase with a compound effective to inhibit the activity of an editing domain of the tRNA synthetase, under conditions sufficient to inhibit activity, thereby inhibiting the conversion where the compound is a member selected from those compounds described herein. In an exemplary embodiment, the compound is a member selected from a cyclic boronic ester, cyclic borinic ester, 2'-amino ribofuranose portion and a 3'-amino ribofuranose portion. In an exemplary embodiment, the inhibition occurs within a cell, and the cell is a microbial cell. In another exemplary embodiment, the microbial cell is a member selected from a bacterium, fungus, yeast and parasite. In an exemplary embodiment, the tRNA synthetase is a member selected from a mitochondrial tRNA synthetase and a cytoplasmic tRNA synthetase. In another exemplary embodiment, the tRNA synthetase is a member selected from alanyl tRNA, isoleucyl tRNA, leucyl tRNA, methionyl tRNA, lysyl tRNA, phenylalanyl tRNA, prolyl tRNA, threonyl tRNA and valil tRNA. In another exemplary embodiment, the compound has a KD, synthesis of more than 100 μM against a synthetic domain of the tRNA synthetase. In certain embodiments, the mechanism of action of the compound is to inhibit the conversion of a tRNA molecule to a charged tRNA molecule by binding to and / or inhibiting at least one synthetase editing domain. Compounds for use in this method can also inhibit or otherwise interact with the synthetic domain (e.g., the active site of the synthetic domain). In a currently preferred embodiment, the editing domain is selectively inhibited in the presence of the synthetic domain. In a preferred embodiment, the synthetic domain is essentially uninhibited, while the editing domain is inhibited by at least 50%, preferably at least 60%, most preferably at least 70%, at least more preferably at least 80% and still more preferably at least 90% of the activity of the tRNA synthetase. In another preferred embodiment, the synthetic domain is inhibited at most in 50%, preferably at most 30%, preferably at most 20%, 10%, preferably at most 8%, most preferably at most 5%, even more preferably when much 3% and still more preferably when much 1%. The inhibition of the editing domain produces a reduction in the amount of the appropriately charged tRNA that results in the retardation or arrest of cell growth and division. In another exemplary embodiment, the ratio of a minimum concentration of the compound that inhibits the editing domain to a minimum concentration of the compound that inhibits the synthetic domain of the tRNA synthetase, represented as KD, edition / D, synthesis, is less than one. In another exemplary embodiment, the KD, Test / KD, synthesis of the compound is a selected member of less than 0.5, less than 0.1 and less than 0.05. V. Methods for Inhibiting the Growth of Microorganisms or Killing Microorganisms In a further aspect, the invention provides a method for inhibiting the growth, or killing, of a microorganism, preferably a bacterium, fungus, virus, yeast or parasite, comprising in contact the microorganism with an inhibitor of a tRNA synthetase, for example, a compound described by a formula listed herein, under conditions that allow the entry of the compound into the body. In a further aspect, the invention provides a method for inhibiting the growth, or killing, a microorganism, preferably a bacterium, fungus, virus, yeast or parasite, comprising contacting the microorganism with a compound that is a member selected from the formulas (I), (la), (Ib), (le), (Id), (le), (If), (Ig), (Ih), (Ii), (Ij), (Ik), (II), (Im), (In), (lo), (Ip), (Iq), (Ir), (Is), (It), (Iu), (Iv), (I), (Ix) ), (Iy), (Iz), (Iaa), (Lab), (iac), (lad), (Iae), (Iaf), (Iag), (Iah), (Iai), (Iaj), (iak), (II), (lia), (Iib), (lie), (lid), (III), (VIII), (Villa), (VlIIb), (VIIIc), (VHId), (VUIe ), (IX), for example, a compound described by a formula listed herein, under conditions that allow the entry of the compound into the organism. In a further aspect, the invention provides a method for inhibiting the growth, or killing, a microorganism, preferably a bacterium, fungus, virus, yeast or parasite, comprising contacting the microorganism with a compound that is described either in Figures 19A-19K or Figures 20A-20H, for example, a compound described by a formula listed herein, under conditions that allow entry of the compound into the microorganism. In an exemplary embodiment, the compound inhibits tRNA synthetase through the editing domain of the synthetase. These conditions are known to a person skilled in the art and the specific conditions are shown in the examples appended hereto. This method includes contacting a microbial cell with a therapeutically effective amount of an editing domain inhibitor to inhibit tRNA synthetase in vivo or in vi tro. In another aspect, the invention provides a method for inhibiting the growth of a microorganism, or killing a microorganism, or both, comprising contacting the microorganism with a compound described herein. The microorganisms are selected members of fungi, yeasts, viruses, bacteria and parasites. In another exemplary embodiment, the microorganism is inside, or on the surface of an animal. In an exemplary embodiment, the animal is a selected member of human, cattle, deer, reindeer, goat, sheep, pig, sheep, horse, cow, bull, dog, guinea pig, gerbil, rabbit, cat, camel, yack , elephant, ostrich, otter, chicken, duck, goose, hen 1 of Guinea, pigeon, swan and turkey. In another modality, the animal is a human. In an exemplary embodiment, the microorganism is a selected member of a fungus and a yeast. In another exemplary embodiment, the fungus or yeast is a member selected from Candida species, species of Trichophyton, species of My roeporium, species of Aspergillus, species of Cryptococcus, species of Blastamyces, species of Cocciodiodes, species of Histoplasma, species of Paracoccidiodee , Phycamycetee species, Malaeeezia species, Fuearium species, Epidermophyton species, Schytalidium species, Scopulariqpsis species, Alternarla species, Penicillium species, Phalophora species, Fhizcpue species, Scedosporium species and Zygcmycetes class. In another exemplary embodiment, the fungus or yeast is a member selected from Aspergillus fumigatus (A. fumigatus), Blastapyces dermatitidie, Candida Albicans (C. albicans, both strains sensitive and resistant to fluconazole), Candida glabrata (C. glabrata), Candida krueei (C. krueei), Cryptococcus neoformans (C. neoformans), Candida parapeyloeum (C. parapeiloeis), Candida trqpicalis (C. tropicalie), Cocciodiodes immitis, Epidermophyton floccoeum (E. floccoeum), Fuearium solani (F. solani), Hietoplasma capeulatum, Malaesezia fúrfur (M. fúrfur), Malaeeezia pachydermatie (M. pachydermatis), Malaeeezia eympodialie (M. eympodialie), Microeporum audouinii (M. audouinii), Microsporum canis (M. canie), Microeporum gypeeum (M. gypseum) , Paracoccidiodee braeiliensie and Phycc ycetes spp, Trichophyton mentagrophytes (T. mentagrophyt-ee), Trichophyton rubrum (T. rubrum), Trichophyton tonsurans (T. tonsurans). In another exemplary embodiment, the fungus or yeast is a member selected from Trichophyton concentricum, T. violaceum, T. echcenleinii, T. verrucoeum, T. eoudanenee, Microeporum gypeeum, M. equinum, Candida guilliermondii, Malaeeezia globosa, M. obtuee, M. restricted, M. elooffiae and Aepergillus flavue. In another exemplary embodiment, the fungus or yeast is a selected member of dermatophytes, Trichophyton, Microeporum, Epidermophyton and yeast-like fungi. In an example modality, the microorganism is a bacterium. In one example, the bacterium is a gram-positive bacterium. In another exemplary embodiment, the gram-positive bacterium is a member selected from Staphylococcus species, Streptococcus species, Bacillue species, Mycobacterium species, Corynebacterium species (species of Propionibacterium), Clostridium species, Actinomyces species, species of Enterococcus and Streptomyces species. In another example, the bacterium is a gram-negative bacterium. In another embodiment, the gram-negative bacterium is a member selected from Acinetobacter species, Neiseeira species, Peeudomonae species, Brucilla species, Agrobacterium species, Bordetella species, Eecherichia species, Shigelia species, Yereinia, species of Salmonella, species of Klebeiella, species of En erobac er, species of Haemophilue, species of Paeteurella, species of Streptobacillue, species of spirochetes, species of Campylobacter, species of Vibrio and species of Helicobacter species. In another exemplary embodiment, the bacterium is a selected member of Propionibacterium acnee; Staphylococcus aureue; Staphylococcus epidermidis, Staphylococcus eaprophyticue; Streptococcus pyogenee; Streptococcal agalactiae; Streptococcus pneumoniae; Enterococcus faecalis; Enterococcus faecium; Bacillus anthracis; Mycobacterium avium-intracellulare; Mycobacterium tuberculoeie, Acinetobacter baumanii; Corynebacterium diphtheria; Clostridium perfringens; Clostridium botulinum; Cloetridium tetani; Clostridium difficile; Neisseria gonorrhoeae; Neisseria meningi tidis; Peeudomonae aeruginoea; Legionella pneumophila; Eecherichia coli; Yereinia peetis; Hemophilus influenzae; Helicobacter pylori; Campylobacter fetoe; Campylobacter jejuni; Vibrio cholerae; Vibrio parahemolyticue; Trepomena palli-dum; Israeli Actinomyces; Rickettsia prowazekii; Ricketteia ricketteii; Chlamydia trachomatis; Chlamydia pei ttaci; Brucilla abortue; Agrobacterium tumefaciene and Francieella tulareneie. In an exemplary embodiment, the microorganism is a bacterium, which is a member selected from acid fast bacteria, including Mycobacterium species; bacilli, including Bacillus species, Corynebacterium species (also Propionibacterium) and Cloetridium species; filamentous bacteria, including Actinomycee species and Streptomyces species; bacilli, such as Peeudomonae species, Brucilla species, Agrobacterium species, Bordetella species, Eecherichia species, Shigella species, Yereinia species, Salmonella species, Klebsiella species, En erobacter species, Haemophilus epecies, species of Pasteurella and Streptobacillue species; species of spirochetes, Campylobacter species, Vibrio species and intracellular bacteria including Rickettsiae species and Chl amydi a species. In an exemplary embodiment, the microorganism is a virus. In an exemplary embodiment, the virus is a selected member of hepatitis A virus, human rhinovirus, yellow fever virus, human respiratory coronavirus, severe acute respiratory syndrome (SARS) virus, respiratory syncytial virus, influenza virus, parainfluenza virus 1-4, human immunodeficiency virus 1 (HIV-1), human immunodeficiency virus 2 (VTH-2), herpes simplex virus 1 (HSV-1), herpes simplex virus 2 (HSV-2), human cytomegalovirus (HCMV), varicella zoster virus , Epstein-Barr virus (EBV), poliovirus, Coxsackie virus, ecovirus, rubella virus, tropic neuroderma virus, smallpox virus, papovirus, rabies virus, dengue virus, West Nile virus and SARS virus. In another exemplary embodiment, the virus is a member selected from picornaviridae, flaviviridae, coronaviridae, paramyxoviridae, orthomyxoviridae, retroviridae, herpeeviridae and hepadnaviridae. In another exemplary embodiment, the virus is a selected member of a virus included in the following table: Table A Virus Category of Viruses Relevant Human Infections RNA Viruses Picomaviridae Polio Human Hepatitis A Human Rinovirus Togaviridae and Rubella - German Measles Flaviviridae Yellow Fever Coronaviridae Human Respiratory Coronavirus (HCV) Severe Acute Respiratory Syndrome (SAR) Lyssavir? S- Rabies Rhabdoviridae Paramyxovirus - Paramyxoviridae Mumps Morbillvirus - measles Pneumovirus - respiratory syncytial virus Orthomyxoviridae Influenza AC Bunyavirus - Bunyamwera (BUN) Hantavir? s - Hantaan (HTN) Nairevirus - Crimean hemorrhagic fever - Bunyaviridae Congo (CCHF) Phlebovirus - sandfly virus (SFN) Uukuvirus - Uukuniemi (UUK) ) Valley Fever fl / ft (RVFN) Junin - Argentine hemorrhagic fever Arenaviridae Machupo - Bolivian hemorrhagic fever Lassa - Lassa fever LC / W aseptic lymphocytic chymomeningitis Rotovirus Reoviridae Reovirus orbivirus Human immunodeficiency virus 1 Retrovireidae (HIV-1) immunodeficiency Human 2 (HIV-2) Simian immunodeficiency virus (SIV) DNA virus Papovaviridae Pediatric kidney-related viruses Adenoviridae Human respiratory distress and some ocular settling infections Deep parvoviridae Human gastro-intestinal distension (Norwalk virus) herpes simplex 1 (HSV-1) Herpes simplex virus 2 (HSV-2) Herpesviridae Human cytomegalovirus (HCMV) Varicella zoster virus (VZV) Epstein-Barr virus (EBV) Herpes simplex virus 6 (HHV6) Poxviridae Ortopoxivirus is sub-genus for smallpox Hepadnaviridae Hepatitis B virus (HBV) Hepatitis C virus (HCV) In another exemplary embodiment, the microorganism is a parasite. In an exemplary embodiment, the parasite is a selected member of Plasmodium falciparum, P. vivax, P. ovale, P. malariae, P. berghei, Leishmania donovani, L. infantum, L. chagaei, L. Mexican, L amazoneneie, L. venezueleneie, L. tropice, L. major, L minor, L. aethiopica, L. biana braziliensie, L. (V.) guyanensie, L. (V.) panameneie, L. (V.) peruviana, Trypanosoma brucei rhodesiense, T. brucei gambiense, T. cruzi, Giardia intestinal, -G. lambda, Toxoplaema gondii, Entamoeba hietolytica, Tricomonae vaginalis, Pneumocyetie carinii and Cryptoeporidium parvum. SAW. Methods for Treating or Preventing Infections In another aspect, the invention provides a method for treating or preventing an infection. The method includes administering to the animal a therapeutically effective amount of the compound of the invention, sufficient to treat or prevent infection. In an exemplary embodiment, the compound is a compound described herein. In another exemplary embodiment, the compound has a structure according to formulas (I) to (Iak) and (II) to (XI). In another exemplary embodiment, the compound has a structure that is described in Figures 19A-19K. In another exemplary embodiment, the compound has a structure that is described in Figures 20A-20H. In another exemplary embodiment, the animal is a selected member of human, cattle, deer, reindeer, goat, honey bee, pig, sheep, horse, cow, bull, dog, guinea pig, gerbil, rabbit, cat, camel, yack , elephant, ostrich, otter, chicken, duck, goose, guinea fowl, pigeon, swan and turkey. In another exemplary embodiment, the animal is a human. In another exemplary embodiment, the animal is a selected member of a human, livestock, goat, pig, sheep, horse, cow, bull, dog, guinea pig, gerbil, rabbit, cat, chicken and turkey. In another exemplary embodiment, the invention is a member selected from a systemic infection, a skin infection, and an ungular, periungular or subungual infection. In another exemplary embodiment, the treatment of a disorder or condition occurs through the inhibition of an editing domain of an aminoacyl tRNA synthetase. SAW. a) Methods for Treating or Preventing Ungular and / or Periungular Infections In another aspect, the invention provides a method of treating or preventing an ungular and / or periungular infection. The method includes administering to the animal a therapeutically effective amount of a compound or pharmaceutical formulation of the invention, sufficient to treat or prevent infection. In another exemplary embodiment, the method includes administering the compound or pharmaceutical formulation of the invention to a site that is a selected member of the skin, nail, hair, hoof, claw and skin surrounding the nail, hair, hoof and claw. SAW. a) 1) Onychomycosis Onychomycosis is a disease of the nail caused by yeast, dermatophytes or other fungi, and represents approximately 50% of all nail disorders. Infection in the toenails is equivalent to about 80% of the incidence of onychomycosis, while fingernails are affected in about 20% of cases. Dermatophytes are the most frequent cause of invasion of the nail plate, particularly in onychomycosis of the toenails. Onychomycosis caused by a dermatophyte is called Tinea unguium. Trichophyton rubrum is by far the most frequently isolated dermatophyte, followed by T. mentagrophytee. Distal subungual onychomycosis is the most common presentation of tinea unguium, with the main entrance site through the hyponychium (thickened epidermis below the free distal end of a nail) progressing over time to include the nail bed and plaque of the nail. Discoloration, onycholysis and accumulation of subungual remains and dystrophy of the nail plate characterize the disease. The disease adversely affects the quality of life of its victims, with subsequent complaints varying from unpleasant nails and discomfort with the use of shoes, to more serious complications including secondary bacterial infections. Many methods are known for the treatment of physical infections, including the oral and topical use of antibiotics (e.g., nystatin and amphotericin B), imidazole antifungal agents such as miconazole, clotrimazole, fluconazole, econazole and sulconazole and fungal agents that they are not imidazole such as the allylamine, terminfin and naftifine derivatives, and the benzylamine butenafine. however, onychomycosis has proven to be resistant to most treatments. Mycotic infections of the nail reside in an area difficult to access by conventional topical treatment and antifungal drugs can not easily penetrate the nail plate or reach the sites of infection under the nail. Therefore, onychomycosis has traditionally been treated by oral administration of anti-fungal drugs; however, this is clearly undesirable due to the potential for side effects of these drugs, in particular those caused by the more potent antifungal drugs such as itraconazole and ketoconazole. An alternative onychomycosis treatment method is by removing the nail before treating with a topically active antifungal agent; this method of treatment is equally undesirable. Systemic antifungal agents require prolonged use and have the potential for significant side effects. Topical agents have usually been of little benefit, mainly due to a deficiency penetration of the antifungal agents into and through the nail mass. In an exemplary embodiment, the invention provides a method for treating or preventing onychomycosis. The method includes administering to a human or animal a therapeutically effective amount of a compound of the invention, or a pharmaceutical formulation of the invention, sufficient to treat or prevent onychomycosis. In another exemplary embodiment, the method includes administering the pharmaceutical formulation of the invention to a site that is a selected member of the skin, nail, hair, hoof, claw and skin surrounding the nail, hair, claw and hoof. In another exemplary embodiment, the pharmaceutical formulation includes a compound described herein. The method includes administering to a human or animal a therapeutically effective amount of 1,3-dihydro-5-fluoro-l-hydroxy-2, 1-benzoxazole, sufficient to treat or prevent onychomycosis. SAW. a) 2) Other Ungular Infections and Periungular In an exemplary embodiment, the invention provides a method for treating or preventing an ungular or periungular infection in a human or an animal. This method comprises administering to the human or animal a therapeutically effective amount of a compound of the invention, thereby treating or preventing ungular or periungular infection. In an exemplary embodiment, the ungular or periungular infection is onychomycosis. In an exemplary embodiment, the ungular or periungular infection is a selected member of: onychomycosis, chloronychia, paronychias, erysipeloid, onychorhexis, gonorrhea, swimming pool granuloma, larva migrans, leprosy, Orf nodule, milkman's nodules, herpetic whitlow, acute bacterial perionixis , chronic perionixis, sporotrichosis, syphilis, verrucous complexion due to tuberculosis, tularemia, tungiasis, peri-subungual warts, zone, nail dystrophy (trachyonychia) and dermatological diseases with an effect on the nails, such as psoriasis, pustular psoriasis, alopecia aerata, pustular parakeratosis, contact dermatosis, Raiter syndrome, psoriasiform acral dermatitis, lichen planus, idiopathic nail atrophy, clear lichen, striated lichen, inflammatory linear warty epidermal nevus (IL VEN), alopecia, pemphigus, pemphigus bullosa, epidermolysis acquired blister, Darier's disease, pityriasis rubra pilaris, palmoplantar keratoderma, contac eczema cto, polymorphic erythema, sama, Bazex syndrome, systemic scleroderma, systemic lupus erythematosus, chronic lupus erythematosus, dermatomyositis. The compounds and pharmaceutical formulations of the invention useful for ungular and periungular applications also find application in the cosmetics field, in particular for the treatment of nail irregularities, coilonychia, Beau lines, longitudinal grooving, ingrown nails. In an exemplary embodiment, the infection is of skin, hair, nails, claw or hoof, hair, ear and eyes and is a selected member of sporotrichosis, fungal keratitis, oculomicosis by extension, endogenous oculomicosis, lobomycosis, mycetoma, stone, pityriasis versicolor, Tinea corporie, Tinea crurie, Tinea pedis, Tinea barbae, Tinea capi tis, Tinea nigra, otomycosis, tinea favoea, cromomycosis, and Tinea imbricata. In an exemplary embodiment, the compound useful for treating these infections is 1,3-dihydro-5-fluoro-l-hydroxy-2, 1-benzoxazole. X. b) Methods for treating Systemic Diseases In another aspect, the invention provides a method for treating a systemic disease. The method includes contacting an animal with a compound of the invention. The delivery method for the treatment of systemic diseases can be oral, intravenous, transdermal, by inhalation, intraperitoneal and subcutaneous. In an exemplary embodiment, the compound administered is 1,3-dihydro-5-fluoro-1-hydroxy-2, 1-benzoxazole. In an exemplary embodiment, the infection is systemic and is a selected member of candidiasis, aspergillosis, coccidioidomycosis, cryptococcosis, histoplasmosis, blastomycosis, paracoccidioidomycosis, zygomycosis, pheohipomycosis, and rhinosporidiosis. SAW. c) Methods for Treating Diseases Including Virus The compounds of the invention are useful for the treatment of diseases of both animals and humans, including viruses. In an exemplary embodiment, the disease is a selected member of hepatitis A-B-C, yellow fever, respiratory syncytial disease, influenza, AIDS, herpes simplex, smallpox, varicella zoster, and Epstein-Barr disease. SAW. d) Methods for Treating Diseases Including The Compounds of the invention are useful for the treatment of both animal and human diseases that include parasites. In an exemplary embodiment, the disease is a selected member of malaria, Chagas disease, Leishmaniasis, African sleeping sickness (African human trypanosomiasis), giardiasis, toxoplasmosis, amebiasis and cryptosporidiosis. In any of the methods according to the present invention shown above, it is preferred that the aminoacyl tRNA synthetase is an aminoacyl tRNA synthetase comprising an editing domain. The editing domain is encoded by a portion of the aminoacyl tRNA synthetase involved in proofreading. The editing domain is preferably encoded by a portion of DNA having at least conserved residues in comparison after alignment with the editing site of leucyl tRNA synthetase, valil tRNA synthetase and isoleucyl tRNA synthetase. Most preferably the synthetase is selected from the group consisting of the valil tRNA synthetase, isoleucyl tRNA, leucyl tRNA, alanyl-tRNA synthetase, prolyl-tRNA synthetase, threonyl-tRNA synthetase, phenyl-tRNA synthetase and lysyl-tRNA synthetase which are known having an editing or domain site (see for RS Baldwin, AN and Berg, P. (1966) J. Biol. Chem. 241, 839-845 and Eldred, EW and Schimmel, PR (1972) J. Biol. Chem. 247, 2961-2964; for Val RS, Fersht, A.R. and Kaethner, M.M. (1976) Biochemistry, 15 (15), 3342-3346; for Leu RS, English, S. et al., (1986) Nucleic Acids Research. 14 (19), 7529-7539; for Ala RS, Tsui, W. C. and Fersht, A. R. (1981) Nucleic Acids Research. 9, 7529-7539; for Pro RS, Beuning, P. J. and Musier-Forsyth, K. (2000) PNAS. 97 (16), 8916-8920; for Thr RS, Sankaranarayanan, R. et al., (2000) Nat. Struct. Biol. 7, 461-465 and Musier-Foryth, K. and Beuning, P. J. (2000) Nat. Struct. Biol. 7, 435-436; for PheRS, Yarus, M. (1972) PNAS. 69, 1915-1919 and for LysRS, Jakubowski, H. (1997) Biochemistry, 36, 11077-11085. VII. Methods of Penetration of the Nail It is believed that poor penetration of the active agent through the hoof or nail plate and / or excessive binding to keratin, (the main protein in the nails and hair) are the reasons for poor effectiveness of 8% ciclopirox p / p in commercial lacquer and other topical treatments that have failed in clinical trials. In mild cases of onychomycosis, the pathogenic fungi reside on the nail plate only. In moderate to severe cases, pathogenic fungi establish a presence on the nail plate and on the nail bed. If the infection is cleared from the nail plate but not from the nail bed, the fungal pathogen can re-infect the nail plate. Therefore, to treat onychomycosis effectively, the infection must be removed from the nail plate and the nail bed. To do this, the active agent must penetrate and disseminate substantially along the nail plate and the nail bed. It is believed that for an active agent to be effective once disseminated throughout the infected area, it must be bioavailable to the fungal pathogen and must not bind so closely to keratin that the drug can not inhibit growth or kill infectious fungi. An understanding of the morphology of the nail plate suggests certain physicochemical properties of an active agent that could facilitate the penetration of the nail plate. The desired physicochemical properties are described throughout the present. The tested compounds of the present invention are capable of penetrating the nail plate and were also active against Trichophyton rubrum and mentagrophytee and other species. In addition, the tested compounds are also active against Trichophyton rubrum in the presence of 5% keratin powder. In an exemplary embodiment, the invention provides a method for killing or inhibiting the growth of a microorganism present in a human nail unit, wherein the human nail unit comprises a nail plate. The method comprises contacting a dorsal layer of the nail plate with a compound capable of penetrating the nail plate, traversing the nail plate to the nail bed underlying the nail plate and making contact with the nail plate. the microorganism, under sufficient conditions for the compound to penetrate the nail plate. In this embodiment, the compound has a molecular weight between about 100 Da and about 200 Da, a log P value of between about 1.0 and about 2.6, a solubility in water of more than about 0.1 mg / mL octanol / water saturated and a MIC of less than 16 μg / mL against the microorganism, thus killing or inhibiting the growth of the microorganism. In an exemplary embodiment, the compound has a structure according to formula (I) described herein. In another exemplary embodiment, the compound has a structure according to formula (Ia) - (Iaa) described herein. In another exemplary embodiment, the compound has a structure according to a member selected from formula (I) - (Iaa), wherein R9a, R10a, Rlla and R12a are independently selected members independently selected from H, halogen, cyano , nitro, substituted or unsubstituted methoxy, substituted or unsubstituted methyl, substituted or unsubstituted ethoxy, substituted or unsubstituted ethyl, trifluoromethyl, substituted or unsubstituted hydroxymethyl, substituted or unsubstituted hydroxyalkyl, substituted or unsubstituted benzyl, substituted or unsubstituted phenyl, substituted or unsubstituted phenyloxy, substituted or unsubstituted phenylmethoxy, substituted or unsubstituted thiophenyloxy I pyridinyloxy substituted or unsubstituted, substituted pyrimidinyloxy or unsubstituted, substituted or unsubstituted bencilfurano, substituted or unsubstituted methylthio, I mercaptomethyl substituted or unsubstituted, mercaptoalkyl substituted or unsubstituted, substituted or unsubstituted phenylthio, substituted tiofeniltio or unsubstituted phenylmethylthio substituted or unsubstituted, substituted or unsubstituted pyridinylthio, substituted or unsubstituted pyrimidinylthio, substituted or unsubstituted benciltiofuranilo, substituted or unsubstituted phenylsulfonyl, substituted or unsubstituted benzylsulfonyl, substituted or unsubstituted phenylmethylsulfonyl, substituted or tiofenilsulfonilo sustitu gone, -pyridinylsulfonyl substituted or unsubstituted, substituted pirimidinilsulfonilo or not, substituted sulfonamidyl or not, substituted phenylsulfinyl or not, substituted benzylsulfinyl or not, substituted fenilmetilsulfinilo or not, substituted tiofenilsulfinilo or not, substituted piridinilsulfinilo or unsubstituted, I pirimidinilsulfinilo substituted or unsubstituted, substituted or unsubstituted amino, alkylamino substituted or unsubstituted dialkylamino substituted or unsubstituted, substituted trifluoromethylamino or unsubstituted aminomethyl substituted or unsubstituted, alkylaminomethyl substituted or unsubstituted, dialkylaminomethyl substituted or unsubstituted, arilaminometilo substituted or unsubstituted, substituted or unsubstituted benzylamino, substituted or unsubstituted phenylamine, substituted or unsubstituted thiophenylamino, substituted or unsubstituted pyridinylamino, substituted or unsubstituted pyrimidinylamino, substituted or unsubstituted indolyl ituido, substituted or unsubstituted morpholino, substituted or unsubstituted alkylamido, substituted or unsubstituted arylamido, substituted or unsubstituted ureido, substituted or unsubstituted carbamoyl, and substituted or unsubstituted piperizinyl. In another exemplary embodiment, R9a, R10a, Rlla and R12a are members independently selected from H, fluoro, chloro, bromo, nitro, cyano, amino, methyl, hydroxylmethyl, trifluoromethyl, methoxy, trifluoromethoxy, ethyl, diethylcarbamoyl, pyridin-2-yl. pyridin-3-yl, pyridin-4-yl, pyrimidinyl, piperazino, piperizinyl, piperizinocarbonilo, piperizinilcarbonilo, carboxyl, 1-tetrazolyl, 1-ethoxycarbonylmethoxy, carboxymethoxy, thiophenyl, 3- (butylcarbonyl) phenylmethoxy, lH-tetrazol-5- yl, 1-etoxicarbonilmetiloxi-, 1-etoxicarbonilmetilo-, 1-etoxicarbonilo-, carboximetoxi-, thiophen-2-yl, thiophen-2-iltio-, thiophen-3-yl, thiophen-3-ylthio, 4-fluorophenylthio, butilcarbonilf nylmethoxy, butylcarbonylphenylmethyl, butylcarbonylmethyl, 1- (piperidin-1-yl) carbonyl) methyl, 1- (piperidin-1-yl) carbonyl) methoxy, 1- (piperidin-2-yl) carbonyl) ethoxy, 1- (piperidine) 3-yl) carbonyl) methoxy, 1- (4- (pyrimidin-2-yl) piperazin-1-yl) carbonyl) methoxy, 1- (4- (pyrimidin-2-yl) piperazin-1-yl) carbonyl) methyl, l- (4- (pyrimidi n-2-yl) piperazin-1-yl) carbonyl, 1-4- (pyrimidin-2-yl) piperazin-1-yl, 1- (4- (pyridin-2-yl) piperazin-1-yl) carbonyl ), 1- (4- (pyridin-2-yl) piperazin-1-yl) carbonylmethyl, (1- (4- (pyridin-2-yl) piperazin-1-yl) carbonyl) -methoxy), 1- ( 4- (pyridin-2-yl) piperazin-1-yl, 1H-indol-1-yl, morpholino-, morpholinyl, morpholinocarbonyl, morpholinylcarbonyl, phenylureido, phenylcarbamoyl, acetamide, 3- (phenylthio) -lH-indole-1- ilo, 3- (2-cyanoethylthio) -lH-indol-1-yl, benzylamino, 5-methoxy-3- (phenylthio) -lH-indol-1-yl, 5-methoxy-3- (2-cyanoethylthio) - lH-indol-1-yl)), 5-chloro-lH-indol-1-yl, 5-chloro-3- (2-cyanoethylthio) -lH-indol-1-yl), dibenzylamino, benzylamino, 5- chloro-3- (phenylthio) -lH-indol-1-yl)), 4- (lH-tetrazol-5-yl) phenoxy, 4- (lH-tetrazol-5-yl) phenyl, 4- (lH-tetrazol-5-yl) phenylthio, 2-cyanophenoxy, 3-cyanophenoxy, 4-cyanophenoxy, 2-cyanophenylthio, 3-cyanophenylthio, 4-cyanophenylthio, 2-chlorophenoxy, 3-chlorophenoxy, 4-chlorophenoxy, 2-fluorophenoxy, 3-fluorophenoxy, 4-fluorophenoxy, 2-cyanobenzyloxy, 3-cyanobenzyloxy, 4-cyanobenzyloxy, 2-chlorobenzyloxy, 3-chlorobenzyloxy, 4-chlorobenzyloxy, 2-fluorobenzyloxy, 3-fluorobenzyloxy and 4-fluorobenzyloxy. In another exemplary embodiment, wherein R9a is H and R12a is H. In another exemplary embodiment, the compound is 1,3-dihydro-5-fluoro-l-hydroxy-2, 1-benzoxazole. In another exemplary embodiment, the invention provides a method for treating a disease caused by a microorganism present in a human nail unit, wherein the human nail unit comprises a nail plate, the method comprising: contacting a back plate of the nail plate with a compound able to penetrate the nail plate, traverse the nail plate to a bed of the nail that underlies the nail plate and make contact with the microorganism, under conditions sufficient for the compound penetrate the nail plate and treat the disease. In this embodiment, the compound has a molecular weight of between about 100 Da and about 200 Da; a log P value of between about 1.0 and about 2.6; a solubility in water of more than about 0.1 mg / mL of octanol / saturated water and a MIC of less than 16 μg / mL against the microorganism, thereby treating the disease. In an exemplary embodiment, the compound has a structure according to formula (I) described herein. In another exemplary embodiment, the compound has a structure that is a member selected from formula (Ia) - (Iaa) described herein. In another aspect, the invention provides a method for delivering a compound from the dorsal layer of the nail plate to the nail bed. This method comprises contacting the cell with a compound capable of penetrating the nail plate, under conditions sufficient to penetrate the nail. The compound has a molecular weight of between about 100 and about 200 Da. The compound also has a log P value of between about 1.0 and about 2.6. The compound further has a solubility in water of between about 0.1 mg / mL and 1 g / mL octanol / saturated water, thereby supplying the compound. In a preferred embodiment, the physicochemical properties of the compound of the invention, described by the predictive amounts for migration of the compound through the nail plate, including, but not limited to, molecular weight, log P and water solubility, and similar, are effective to provide substantial penetration of the nail plate. Compounds with a molecular weight of less than 200 Da penetrate the nail plate in a manner superior to the commercially available treatment for onychomycosis. In one embodiment of the present invention, the compound has a molecular weight of between 130 and 200. In another embodiment of this invention, the compound has a molecular weight of from about 140 to about 200 Da. In another embodiment of this invention, the compound has a molecular weight of from about 170 to about 200 Da. In another embodiment of this invention, the compound has a molecular weight of from about 155 to about 190 Da. In another embodiment of this invention, the compound has a molecular weight of from about 165 to about 185 Da. In another embodiment of this invention, the compound has a molecular weight of from about 145 to about 170 Da. In another modality, the molecular weight is either 151.93 or 168.39 Da. In one embodiment of the present invention the compound has a log P value of between about -3.5 to about 2.5. In another exemplary embodiment, the compound has a log P value of about -1.0 to about 2.5. In another exemplary embodiment, the compound has a log P value of about -1.0 to about 2.0. In another exemplary embodiment, the compound has a log P value of about -0.5 to about 2.5. In another exemplary embodiment, the compound has a log P value of about -0.5 to about 1.5. In another exemplary embodiment, the compound has a log value of from about 0.5 to about 2.5. In another exemplary embodiment, the compound has a log P value of from about 1.0 to about 2.5. In yet another exemplary embodiment, the compound has a log P value of 1.9 or 2.3. Also contemplated by the present invention is a compound with a log P value of less than 2.5, with a molecular weight of less than 200 Da, which is still capable of penetrating the nail layer. In one embodiment of the present invention the compound has a solubility in water of between about 0.1 mg / mL to 1 g / mL in water saturated with octanol. In one embodiment of the present invention the compound has a solubility in water of between 0.1 mg / mL and 100 mg / mL. In another embodiment of this invention, the compound has a solubility in water of about 0.1 mg / mL and 10 mg / mL. In another embodiment of this invention, the compound has a solubility in water of about 0.1 mg / mL and 1 mg / mL. In another embodiment of this invention, the compound has a solubility in water of about 5 mg / mL and 1 g / mL. In another embodiment of this invention, the compound has a solubility in water of about 10 mg / mL and 500 g / mL. In another embodiment of this invention, the compound has a solubility in water of about 80 mg / mL and 250 mg / mL. In an exemplary embodiment, the present invention provides a compound with a log P value selected from a previous scale, with a molecular weight selected from a previous scale, which is still capable of penetrating the nail plate.

In an exemplary embodiment, the present invention provides compounds with a molecular weight selected from a scale above, with a solubility in water selected from a previous scale, which are still capable of penetrating the nail plate. In an exemplary embodiment, the present invention provides compounds with a log P selected from a previous scale, with a solubility in water selected from a previous scale, which are still capable of penetrating the nail plate. In an exemplary embodiment, the present invention provides compounds with a molecular weight selected from a previous scale, with a log P selected from a previous scale with a solubility in water selected from a previous scale, which are still capable of penetrating the plate of the a. The penetration of the nail by the active ingredient can be carried out by the polarity of the formulation. However, the polarity of the formulation is not expected to have as much influence on the penetration of the nail as some other factors, such as the molecular weight or log P of the active ingredient. The presence of penetration enhancing agents in the formulation is likely to increase the penetration of the active agent when compared to similar formulations that do not contain penetration enhancing agent. Some examples of molecules with optimal physicochemical properties are given in the following table.

Compound 3 below is an example of a compound similar in molecular weight to ciclopirox, and like cyclopirox, it penetrates the nail plate in a deficient manner.

In a preferred embodiment in topical formulations including a compound described herein have a total molecular weight of less than 200 Da, a log P of less than 2.5 and a minimum inhibitory concentration against Trichophyton rubrum that substantially has no changes in the presence of 5% keratin. The efficiency coefficient (defined as flow over MiC) of a compound also informs someone of ability with respect to the compound can be effective to kill a microorganism, inhibit the growth of a microorganism or treat a disease that is caused by a microorganism present in a human nail unit, wherein the human nail unit comprises a nail plate. The method comprises: contacting a dorsal plate of the nail plate with a compound capable of penetrating the nail plate, traveling through the nail plate to a bed of the nail that underlies the nail plate and making contact with the microorganism, under conditions sufficient for the compound to penetrate the nail plate and treat the disease, wherein the compound has a coefficient of effectiveness greater than 10. In an exemplary embodiment, the compound has an efficacy coefficient between about 10 and about 1000. In an exemplary embodiment, the compound has an efficiency coefficient of between about 30 and about 100. In an exemplary embodiment, the compound has a coefficient of efficacy of between about 100 and about 500. In an exemplary embodiment, the compound has a coefficient of effectiveness of between about 25 and about 200. This invention is also directed further to methods for t ratar a fungal infection mediated at least in part by dermatophytes, Trichophyton, Microeporum or Epidermophyton, or a yeast-type fungus including Candida species, in a human or an animal, the method comprises administering to a human or an animal, which has been diagnosed with the fungal infection or at risk of developing the fungal infection, a pharmaceutical composition comprising a pharmaceutically acceptable diluent and a therapeutically effective amount of a compound described herein or mixtures of one or more of these compounds. In an embodiment, the infection is onychomycosis. The compounds contemplated by the present invention may have broad spectrum antifungal activity and thus may be candidates for use against other cutaneous fungal infections. The methods provided in this aspect of the invention are useful in the penetration of nails and hooves, as well as the treatment of ungular and periungular conditions. VIII. Pharmaceutical Formulations In another aspect, the invention is a pharmaceutical formulation that includes: (a) a pharmaceutically acceptable excipient and (b) a compound of the invention. In another aspect, the invention is a pharmaceutical formulation that includes: (a) a pharmaceutically acceptable excipient and (b) a compound having a structure that is a member selected from formulas (I), (a), (Ib), (le), (Id), (le), (If), (ig), (Ih), (Ii), (Ij), (Ik), (II), (Im), (In), (lo ), (ip), Iq), dr), (Is), (It), (Iu), (Iv), (Iw), (Iz), (iaa), (Lab), (lac), (Iad) ), (Iae), (Iaf), (lag), (Iah), (Iai), (Iaj), (Iak), (II), (Lia), (Ilb), (Lie), (Lid), (III). In another aspect, the invention is a pharmaceutical formulation that includes: (a) a pharmaceutically acceptable excipient and (b) a compound having a structure according to the formulas (VIII), (Villa), (VlIIb), (VIIIc) , (VlIId), (VlIIe). In another aspect, the invention is a pharmaceutical formulation that includes: (a) a pharmaceutically acceptable excipient and (b) a compound having a structure that is a member selected from D1-D19, E1-E19, (VIII), (Villa) ), (VlIIb), (VIIIc), (VlIId), (VlIIe). In another aspect, the invention is a pharmaceutical formulation that includes: (a) a pharmaceutically acceptable excipient and (b) an acyclic boronic ester of the invention. In an exemplary embodiment, the compound is described in Figures 19A-19K. In another exemplary embodiment, the compound is described in Figures 20A-20H. In another exemplary embodiment, the invention is a pharmaceutical formulation that includes: (a) a pharmaceutically acceptable excipient and (b) an acyclic boronic ester of the invention. In another aspect, the invention is a pharmaceutical formulation comprising: (a) a pharmaceutically acceptable excipient and (b) a compound having a structure according to formula (I): where B is boron. Rla is a member selected from a negative charge, a salt counterion, H, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and heteroaryl replaced or not replaced. M is a selected member of oxygen, sulfur and NR2a. R2a is a member selected from H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl. J is a member selected from (CR3aR4a) m and CR5a. R3a, R4a and R5a are members independently selected from H, halogen, cyano, substituted or unsubstituted algeryl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl replaced. The index is not an integer selected from 0 to 2. is a member selected from C = 0 (carbonyl), (CR6aR7a) m? and CR8a. R6a, R7a and R8a are members independently selected from H, halogen, cyano, substituted or unsubstituted algeryl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl replaced. The ml index is an integer selected from 0 and 1. A is a selected member of CR9a and N. D is a selected member of CR10a and N. E is a selected member of CRlla and N.G is a member selected from Cr12a and N. R9a, R10a, Rlla and R12a are members independently selected from H, OR *, NR * R **, SR *, S (0) R *, -S (0) 2R *, -S (0) 2NR * R **, -C (0) R *, -C (0) OR *, C (0) NR * R **, nitro, halogen, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted cycloalkyl or unsubstituted, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl. Each R * and R ** are members independently selected from H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl. The combination of nitrogens (A + D + E + G) is an integer selected from 0 to 3. A selected member of R3a, R4a and R5a and a selected member of R6a, R7a and R8a, together with the atoms to which they are united, they are optionally joined to form a ring of 4 to 7 members. R3a and R4a, together with the atoms to which they are attached, optionally join to form a 4 to 7 membered ring. R6a and R7a, together with the atoms to which they are attached, optionally join to form a 4 to 7 membered ring. R9a and R10a, together with the atoms to which they are attached, optionally join to form a 4- to 7-membered ring. R10a and Rlla, together with the atoms to which they are attached, optionally join to form a 4 to 7 membered ring. Rlla and R12a, together with the atoms to which they are attached, optionally join to form a 4- to 7-membered ring. In another exemplary embodiment, there is a condition that the compound can not have a structure according to the formula (Ix): wherein R7b is a member selected from H, methyl, ethyl and phenyl. R 10b is a member selected from H, OH, NH 2, SH, halogen, substituted or unsubstituted phenoxy, unsubstituted or substituted phenylalkyloxy, substituted or unsubstituted phenytoi, and unsubstituted or substituted phenylalkylthio. Rllb is a member selected from H, OH, NH2, SH, methyl, substituted or unsubstituted phenoxy, unsubstituted or substituted phenylalkyl, unsubstituted or substituted phenylthio, and unsubstituted or substituted phenylalkylthio. In another exemplary modality, there is a condition that the compound can not have a structure according to the formula (Ix) wherein Rlb is a member selected from a negative charge, H and a salt counterion. In another exemplary embodiment, there is a condition that the compound can not have a structure according to the formula (Ix) wherein R10b and Rllb are H. In another exemplary embodiment, there is a condition that the compound can not have a structure according to the formula (Ix) wherein one member selected from R10b and Rllb is H and the other member selected from R10b and Rllb is a member selected from halo, methyl, cyano, methoxy, hydroxymethyl and p-cyanophenyloxy. In another exemplary embodiment, there is a condition that the compound can not have a structure according to formula (Ix) wherein R 10b and Rllb are members independently selected from fluoro, chloro, methyl, cyano, methoxy, hydroxymethyl and p-cyanophenyl . In another exemplary embodiment, there is a condition that the compound can not have a structure according to the formula (Ix) wherein Rlb is a member selected from a negative charge, H and a salt counterion; R7b is H; R10b is F and Rllb is H. In another exemplary embodiment, there is a condition that the compound can not have a structure according to formula (Ix) wherein Rllb and R12b, together with the atoms to which they are attached, are join to form a phenyl group. In another exemplary embodiment, there is a condition that the compound can not have a structure according to formula (Ix) wherein R 1 is a member selected from a negative charge, H and a salt counterion; R7b is H; R10b is 4-cyanophenoxy and Rllb is H. In another exemplary embodiment, there is a condition that the compound can not have a structure according to the formula (Iy) wherein R10b is a member selected from H, halogen, CN and C? -4 al-substituted or unsubstituted alkenyl. In an exemplary embodiment, the pharmaceutical formulation comprises a compound having a structure according to formula (la): In another exemplary embodiment, each R3a and R4a is a member independently selected from H, cyano, substituted or unsubstituted methyl, substituted or unsubstituted ethyl, trifluoromethyl, substituted or unsubstituted hydroxymethyl, substituted or unsubstituted hydroxyalkyl, substituted or unsubstituted benzyl. , substituted or unsubstituted phenyl, unsubstituted or substituted mercaptomethyl, substituted or unsubstituted mercaptoalkyl, substituted or unsubstituted aminomethyl, unsubstituted or substituted alkylaminomethyl, unsubstituted or substituted dialkylaminomethyl, unsubstituted or substituted arylaminomethyl, unsubstituted or substituted indolyl and amido replaced or not replaced. In another exemplary embodiment, each R3a and R4a is a member independently selected from cyano, substituted or unsubstituted methyl, substituted or unsubstituted ethyl, trifluoromethyl, substituted or unsubstituted hydroxymethyl, substituted or unsubstituted hydroxyalkyl, substituted or unsubstituted benzyl, phenyl substituted or unsubstituted, substituted or unsubstituted mercaptomethyl, substituted or unsubstituted mercaptoalkyl, substituted or unsubstituted aminomethyl, substituted or unsubstituted alkylaminomethyl, substituted or unsubstituted dialkylaminomethyl, substituted or unsubstituted arylaminomethyl, unsubstituted or substituted indolyl and substituted amido or not replaced In another exemplary embodiment, each R3a and Ra is a member selected from H, substituted or unsubstituted methyl, substituted or unsubstituted ethyl, substituted or unsubstituted propyl, substituted or unsubstituted isopropyl, substituted or unsubstituted butyl, substituted t-butyl. or unsubstituted, substituted or unsubstituted phenyl and substituted or unsubstituted benzyl. In another exemplary embodiment, R3a and Ra is a member selected from methyl, ethyl, propyl, isopropyl, butyl, t-butyl, phenyl and benzyl. In another exemplary embodiment, R3a is H and Ra is a member selected from methyl, ethyl, propyl, isopropyl, butyl, t-butyl, phenyl and benzyl. In another exemplary embodiment, R3a is H and R4a H. In another exemplary embodiment, R9a, R10a, Rlla and R12a is a member selected independently from H, OR *, NR * R **, SR *, -S (0) R *, -S (0) 2R *, -S (0) 2NR * R **, -C (0) R *, -C (0) CR *, -C (0) NR * R **, halogen, cyano, nitro, substituted or unsubstituted methoxy, substituted or unsubstituted methyl, substituted or unsubstituted ethoxy, substituted or unsubstituted ethyl, trifluoromethyl, substituted or unsubstituted hydroxymethyl, substituted or unsubstituted hydroxyalkyl, substituted or unsubstituted benzyl, substituted phenyl or unsubstituted, substituted or unsubstituted phenyloxy, substituted or unsubstituted phenylmethoxy, substituted or unsubstituted thiophenyloxy, substituted or unsubstituted pyridinyloxy, substituted or unsubstituted pyrimidinyloxy, substituted or unsubstituted benzylfurane, substituted or unsubstituted methylthio, unsubstituted or substituted mercaptomethyl substituted, substituted or unsubstituted mercaptoalkyl, substituted or unsubstituted phenylthio, thiophenylthio substituted or not substituted, substituted or unsubstituted phenylmethylthio, substituted or unsubstituted pyridinylthio, substituted or unsubstituted pyrimidinylthio, unsubstituted or substituted benzylthiuram, unsubstituted or substituted phenylsulfonyl, unsubstituted or substituted benzylsulfonyl, substituted or unsubstituted phenylmethylsulfonyl, substituted or unsubstituted thiophenylsulfonyl, substituted or unsubstituted pyridinylsulfonyl, substituted or unsubstituted pyrimidinylsulfonyl, substituted or unsubstituted sulfonamidyl, substituted or unsubstituted phenylsulfinyl, substituted or unsubstituted benzylsulfinyl, unsubstituted or substituted phenylmethylsulphinyl, substituted or unsubstituted thiophenylsulfinyl, substituted or unsubstituted pyridinylsulfinyl, substituted pyrimidinylsulfinyl or not replaced, substituted or unsubstituted amino, substituted or unsubstituted alkylamino, substituted or unsubstituted dialkylamino, substituted or unsubstituted trifluoromethylamino, substituted or unsubstituted aminomethyl, substituted or unsubstituted alkylaminomethyl, substituted or unsubstituted dialkylaminomethyl, substituted or unsubstituted arylaminomethyl, benzylamino substituted or unsubstituted, substituted or unsubstituted phenylamine, substituted or unsubstituted thiophenylamino, substituted or unsubstituted pyridinylamino, substituted or unsubstituted pyridinylamino, substituted or unsubstituted indolyl, substituted or unsubstituted morpholino, substituted or unsubstituted alkylamido, substituted arylamido or unsubstituted, substituted or unsubstituted ureido, substituted or unsubstituted carbamoyl and substituted or unsubstituted piperizinyl. In an exemplary embodiment, Ra, R10a, Rlla and R12a are selected from the foregoing list of substituents with the exception of -C (0) R *, -C (0) OR *, -C (0) NR * R **. In another exemplary embodiment, R6a, R7a, R9a, R10a, Rlla and R12a are members independently selected from fluoro, chloro, bromo, nitro, cyano, amino, methyl, hydroxylmethyl, trifluoromethyl, methoxy, trifluoromethoxy, ethyl, diethylcarbamoyl, pyridin-2. -yl, pyridin-3-yl, pyridin-4-yl, pyrimidinyl, piperazino, piperizinyl, piperizinocarbonyl, piperizinylcarbonyl, carboxyl, 1-tetrazolyl, 1-ethoxycarbonylmethoxy, carboxymethoxy, thiophenyl, 3- (butylcarbonyl) phenylmethoxy, lH-tetrazol- 5-yl, 1-ethoxycarbonylmethyloxy-, 1-ethoxycarbonylmethyl-, 1-ethoxycarbonyl-, carboxymethoxy-, thiophen-2-yl, thiophen-2-ylthio-thiophen-3-yl, thiophen-3-ylthio, 4-fluorophenylthio, butylcarbonylphenylmethoxy, butylcarbonylphenylmethyl, butylcarbonylmethyl, 1- (piperidin-1-yl) carbonyl) methyl, 1- (piperidin-1-yl) carbonyl) methoxy, 1- (piperidin-2-yl) carbonyl) methoxy, 1- (piperidine) 3-yl) carbonyl) methoxy, 1- (4- (pyrimidin-2-yl) piperazin-1-yl) carbonyl) methoxy, 1- (4- (pyrimidin-2-yl) piperazin-1-yl) carbonyl) methyl, 1- (4- (pyrimidin-2-yl) piperazin-1-yl) carbonyl, 1-4- (pyrimidin-2-yl) piperazin-1-yl, 1- (4- (pyridin-2-yl) piperazin-1-yl) carbonyl), 1- (4- (pyridin-2-yl) piperazin-1-yl) carbonylmethyl, (1- (4- (pyridin-2-yl) piperazin-1-yl) carbonyl) -methoxy), 1- (4- (pyridin-2-yl) piperazin-1-yl, 1H-indol-1-yl, morpholino-, morpholinyl, morpholinocarbonyl, morpholinylcarbonyl, phenylureido, phenylcarbamoyl, acetamide, 3- (phenylthio) -lH-indole-1 -yl, 3- (2-cyanoethylthio) -lH-indol-1-yl, benzylamino, 5-methoxy-3- (phenylthio) -lH-indol-1-yl, 5-methoxy-3- (2-cyanoethylthio) -lH-indol-1-yl)), 5-chloro-lH-indol-1-yl, 5-chloro-3- (2-cyanoethylthio) -lH-indol-1-yl),. dibenzylamino, benzylamino, 5-chloro-3- (phenylthio) -lH-indol-1-yl)), 4- (lH-tetrazol-5-yl) phenoxy, 4- (lH-tetrazol-5-yl) phenyl, 4- (lH-tetrazol-5-yl) phenylthio, 2-cyanophenoxy, 3-cyanophenoxy, 4-cyanophenoxy, 2-cyanophenylthio, 3-cyanophenylthio, 4-cyanophenylthio, 2-chlorophenoxy, 3-chlorophenoxy, 4-chlorophenoxy, 2 -fluorophenoxy, 3-fluorophenoxy, 4-fluorophenoxy, 2-cyanobenzyloxy, 3-cyanobenzyloxy, 4-cyanobenzyloxy, 2-chlorobenzyloxy, 3-chlorobenzyloxy, 4-chlorobenzyloxy, 2-fluorobenzyloxy, 3-fluorobenzyloxy, 4-fluorobenzyloxy, unsubstituted phenyl and unsubstituted benzyl. In an exemplary embodiment, the pharmaceutical formulation comprises a compound having a structure that is a member according to the following formulas: In an exemplary embodiment, the pharmaceutical formulation comprises a compound having a structure according to one of the formulas I-Io with selections of substituent for R9a, R10a, Rlla and R12a including all possibilities contained in paragraph 106 except for H. in an exemplary embodiment, the pharmaceutical formulation comprises a compound having a structure according to one of formulas Ib-Io with selections of substituent for R9a, R10a, Rlla and R12a including all possibilities contained in paragraph 107 except for H. In an exemplary embodiment, the pharmaceutical formulation comprises a compound having a formula according to formulas (Ib) - (le) wherein Rla is a selected member of H, a negative charge and a salt counterion and the remaining R group (R9a in Ib, R10a in le, Rlla in Id and R12a in le) is a member selected from fluoro, chloro, bromo, nitro, cyano, amino, methyl, hydroxylmethyl, trifluoromethyl, methoxy, trifluoromethoxy, ethyl, diethylcarbamoyl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, pyrimidinyl, piperazino, piperizinyl, piperizinocarbonyl, piperizinylcarbonyl, carboxyl, 1-tetrazolyl, 1-ethoxycarbonylmethoxy, carboxymethoxy, thiophenyl, 3- (butylcarbonyl) phenylmethoxy, 1H-tetrazol-5-yl, 1-ethoxycarbonylmethyloxy-, 1-ethoxycarbonylmethyl-, 1-ethoxycarbonyl-, carboxymethoxy-, thiophen-2-yl, thiophen-2-ylthio-, thiophen-3-yl, thiophen-3-ylthio, 4-fluorophenylthio, butylcarbonylphenylmethoxy, butylcarbonylphenylmethyl, butylcarbonylmethyl, 1- (piperidin-1-yl) carbonyl) methyl, 1- (piperidin-1-yl) carbonyl) methoxy, 1- (piperidin-2-yl) ) carbonyl) ethoxy, 1- (piperidin-3-yl) carbonyl) methoxy, 1- (4- (pyrimidin-2-yl) piperazin-1-yl) carbonyl) methoxy, 1- (4- (pyrimidine-2- il) piperazin-1-yl) carbonyl) methyl, 1- (4- (pyrimidin-2-yl) piperazin-1-yl) carbonyl, 1-4- (pyrimidin-2-yl) piperazin-1-yl, - (4- (pyridin-2-yl) piperazin-1-yl) carbonyl), 1- (4- (pyridin-2-yl) piperazin-1-yl) carbonylmethyl, (1- (4- (pyridine -2-yl) piperazin-1-yl) carbonyl) -methoxy), 1- (4- (pyridin-2-yl) piperazin-1-yl, lH-indol-1-yl, morpholino-, morpholinyl, morpholinocarbonyl, morpholinylcarbonyl, phenylureido, phenylcarbamoyl, acetamide, 3- (phenylthio) -lH-indol-1-yl, 3- (2-cyanoethylthio) -lH-indol-1-yl, benzylamino, 5-methoxy-3- (phenylthio) - lH-indol-1-yl, 5-methoxy-3- (2-cyanoethylthio) -1H-indol-1-yl), 5-chloro-lH-indol-l-yl, 5-chloro-3- (2 -cyanoethylthio) -lH-indol-1-yl)), dibenzylamino, benzylamino, 5-chloro-3- (phenylthio) -lH-indol-1-yl), 4- (lH-tetrazol-5-yl) phenoxy 4- (lH-tetrazol-5-yl) phenyl, 4- (lH-tetrazol-5-yl) phenylthio, 2-cyanophenoxy, 3-cyanophenoxy, 4-cyanophenoxy, 2-cyanophenylthio, 3-cyanophenylthio, 4-cyanophenylthio , 2-chlorophenoxy, 3-chlorophenoxy, 4-chlorophenoxy, 2-fluorophenoxy, 3-fluorophenoxy, 4-fluorophenoxy, 2-cyanobenzyloxy, 3-cyanobenzyloxy, 4-cyanobenzyloxy, 2-chlorobenzyloxy, 3-chlorobenzyloxy, 4-chlorobenzyloxy, 2 -fluorobenzyloxy, 3-fluorobenzyloxy, 4-fluorobenzyloxy. In an exemplary embodiment, the pharmaceutical formulation comprises a compound having a formula according to the formulas (If) - (Ik) wherein Rla is a selected member of H, a negative charge and a salt counterion and each of the two remaining R groups (R9a and R10a in If, R9a and Rlla in ig, R9a and R12a in Ih, R10a and Rlla in Ii, R10a and R12a in Ij, Rlla and R12a in Ik) is a member independently selected from fluoro, chloro , bromine, nitro, cyano, amino, methyl, hydroxylmethyl, trifluoromethyl, methoxy, trifluoromethoxy, ethyl, diethylcarbamoyl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, pyrimidinyl, piperazino, piperizinyl, piperizinocarbonyl, piperizinylcarbonyl , carboxyl, 1-tetrazolyl, 1-ethoxycarbonylmethoxy, carboxymethoxy, thiophenyl, 3- (butylcarbonyl) phenylmethoxy, lH-tetrazol-5-yl, 1-ethoxycarbonylmethyloxy-, 1-ethoxycarbonylmethyl-, 1-ethoxycarbonyl-, carboxymethoxy-, thiophene- 2-yl, thiophen-2-ylthio-, thiophen-3-yl, thiophen-3-ylthio, 4-fluorophenylthio, butylcarbonyl nylmethoxy, butylcarbonylphenylmethyl, butylcarbonylmethyl, 1- (piperidin-1-yl) carbonyl) methyl, 1- (piperidin-1-yl) carbonyl) methoxy, 1- (piperidin-2-yl) carbonyl) methoxy, 1- (piperidin-3-yl) carbonyl ) methoxy, 1- (4- (pyrimidin-2-yl) piperazin-1-yl) carbonyl) methoxy, 1- (4- (pyrimidin-2-yl) piperazin-1-yl) carbonyl) methyl, 1- ( 4- (pyrimidin-2-yl) piperazin-1-yl) carbonyl, 1-4- (pyrimidin-2-yl) piperazin-1-yl, 1- (4- (pyridin-2-yl) piperazin-1- il) carbonyl), 1- (4- (pyridin-2-yl) piperazin-1-yl) carbonylmethyl, (1- (4- (pyridin-2-yl) piperazin-1-yl) carbonyl) -methoxy), 1- (4- (pyridin-2-yl) piperazin-1-yl, 1H-indol-1-yl, morpholino-, morpholinyl, morpholinocarbonyl, morpholinylcarbonyl, phenylureido, phenylcarbamoyl, acetamide, 3- (phenylthio) -lH-indole -1-yl, 3- (2-cyanoethylthio) -lH-indol-1-yl, benzylamino, 5-methoxy-3- (phenylthio) -lH-indol-1-yl, 5-methoxy-3- (2- cyanoethylthio) -lH-indol-1-yl)), 5-chloro-lH-indol-1-yl, 5-chloro-3- (2-cyanoethylthio) -lH-indol-1-yl), dibenzylamino, benzylamino , 5-chloro-3- (phenylthio) -lH-indol-1-yl), 4- (lH-te trazol-5-yl) phenoxy, 4- (lH-tetrazol-5-yl) phenyl, 4- (lH-tetrazol-5-yl) phenylthio, 2-cyanophenoxy, 3-cyanophenoxy, 4-cyanophenoxy, 2-cyanophenylthio, 3-cyanophenylthio, 4-cyanophenylthio, 2-chlorophenoxy, 3-chlorophenoxy, 4-chlorophenoxy, 2-fluorophenoxy, 3-fluorophenoxy, 4-fluorophenoxy, 2-cyanobenzyloxy, 3-cyanobenzyloxy, 4-cyanobenzyloxy, 2-chlorobenzyloxy, 3- chlorobenzyloxy, 4-chlorobenzyloxy, 2-fluorobenzyloxy, 3-fluorobenzyloxy, 4-fluorobenzyloxy. In an exemplary embodiment, the pharmaceutical formulation comprises a compound having a formula according to formulas (II) - (lo) wherein Rla is a selected member of H, a negative charge and a salt counterion and each of the three remaining R groups (R9a, R10a, Rlla in (II), R9a, R10a, R12a in (Im), R9a, Rlla, R12a in (In), R10a, Rlla, R12a in (lo)) is a member independently selected of fluoro, chloro, bromo, nitro, cyano, amino, methyl, hydroxylmethyl, trifluoromethyl, methoxy, trifluoromethoxy, ethyl, diethylcarbamoyl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, pyrimidinyl, piperazino, piperizinyl , piperizinecarbonyl, piperizinylcarbonyl, carboxyl, 1-tetrazolyl, 1-ethoxycarbonylmethoxy, carboxymethoxy, thiophenyl, 3- (butylcarbonyl) phenylmethoxy, lH-tetrazol-5-yl, 1-ethoxycarbonylmethyloxy-, 1-ethoxycarbonylmethyl-, 1-ethoxycarbonyl-, carboxymethoxy -, thiophen-2-yl, thiophen-2-ylthio-, thiophen-3-yl, thiophen-3-ylthio, 4-fluorophenylthio, butylcarbonylphenylmetox i, butylcarbonylphenylmethyl, butylcarbonylmethyl, 1- (piperidin-1-yl) carbonyl) methyl, 1- (piperidin-1-yl) carbonyl) methoxy, 1- (piperidin-2-yl) carbonyl) methoxy, 1- (piperidine) 3-yl) carbonyl) methoxy, 1- (4- (pyrimidin-2-yl) piperazin-1-yl) carbonyl) methoxy, 1- (4- (pyrimidin-2-yl) piperazin-1-yl) carbonyl) methyl, 1- (4- (pyrimidin-2-yl) piperazin-1-yl) carbonyl, 1-4- (pyrimidin-2-yl) piperazin-1-yl, 1- (4- (pyridin-2-yl) ) piperazin-1-yl) carbonyl), 1- (4- (pyridin-2-yl) piperazin-1-yl) carbonylmethyl, (1- (4- (pyridin-2-yl) piperazin-1-yl) carbonyl ) -methoxy), 1- (4- (pyridin-2-yl) piperazin-1-yl, 1H-indol-1-yl, morpholino-, morpholinyl, morpholinocarbonyl, morpholinylcarbonyl, phenylureido, phenylcarbamoyl, acetamide, 3- (phenylthio ) -lH-indol-1-yl, 3- (2-cyanoethylthio) -lH-indol-1-yl, benzylamino, 5-methoxy-3- (phenylthio) -lH-indol-1-yl, 5-methoxy- 3- (2-cyanoethylthio) -lH-indol-1-yl)), 5-chloro-lH-indol-1-yl, 5-chloro-3- (2-cyanoethylthio) -lH-indol-1-yl) ), dibenzylamino, benzylamino, 5-chloro-3 - (phenylthio) -lH-indol-1-yl)), 4- (lH-tetrazol-5-yl) phenoxy, 4- (lH-tetrazol-5-yl) phenyl, 4- (lH-tetrazole-5- il) phenylthio, 2-cyanophenoxy, 3-cyanophenoxy, 4-cyanophenoxy, 2-cyanophenylthio, 3-cyanophenylthio, 4-cyanophenylthio, 2-chlorophenoxy, 3-chlorophenoxy, 4-chlorophenoxy, 2-fluorophenoxy, 3-fluorophenoxy, 4- fluorophenoxy, 2-cyanobenzyloxy, 3-cyanobenzyloxy, 4-cyanobenzyloxy, 2-chlorobenzyloxy, 3-chlorobenzyloxy, 4-chlorobenzyloxy, 2-fluorobenzyloxy, 3-fluorobenzyloxy, 4-fluorobenzyloxy. In an exemplary embodiment, the pharmaceutical formulation comprises a compound that is a member selected from: H u H OH? H PH H PH f? »Y8 PH cnr,? * O > ., "T xx» icos 5o In an exemplary embodiment, the compound of the invention has a structure that is a member selected from: where q is a number between 0 and 1. R9 is halogen. Ra, Rb, Rc, Rd and Re are members independently selected from a selected member of H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl. In an exemplary embodiment, the compound in the pharmaceutical formulation is a member selected from In an exemplary embodiment, the compound has a structure that is a member selected from: In an exemplary embodiment, Ra, Rd, and Re are each members selected independently of: In an exemplary embodiment, Rb and Rc are members independently selected from H, methyl, In another exemplary embodiment, Rb is H and Rc is a member selected from H, methyl, O and O O In another exemplary embodiment, Rb is associated with the nitrogen to which they are attached, optionally linked to form a selected member of In an exemplary mode, Ra is a selected member of In an exemplary embodiment, Rb is a member selected from In an exemplary mode, Re is a selected member of In another exemplary embodiment, the pharmaceutical formulations described herein may form a hydrate with water, a solvate with an alcohol (e.g., methanol, ethanol, propanol); an adduct with an amino compound (for example, ammonia, methylamine, ethylamine); an adduct with an acid (for example, formic acid, acetic acid); complexes with ethanolamine, quinoline, amino acids and the like. In an exemplary embodiment, the pharmaceutical formulation comprises a compound having a structure according to formula (Ip): wherein Rx2 is a member selected from substituted or unsubstituted C1-C5 alkyl and substituted or unsubstituted C1-C5 heteroalkyl. R 2 and R x 2 are members independently selected from H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl. In an exemplary embodiment, the pharmaceutical formulation comprises a compound having a structure according to formula (Iq): where B is boron. Rx2 is a member selected from substituted or unsubstituted C1-C5 alkyl, and substituted or unsubstituted C1-C5 heteroalkyl. Ry2 and Rz2 are members independently selected from H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl. In another exemplary embodiment, at least one member selected from R 3 a, R 4 a, R 5 a, R 6 a, R a, R 8 a, R 9 a, R 10 a, R 1 a and R 12 a is a member selected from nitro, cyano and halogen. In an exemplary embodiment, the pharmaceutical formulation comprises a compound having a structure that is a member selected from the following formulas: In an exemplary embodiment, the pharmaceutical formulation comprises a compound having a formula according to formulas (Ib) - (le) wherein at least one member selected from R3a, R4a, R5a, R6a, R7a, R8a, R9a, R10a , Rlla and R12a is a member selected from nitro, cyano, fluoro, chloro, bromo and cyanophenoxy. In an exemplary embodiment, the pharmaceutical formulation comprises a compound having a structure that is a member selected from In an exemplary embodiment, the pharmaceutical formulation comprises a compound having a structure that is a member selected from In another exemplary embodiment, there is a condition that the pharmaceutical formulation can not comprise a structure according to the formula (Iaa): (Iaa) wherein R6b, R9b, R10b, Rllb and R12b have the same lists of substituents as those described for formulas (Ix) and (Iy) above. The pharmaceutical formulations of the invention may have a variety of forms adapted to select the route of administration. Those skilled in the art will recognize various synthetic methodologies that can be employed to prepare non-toxic pharmaceutical formulations incorporating the compounds described herein. Those skilled in the art will recognize a wide variety of non-toxic pharmaceutically acceptable solvents that can be used to prepare solvates of the compounds of the invention, such as water, ethanol, propylene glycol, mineral oil, vegetable oil and dimethyl sulfoxide (DMSO). The compositions of the invention can be administered orally, topically, parenterally, by inhalation or spray or rectally in single dose formulations containing conventional non-toxic pharmaceutically acceptable carriers, adjuvants and carriers. It is further understood that the best method of administration may be a combination of methods. Oral administration in the form of a pill, capsule, elixir, syrup, lozenge, troche or the like is particularly preferred. The term "parenteral" as used herein includes subcutaneous, intradermal, intravascular (e.g., intravenous), intramuscular, spinal, intrathecal injection, or similar injection or infusion techniques. Pharmaceutical formulations containing compounds of the invention are preferably in a form suitable for oral use, for example, as tablets, tablets, lozenges, aqueous or oily suspensions, dispersible powders or granules, emulsion, hard or soft capsules or syrups or elixirs . Compositions designed for oral use can be prepared according to any method known in the art for the manufacture of pharmaceutical formulations, and these compositions can contain one or more agents selected from the group consisting of sweetening agents, flavoring agents, coloring agents and preservatives. to thereby provide pharmaceutically elegant and palatable preparations. The tablets may contain the active ingredient in admixture with pharmaceutically acceptable non-toxic excipients which are suitable for the manufacture of tablets. These excipients may be, for example, inert diluents, such as calcium carbonate, sodium carbonate, lactose, calcium phosphate or sodium phosphate; granulation and disintegration agents, for example, corn starch or alginic acid; binding agents, for example starch, gelatin or acacia and lubricating agents, for example magnesium stearate, stearic acid or talc. The tablets may be uncoated or they may be coated by known techniques to delay disintegration and absorption in the gastrointestinal tract and thereby provide a prolonged action for a longer period. For example, a time delay material such as glyceryl monostearate and glyceryl distearate may be employed. Formulations for oral use may also be presented as hard gelatin capsules in which the active ingredient is mixed with an inert solid diluent, for example, calcium carbonate, calcium phosphate or kaolin, or as soft gelatin capsules in which the Active ingredient is mixed with water or a medium of oil, for example peanut oil, liquid paraffin or olive oil. The aqueous suspensions contain the active materials mixed with suitable excipients for the preparation of aqueous suspensions. These excipients are suspending agents, for example sodium carboxymethylcellulose, methylcellulose, hydroxypropylmethylcellulose, sodium alginate, polyvinylpyrrolidone, gum tragacanth and acacia gum and dispersing or wetting agents, which may be a naturally occurring phosphatide., for example, lecithin, or condensation products of an alkylene oxide with fatty acids, for example polyoxyethylene stearate, or condensation products of ethylene oxide with long-chain aliphatic alcohols, for example heptadecaethylene oxyketanol or oxide condensation products. ethylene with partial esters derived from fatty acids or a hexitol such as polyoxyethylene sorbitol monooleate, or condensation products of ethylene oxide with partial esters derived from fatty acids and hexitol anhydrides, for example polyethylenesorbitan monooleate. The aqueous suspensions may also contain one or more preservatives, for example ethyl or n-propyl p-hydroxybenzoate, one or more coloring agents, one or more flavoring agents and one or more sweetening agents, such as sucrose or saccharin. Oily suspensions may be formulated by suspending the active ingredients in a vegetable oil, for example arachis oil, olive oil, sesame oil or coconut oil, or in a mineral oil such as liquid paraffin. The oily suspensions may contain a thickening agent, for example, beeswax, hard paraffin or cetyl alcohol. Sweetening agents such as those shown above, and flavoring agents may be added to provide palatable oral preparations. These compositions can be preserved by the addition of an antioxidant such as ascorbic acid. Dispersible powders and granules suitable for the preparation of an aqueous suspension by the addition of water provide the active ingredient mixed with a dispersing or wetting agent, suspending agent and one or more preservatives. Suitable dispersing or wetting agents and suspending agents are exemplified by those already mentioned above. Additional excipients, for example sweetening, flavoring and coloring agents, may also be present. The pharmaceutical formulations of the invention may also be in the form of oil-in-water emulsions and water-in-oil emulsions. The oil phase can be a vegetable oil, for example olive oil or arachis oil, or a mineral oil, for example liquid paraffin or mixtures thereof. Suitable emulsifying agents can gums that occur naturally for example acacia gum or tragacanth gum; naturally occurring phosphatides, for example soybeans, lecithin and esters or partial ethers derived from fatty acids and hexitol; anhydrides, for example sorbitan monooleate and condensation products of the partial esters with ethylene oxide, for example polyoxyethylene sorbitan monooleate. The emulsions may also contain sweetening and flavoring agents. The syrups and elixirs can be formulated with sweetening agents, for example glycerol, propylene glycol, sorbitol or sucrose. These formulations may also contain a demulcent, a preservative and flavoring and coloring agents. The pharmaceutical formulations may be in the form of an injectable and sterile injectable aqueous or oleaginous suspension. This suspension can be formulated according to the known art using the suitable dispersing or wetting agents and suspending agents, which have been mentioned above. The sterile injectable preparation can also be a sterile injectable solution or suspension in a non-toxic parenterally-acceptable diluent or solvent, for example as a solution in 1,3-butanediol. Among the acceptable carriers and solvents that may be employed are water, Ringer's solution and isotonic sodium chloride solution. In addition, sterile and fixed oils are conventionally employed as a solvent or suspension medium. For this purpose any soft fixed oil can be employed including synthetic mono- or diglycerides. In addition, fatty acids such as oleic acid find use in the preparation of injectables. The composition of the invention can also be administered in the form of a suppository, for example, for rectal administration of the drug. These compositions can be prepared by mixing the drug with a suitable non-irritating excipient that is solid at ordinary temperatures but liquid at the rectal temperature and that therefore melts in the rectum to release the drug. These materials are cocoa butter and polyethylene glycols.

Alternatively, the compositions can be administered parenterally in a sterile medium. The drug, depending on the carrier and concentration used, can be either suspended or dissolved in the carrier. Suitably, adjuvants such as local anesthetics, preservatives and pH regulating agents can be dissolved in the carrier. For administration to non-human animals, the composition containing the therapeutic compound may be added to the animal's food or drinking water. Likewise, it will be convenient to formulate food for animals and water products to drink in such a way that the animal takes an adequate amount of compound in its diet. It will further be convenient to present the compound in a composition as a premix for addition to the food or drinking water. The composition can also be added as a food supplement or for human beverages. The dose levels in the order of about 5 mg to about 250 mg per kilogram of body weight per day and most preferably about 25 mg to about 150 mg per kilogram of body weight per day, are useful in the treatment of the indicated conditions above. The amount of active ingredient that can be combined with the carrier materials to produce a single dosage form will vary depending on the condition being treated and the particular mode of administration. The single dose forms will generally contain between about 1 mg to about 500 mg of an active ingredient. The dosage frequency may also vary depending on the compound used and the particular disease treated. However, for the treatment of most disorders, a dosing regimen of four times daily or less is preferred. However, it will be understood that the specific dose level for any particular patient will depend on a variety of factors including the activity of the specific compound employed, age, body weight, general health, sex, diet, time of administration, route of administration and Excretion rate, combination of drugs and the severity of the particular disease that is being submitted to therapy. Preferred compounds of the invention will have desirable pharmacological properties including, but not limited to, oral bioavailability, low toxicity, low serum protein binding, and desirable in vivo and in vivo half-lives. Penetration of the blood-brain barrier for compounds used to treat CNS disorders is necessary, although low brain levels of compounds used to treat peripheral disorders are commonly preferred. Assays can be used to predict these desirable pharmacological properties. The assays used to predict bioavailability include transport through monolayers of human intestinal cells, including monolayers of Caco-2 cells. The toxicity for cultured hepatocytes can be used to predict the toxicity of the compound. Penetration of the blood-brain barrier of a compound in humans can be predicted from the brain levels of laboratory animals that receive the compound intravenously. Serum protein binding can be predicted from albumin binding assays. These trials are described in a review by Oravcova, et al. (Journal of Chromatography B (1996) volume 677, pages 1-27). The half-life of the compound is inversely proportional to the frequency of dosage of a compound. Average lives in Vi tro compounds can be predicted from microsomal half-life assays such as those described by Kuhnz and Gieschen (Drug Metabolism and Disposition, (1998) volume 26, pages 1120-1227). The amount of the composition required to be used in the treatment will vary not only with the particular compound selected but also with the route of administration, the nature of the condition being treated and the age and condition of the patient and will ultimately be at the discretion of the patient. medical or clinical care.

In an exemplary embodiment, the pharmaceutical formulation excipient comprises ethanol and the pharmaceutical formulation is 1,3-dihydro-5-fluoro-l-hydroxy-2, 1-benzoxazole. In another exemplary embodiment, the excipient for the pharmaceutical formulation comprises propylene glycol and the compound of the pharmaceutical formulation is 1,3-dihydro-5-fluoro-l-hydroxy-2, 1-benzoxazole. In an exemplary embodiment, the pharmaceutical formulation comprises: propylene glycol: ethanol about 1: 4, with 1:10 p / volume of 1,3-dihydro-5-fluoro-l-hydroxy-2, 1-benzoxazole. In an exemplary embodiment the pharmaceutical formulation comprises: about 70% ethanol; about 20% monobutyl ester of poly (vinyl methyl ether-alt-maleic acid); about 10% of 1,3-dihydro-5-fluoro-l-hydroxy-2, 1-benzoxazole. In an exemplary embodiment the pharmaceutical formulation comprises: about 56% ethanol; around 14% water; about 15% poly (2-hydroxyethyl) methacrylate; about 5% di-butyl sebacate; about 10% of 1,3-dihydro-5-fluoro-l-hydroxy-2, 1-benzoxazole. In an exemplary embodiment the pharmaceutical formulation comprises: about 55% ethanol; about 15% ethyl acetate; about 15% polyvinyl acetate; about 5% dibutyl sebacate; about 10% of 1,3-dihydro-5-fluoro-l-hydroxy-2, 1-benzoxazole. In another exemplary embodiment, 1,3-dihydro-5-fluoro-1-hydroxy-2, 1-benzoxazole is present in a pharmaceutical formulation at a concentration that is a selected member of 1%, 2.5%, 5%, 7.5 %, 10% and 15% p / v. In another exemplary embodiment, the pharmaceutical formulation is a lacquer. In an exemplary embodiment, the excipient of the pharmaceutical formulation comprises ethanol and the compound of the pharmaceutical formulation is 5- (4-cyanophenoxy) -1,3-dihydro-l-hydroxy-2, 1-benzoxazole. In another exemplary embodiment, the excipient of the pharmaceutical formulation comprises propylene glycol and the compound of the pharmaceutical formulation is 5- (4-cyanophenoxy) -1,3-dihydro-l-hydroxy-2, 1-benzoxazole. In an exemplary embodiment, the pharmaceutical formulation comprises about 20% propylene glycol; about 70% ethanol; about 10% of 5- (4-cyanophenoxy) -1,3-dihydro-l-hydroxy-2, 1-benzoxazole. In an exemplary embodiment the pharmaceutical formulation comprises: about 70% ethanol; about 20% poly (vinyl methyl ether-alt-maleic acid) monobutyl ester; about 10% of 5- (4-cyanophenoxy) -1,3-dihydro-l-hydroxy-2, 1-benzoxazole. In an exemplary embodiment the pharmaceutical formulation comprises: about 56% ethanol; about 14% water; about 15% poly (2-hydroxyethyl) methacrylate; about 5% dibutyl sebacate; about 10% of 5- (4-cyanophenoxy) -1,3-dihydro-l-hydroxy-2, 1-benzoxazole. In an exemplary embodiment the pharmaceutical formulation comprises: about 55% by weight of ethanol; about 15% ethyl acetate; about 15% polyvinyl acetate; about 5% dibutyl sebacate; about 10% of 5- (4-cyanophenoxy) -1,3-dihydro-l-hydroxy-2, 1-benzoxazole. In another exemplary embodiment, 5- (4-cyanophenoxy) -1,3-dihydro-1-hydroxy-2, 1-benzoxazole is present in a pharmaceutical formulation at a concentration which is a selected member of 1%, 2.5%, 5%, 7.5%, 10% and 15% p / v. In another exemplary embodiment, the pharmaceutical formulation is a lacquer. In an exemplary embodiment, the excipient of the pharmaceutical formulation comprises ethanol and the compound of the pharmaceutical formulation is a compound described herein. In another exemplary embodiment, the excipient of the pharmaceutical formulation comprises propylene glycol and the compound of the pharmaceutical formulation is a compound described herein. In an exemplary embodiment the pharmaceutical formulation comprises: about 20% propylene glycol; around 70% ethanol; about 10% of a compound described herein. In an exemplary embodiment the pharmaceutical formulation comprises: approximately 70% ethanol; about 20% poly (vinyl methyl ether-alt-maleic acid) monobutyl ester; about 10% of a compound described herein. In an exemplary embodiment the pharmaceutical formulation comprises: about 56% ethanol; around 14% water; about 15% poly (2-hydroxyethyl) methacrylate; about 5% dibutyl sebacate; about 10% of a compound described herein. In an exemplary embodiment the pharmaceutical formulation comprises: about 55% ethanol; about 15% ethyl acetate; about 15% polyvinyl acetate; about 5% dibutyl sebacate; about 10% of a compound described herein. In another exemplary embodiment, a compound described herein is present in a pharmaceutical formulation at a concentration that is a member selected from 1%, 2.5%, 5%, 7.5%, 10% and 15% w / v. In another exemplary embodiment, the pharmaceutical formulation is a lacquer. Vile. a) Topical Formulations In a preferred embodiment, the methods of the invention can be used employed through the topical application of the compounds described herein. The compositions of the present invention comprise fluid or semi-solid carriers which may include but are not limited to polymers, thickeners, pH regulators, neutralizers, chelating agents, preservatives, surfactants or emulsifiers, antioxidants, waxes or oils, emollients, sunscreens and a solvent or system of mixed solvents. The solvent or system of mixed solvents is important for the formulation since it is mainly responsible for the dissolution of the drug. The best mixed solvent or solvent systems are also capable of maintaining clinically relevant levels of the drug in solution despite the addition of a deficient solvent to the formulation. Topical compositions useful in the present invention can be made in a wide variety of product types. These include, but are not limited to, lotions, creams, gels, bars, sprays, ointments, pastes, foams, moueeee and cleansers. These product types can comprise various types of carrier systems including, but not limited to, particles, nanoparticles and liposomes. If desired, disintegrating agents may be added, such as the interlaced polyvinylpyrrolidone, agar or alginic acid or a salt thereof such as sodium alginate. The techniques for formulation and administration can be found in Remington: The Science and Practice of Pharmacy, cited above. The formulation can be selected to maximize delivery to a desired target site in the body. Lotions, which are preparations to be applied to the skin, nail, hair, claw or hoof surface without friction, are typically liquid or semi-liquid preparations in which finely divided, waxy or liquid solids are dispersed. The lotions will typically contain suspending agents to produce better dispersions as well as compounds useful for locating and maintaining the active agent in contact with the skin, nail, hair, claw or hoof, for example, methylcellulose, sodium carboxymethylcellulose or the like. The creams containing the active agent for delivery according to the present invention are viscous liquid or semi-solid emulsions, either oil-in-water or water-in-oil. The cream bases are washable with water, and contain an oil phase, an emulsifier and an aqueous phase. The oil phase is generally comprised of petrolatum or a fatty alcohol, such as cetyl or stearyl alcohol. The aqueous phase usually, although not necessarily, exceeds the oil phase by volume, and generally contains a humectant. The emulsifier in a cream formulation, as explained in Remington: The Science and Practice of Pharmacy, cited above, is generally a non-ionic surfactant, anionic, cationic or amphoteric. Gel formulations can also be used in connection with the present invention. As will be apparent by those who work in the field of topical drug formulation, the gels are semi-solid. Individual phase gels contain organic macromolecules distributed substantially uniformly along the carrier liquid, which is typically aqueous, but can also be a solvent or mixture of solvents. Ointments, which are semi-solid preparations, are typically based on petrolatum or other petroleum derivatives. As will be appreciated by one of ordinary skill in the art, the specific ointment base to be used is one that provides the optimum supply of the active agent selected for a given formulation and, preferably, that provides other desired characteristics as well, for example, emolliency. or similar. As with other carriers or carriers, an ointment base must be inert, stable, non-irritating and non-sensitizing. As explained in Remington: The Science and Practice of Pharmacy, 19B ed. (Easton, Pa .: Mack Publishing Co., 1995), on pages 1399-1404, ointment bases can be grouped into four classes: oil bases; emulsifiable bases; emulsion bases and water-soluble bases. Oleaginous ointment bases include, for example, vegetable oils, fats obtained from animals and semisolid hydrocarbons obtained from petroleum. Emulsifiable ointment bases, also known as absorbent ointment bases, contain very little or no water and include, for example, hydroxystearin sulfate, anhydrous lanolin and hydrophilic petrolatum. The emulsion ointment bases are either water-in-oil (W / O) or oil-in-water (O / W) emulsions and include, for example, cetyl alcohol, glyceryl monostearate, lanolin and stearic acid. Preferred water-soluble ointment bases are prepared from polyethylene glycols of variable molecular weight; again, reference may be made to Remington: The Science and Practice of Pharmacy, cited above, for additional information. Useful formulations of the invention also encompass sprays. The sprays generally provide the active agent in an aqueous and / or alcoholic solution that can be aerosolized on the skin, nail, hair, claw or hoof for its supply. These sprays include those formulated to provide the concentration of the active agent solution at the site of administration after delivery, for example, the spray solution may be composed primarily of alcohol or other similar volatile liquid in which the drug or active agent can be dissolved. After its supply to the skin, nail, hair, claw or hoof, the carrier evaporates leaving concentrated active agent in the administration site. Topical pharmaceutical compositions may also comprise suitable solid phase or gel carriers. Examples of these carriers include but are not limited to calcium carbonate, calcium phosphate, various sugars, starches, cellulose derivatives, gelatin and polymers such as polyethylene glycols.

Topical pharmaceutical compositions may also comprise a suitable emulsifier which relates to an agent that increases or facilitates the mixing and suspension of oil in water or water in oil. The emulsifying agent used herein may consist of a single emulsifying agent or may be a nonionic, anionic, cationic or amphoteric surfactant or mixture of two or more of these surfactants; it is preferred to use nonionic or anionic emulsifiers herein. These surfactants are described in "McCutcheon's Detergent and Emulsifiers," North American Edition, 1980 Annual Publisher by the McCutcheon Division, MC Publishing Company, 175 Rock Road, Glen Rock, N.J. 07452, E.U.A. It is preferred to use in the present high molecular weight alcohols such as cetearyl alcohol, cetyl alcohol, stearyl alcohol, emulsifying wax, glyceryl monostearate. Other examples are ethylene glycol distearate, sorbitol tristerate, propylene glycol monostearate, sorbitan monooleate, sorbitan monostearate (SPAN 60), diethylene glycol monolaurate, sorbitan monopalmitate, sucrose dioleate, sucrose stearate (CRODESTA F-160), ether polyoxyethylene lauryl ether (BRIJ 30), polyoxyethylene (2) stearyl ether (BRIJ 72), polyoxyethylene (21) stearyl ether (BRIJ 721), polyoxyethylene monostearate (Myrj 45), polyoxyethylene sorbitan monostearate (TWEEN 60), polyoxyethylene sorbitan monooleate (TWEEN 80) ), polyoxyethylene sorbitan monolaurate (TWEEN 20) and sodium oleate. Cholesterol and cholesterol derivatives can also be used in externally used emulsions and promote w / o emulsions. Especially suitable nonionic emulsifying agents are those with hydrophilic-lipophilic equilibria (HLB) of about 3 to 6 for system w / o and 8 to 18 for system o / w as determined by the method described by Paul L. Lindner in "Emulsions and Emulsion ", edited by Kenneth Lissant, published by Dekker, New York, NY, 1974, pages 188-190. It is more preferred to use in the present one or more nonionic surfactants that produce a system having an HLB of about 8 to about 18. Examples of these nonionic emulsifiers include but are not limited to "BRIJ 72", the trade name for a polyoxyethylene (2) stearyl ether having an HLB of 4.9; "BRIJ 721", the trade name of a polyoxyethylene (21) stearyl ether having an HLB of 15.5, "Brij 30", the commercial name of polyoxyethylene lauryl ether having an HLB of 9.7; "Polawax", the trade name of an emulsifying wax that has an HLB of 8.0; "Span 60", the commercial name of sorbitan monostearate having an HLB of 4.7; "Crodesta F-160", the commercial name of sucrose stearate "having an HLB of 14.5, all of these materials are available from Ruger Chemicals Inc., Croda, ICI Americas, Inc., Spectrum Chemicals and BASF. of the present invention contain at least one emulsifying agent, each emulsifying agent is present in an amount of from about 0.5 to about 2.5% by weight, preferably 0.5 to 2.0%, most preferably 1.0% or 1.8% .Preferably the emulsifying agent comprises a mixture of steareth 21 (at about 1.8%) and steareth 2 (at about 1.0%). Topical pharmaceutical compositions may also comprise suitable emollients.The emollients are materials used for the prevention or relief of dryness, as well as for protecting the skin, nail, hair, claw or hoof Useful emollients include, but are not limited to, cetyl alcohol, isopropyl myristate, stearyl alcohol and the like. it knows a wide variety of suitable emollients and can be used herein. See, for example, Sagarin, Cosmetics, Science and Technology, 2nd edition, vol. 1, pages 32-43 (1972) and patent of E.U.A. No. 4,919,934 to Deckner et al., Issued April 24, 1990, both of which are hereby incorporated by reference in their entirety. These materials are available from Ruger Chemical Co, (Irvington, J).

When the topical formulations of the present invention contain at least one emollient, each emollient is present in an amount of from about 0.1 to 15%, preferably 0.1 to about 3.0, most preferably 0.5, 1.0 or 2.5% by weight. Preferably the emollient is a mixture of cetyl alcohol, isopropyl myristate and stearyl alcohol in a 1/5/2 ratio. The emollient may also include a mixture of cetyl alcohol and stearyl alcohol in a 1/2 ratio. Topical pharmaceutical compositions may also comprise suitable antioxidants, a substance known to inhibit oxidation. Suitable antioxidants for use in accordance with the present invention include, but are not limited to, butylated hydroxytoluene, ascorbic acid, sodium ascorbate, calcium ascorbate, ascorbic palmitate, butylated hydroxyanisole, 2,4,5-trihydroxybutyrophenone, 4-hydroxymethyl -2,6-di-er-butylphenol, erythorbic acid, guayac gum, propyl gallate, thiodipropionic acid, dilauryl thiodipropionate, tert-butylhydroquinone and tocopherols such as vitamin E, and the like, including pharmaceutically acceptable salts and esters of these compounds . Preferably, the antioxidant is butylated hydroxytoluene, butylated hydroxyanisole, propylgalate, ascorbic acid, pharmaceutically acceptable salts or esters thereof, or mixtures thereof. Most preferably, the antioxidant is butylated hydroxytoluene. These materials are available from Ruger Chemical Co, (Irvington, NJ). When the topical formulations of the present invention contain at least one antioxidant, the total amount of antioxidant present is about 0.001 to 0.5% by weight, preferably 0.05 to about 0.5% by weight, most preferably 0.1%. Topical pharmaceutical compositions may also comprise suitable preservatives. The preservatives are compounds added to a pharmaceutical formulation to act as an antimicrobial agent. Among the preservatives known in the art as effective and acceptable in parenteral formulations are benzalkonium chloride, benzethonium, chlorhexidine, phenol, m-cresol, benzyl alcohol, methylparaben, propylparaben, chlorobutanol, o-cresol, p-cresol, chlorocresol, phenylmercuric nitrate. , thimerosal, benzoic acid and various mixtures thereof. See, for example, Wallhausser, K.-H., Develop. Biol. Standard, 24: 9-28 (1974) (S. Krager, Basel). Preferably, the preservative is selected from methylparaben, propylparaben and mixtures thereof. These materials are available from Inolex Chemical Co (Philadelphia, PA) or Spectrum Chemicals. When the topical formulations of the present invention contain at least one preservative, the total amount of preservative present is from about 0.01 to about 0.5% by weight, preferably about 0.1 to 0.5%, most preferably about 0.03 to about 0.15. Preferably the preservative is a mixture of methylparaben and propylparaben in a 5/1 ratio. When alcohol is used as a preservative, the amount is usually 15 to 20%. Topical pharmaceutical compositions may also comprise chelating agents suitable for forming complexes with metal cations that do not cross a lipid bilayer. Examples of suitable chelating agents include ethylenediaminetetraacetic acid (EDTA), ethylene glycol bis (beta-aminoethyl ether) -N, N, N ', N' -tetraacetic acid (EGTA) and 8-amino-2- [(2-amino -5-methylphenoxy) methyl] -6-methoxyquinoline-N, N, NXN'-tetraacetic, tetrapotassium salt (QUIN-2). Preferably the chelating agents are EDTA and citric acid. These materials are available from Spectrum Chemicals. When the topical formulations of the present invention contain at least one chelating agent, the total amount of chelating agent present is from about 0.005% to 2.0% by weight, preferably about 0.05% to about 0.5% by weight, most preferably about of 0.1% by weight. Topical pharmaceutical compositions may also comprise suitable neutralizing agents used to adjust the pH of the formulation to within a pharmaceutically acceptable scale. Examples of neutralizing agents include but are not limited to trolamine, tromethamine, sodium hydroxide, hydrochloric acid, citric acid and acetic acid. These materials are available from Spectrum Chemicals (Gardena, CA). When the topical formulations of the present invention contain at least one neutralizing agent, the total amount of neutralizing agent present is from about 0.1 wt% to about 10 wt%, preferably 0.1 wt% to about 5.0 wt% and most preferably at about 1.0% by weight. The neutralizing agent is generally added in any amount that is required to bring the formulation to the desired pH. Topical pharmaceutical compositions may also comprise suitable viscosity improving agents. These components are diffusible compounds capable of increasing the viscosity of a solution containing polymer through the interaction of the agent with the polymer. CARBOPOL ULTREZ 10 can be used as a viscosity improving agent. These materials are available from Ninth Chemicals, Cleveland, OH. When the topical formulations of the present invention contain at least one viscosity improving agent, the total amount of viscosity improving agent present is from about 0.25% to about 0.5% by weight, preferably about 0.25% to about 1.0. % by weight and most preferably at about 0.4% to about 0.6% by weight. Topical pharmaceutical compositions may also comprise suitable nail penetration enhancers. Examples of nail penetration enhancers include mercaptan, sulfite and bisulfite compounds, keratolytic agents and surfactants. Nail penetration enhancers suitable for use in the invention are described in greater detail in Malhotra et al. , J. Pharm. Sci. , 91: 2, 312-323 (2002), which is hereby incorporated by reference in its entirety. Topical pharmaceutical compositions may also comprise one or more suitable solvents. The ability of any solid substance (solute) to dissolve in any liquid substance (solvent) depends on the physical properties of the solute and the solvent. When solutes and solvents have similar physical properties the solubility of the solute in the solvent will be greatest. This gives rise to the traditional understanding that "similar dissolves similar". Solvents can be characterized at one extreme as nonpolar lipophilic oils, while at the other extreme as polar hydrophilic solvents. Oily solvents dissolve other non-polar substances through Van der Wals interactions while water and other hydrophilic solvents dissolve polar substances by ionic, dipolar, or hydrogen bonding interactions. All solvents can be listed along a continuum from the least polar, that is, hydrocarbons such as decane, to the more polar solvent being water. A solute will give its greater solubility in solvents that have equivalent polarity. Thus, for drugs that have minimal solubility in water, less polar solvents will provide improved solubility with the solvent having a polarity almost equivalent to that of the solute providing maximum solubility. Most drugs have intermediate polarity, and thus experience maximum solubility in solvents such as propylene glycol or ethanol, which are significantly less polar than water. If the drug has greater solubility in propylene glycol (for example 8% (w / w)) than in water (for example 0.1% (w / w)), then the addition of water to propylene glycol should reduce the maximum amount of drug solubility for the mixture of solvents in comparison with pure propylene glycol. The addition of a deficient solvent to an excellent solvent will reduce the maximum solubility for the mixture compared to the maximum solubility in the excellent solvent. When the compounds are incorporated into topical formulations the concentration of active ingredient in the formulation can be limited by the solubility of the active ingredient in the selected solvent and / or carrier. Non-lipophilic drugs typically exhibit very low solubility in pharmaceutically acceptable solvents and / or carriers. For example, the solubility of some compounds in the invention in water is less than 0.00025% w / w. The solubility of the same compounds in the invention may be less than about 2% w / w either in propylene glycol or isopropyl myristate. In one embodiment of the present invention, diethylene glycol monoethyl ether (DGME) is the solvent used to dissolve the compounds of the invention. It is believed that the compounds of the invention useful in the present formulation have a solubility of about 10 wt% w / w to about 25 wt% in DGME. In another embodiment a DGME water cosolvent system is used to dissolve the compounds of the invention. The solvent capacity of DGME drops when water is added; however, the DGME / water cosolvent system can be designed to maintain the desired concentration from about 0.1% to about 5% w / w active ingredient. Preferably the active ingredient is present in an amount of from about 0.5% to about 3% w / w, and most preferably about 1% w / w, in the topical formulations applied as is. Since DGME is less volatile than water, upon evaporation of the topical formulation after its application, the active agent becomes more soluble in the cream formulation. This increased solubility reduces the likelihood of reduced bioavailability caused by the drug when precipitated "on the surface of the skin, nail, hair, claw or hoof Liquid forms, such as lotions suitable for topical administration or suitable for cosmetic application, may include a suitable aqueous or non-aqueous carrier with pH regulators, suspending and dispensing agents, thickeners, penetration enhancers and the like Solid forms such as creams or pastes or the like may include, for example, any of the following ingredients, water, oil , alcohol or fat as a substrate with surfactant, polymers such as polyethylene glycol, thickeners, solids and the like Liquid or solid formulations may include increased delivery technologies such as liposomes, microsomes, microsponges and the like. using a prolonged release system da, such as semipermeable matrices of solid hydrophobic polymers containing the therapeutic agent. Various prolonged release materials have been established and are well known to those skilled in the art. Topical treatment regimens according to the practice of this invention comprise applying the composition directly to the skin, nail, hair, claw or hoof at the site of application, one to several times a day. The formulations of the present invention can be used to treat, reduce or prevent conditions or symptoms associated with bacterial infections, acne, inflammation and the like. In an exemplary embodiment, the pharmaceutical formulation includes a simple solution. In an exemplary embodiment, the simple solution includes an alcohol. In an exemplary embodiment, the simple solution includes alcohol and water. In an exemplary embodiment, the alcohol is ethanol, ethylene glycol, propanol, polypropylene glycol, isopropanol or butanol. In another exemplary embodiment, the simple solution is a member selected from about 10% polypropylene glycol and about 90% ethanol; about 20% polypropylene glycol and about 80% ethanol; about 30% polypropylene glycol and about 70% ethanol; about 40% polypropylene glycol and about 60% ethanol; about 50% polypropylene glycol and about 50% ethanol; about 60% polypropylene glycol and about 40% ethanol; about 70% polypropylene glycol and about 30% ethanol; about 80% polypropylene glycol and about 20% ethanol; about 90% polypropylene glycol and about 10% ethanol. In an exemplary embodiment, the pharmaceutical formulation is a lacquer. Please see Remington, cited above, for more information on lacquer production. In an exemplary embodiment, the compound is present in the pharmaceutical formulation at a concentration of about 0.5% to about 15%. In an exemplary embodiment, the compound is present in the pharmaceutical formulation at a concentration of from about 0.1% to about 12.5%. In an exemplary embodiment, the compound is present in the pharmaceutical formulation at a concentration of from about 1% to about 10%. In an exemplary embodiment, the compound is present in the pharmaceutical formulation at a concentration of from about 1% to about 5%. In an exemplary mode, the compound is present in the pharmaceutical formulation at a concentration of about 0.5% to about 7.5%. In an exemplary embodiment, the compound is present in the pharmaceutical formulation at a concentration of from about 5% to about 7.5%. In an exemplary embodiment, the compound is present in the pharmaceutical formulation at a concentration of from about 2% to about 8%. In an exemplary embodiment, the compound is present in the pharmaceutical formulation at a concentration of from about 4% to about 9%. VII. b) Additional Active Agents The following are examples of the cosmetic and pharmaceutical agents that can be added to the topical pharmaceutical formulations of the present invention.

The following agents are known compounds and are readily available commercially. Anti-inflammatory agents include, but are not limited to, bisabolol, mentolate, dapsone, aloe, hydrocortisone and the like. Vitamins include, but are not limited to, vitamin B, vitamin E, vitamin A, vitamin D and the like and vitamin derivatives such as tazarotene, calcipotriene, tretinoin, adapalene and the like. Anti-aging agents include, but are not limited to, niacinamide, retinol and retinoid derivatives, AHA, ascorbic acid, lipoic acid, coenzyme Q , beta hydroxy acids, salicylic acid, copper binding peptides, dimethylaminoethyl (DAEA), and the like. Sun filters and / or sunburn relief agents include, but are not limited to, PABA, jojoba, aloe, padimato-O, methoxycinnamates, proxamine HCl, lidocaine, and the like. Tanning agents without sun include, but are not limited to, dihydroxyacetone (DHA).

Agents for treating psoriasis and / or agents for treating acne include, but are not limited to, salicylic acid, benzoyl peroxide, carbon alkyltrán, selenium sulfide, zinc oxide, pyrithione (zinc and / or sodium), tazarotene, calcipotriene, tretinoin, adapalene and the like. Agents that are effective in controlling or modifying keratinization, including without limitation: tretinoin, tazarotene and adapalene. Compositions comprising a compound / active agent of the invention, and optionally at least one of these additional agents, are to be administered topically. In a primary application, this leads to the compounds of the invention and any other active agent that functions after and treats the skin, nail, hair, claw or hoof. Alternatively, any of the active agents applied topically can also be delivered systemically by transdermal routes. In these compositions an additional cosmetic or pharmaceutically active agent, such as an anti-inflammatory agent, vitamin, anti-aging agent, sunscreen and / or acne treatment agent, for example, is usually a minor component (of about 0.001% a about 20% by weight or preferably about 0.01% to about 10% by weight) with the remainder being different carriers or carriers and processing aids useful in forming the desired dosage form. VII. c) Tests Preferred compounds for use in the present topical formulations will have certain pharmacological properties. These properties include, but are not limited to, low toxicity, low binding to serum proteins and desirable in vivo and in vivo half-lives. Assays can be used to predict these desirable pharmacological properties. The assays used to predict bioavailability include transport through monolayers of human intestinal cells, including monolayers of Caco-2 cells. Serum protein binding can be predicted from albumin binding assays. These trials are described in a review by Oravcova et al. (1996, J. Chromat, B677: 1-27). The half-life of the compound is inversely proportional to the frequency of dosage of a compound. Half-lives in compounds can be produced from microsomal half-life assays such as those described by Kuhnz and Gleschen (Drug Metabolism and Disposition, (1998) volume 26, pages 1120-1127). The toxicity and therapeutic efficacy of these compounds can be determined by standard pharmaceutical procedures in cell cultures or experimental animals, for example, to determine the LD50 (the lethal dose for 50% of the population) and the ED50 (the therapeutically effective dose in 50%). % of the population). The dose ratio between toxic and therapeutic effects is the therapeutic index and can be expressed as the ratio between LD50 and ED50. Compounds that exhibit high therapeutic indices are preferred. The data obtained from these cell culture assays and animal studies can be used to formulate a range of dosages for use in humans. The dosage of these compounds is preferably based on a scale of circulating concentrations that include the ED5o with little or no toxicity. The dosage may vary within this scale depending on the dosage form employed and the route of administration used. The exact formulation, route of administration and doses can be selected by the individual physician in view of the patient's condition. (See, for example, Fingí et al., 1975, in "The Pharmacological Basis of Therapeutics," C. 1, p.1). VII. d) Administration For any compound used in the method of the invention, the therapeutically effective dose can be calculated initially from cell culture assays, such as those described herein. For example, a dose can be formulated in animal models to achieve a circulating concentration scale that includes the EC50 (effective dose for 50% improvement) as determined in cell culture, i.e. the concentration of the test compound that achieves a mean maximum inhibition of bacterial cell growth. This information can be used to more accurately determine useful doses in humans. In general, the compounds prepared by the methods, and from the intermediates, described herein will be administered in a therapeutically or cosmetically effective amount by any accepted mode of administration or for agents serving similar purposes. However, it will be understood that the specific dose level for any particular patient will depend on a variety of factors including the activity of the specific compound employed, age, body weight, general health, sex, diet, time of administration, route of administration and speed of excretion, combination of drugs, the severity of the particular disease that is undergoing therapy and the judgment of the attending physician. The drug can be administered once to twice a day, or up to 3 or 4 times a day. The amount and dosage range can be adjusted individually to provide plasma levels of the active portion that are sufficient to maintain inhibitory effects of bacterial cell growth. The usual patient doses for systemic administration vary from 0.1 to 1000 mg / day, preferably, 1-500 mg / day, most preferably 10-200 mg / day, still more preferably 100-200 mg / day. Said in terms of patient's body surface areas, the usual doses vary from 50-91 mg / m2 / day. The amount of the compound in a formulation can vary within the full scale employed by those skilled in the art. Typically, the formulation will contain, on a weight percent basis (% p), about 0.01-10% by weight of the drug based on the total formulation, the remainder being one or more suitable pharmaceutical excipients. Preferably, the compound is present at a level of about 0.1-0.3% by weight, most preferably about 1.0% by weight. The invention is further illustrated by the following examples. The examples are not designed to define or limit the scope of the invention. EXAMPLES Proton NMR are recorded in Varian spectrometer AS 300 and chemical changes are reported as 6 (ppm) downfield of tetramethylsilane. Mass spectra were determined in Micromass Quattro IL Example 1 Preparation of 3 from 1 1.1 Reduction of carboxylic acid To a solution of 1 (23.3 mmol) in anhydrous THF (70 mL) under nitrogen was added dropwise a solution of THF BH3 (1.0 M, 55 mL, 55 mmol) at 0 ° C and the reaction mixture was stirred overnight at room temperature. The mixture was then cooled again with ice bath and MeOH (20 mL) was added dropwise to remove excess BH3. The resulting mixture was stirred until no bubbles were released and then 10% NaOH (10 mL) was added. The mixture was concentrated and the residue was mixed with water (200 mL) and extracted with EtOAc. The rotary evaporation residue was purified by flash column chromatography on silica gel to give 20.7 mmoles of 3. 1.2 Replenished The exemplary compounds of structure 3 prepared by the method described above are provided below. 1. 2. 2-Bromo-5-chlorobenzyl alcohol XH NMR (300 MHz, DMSO-d6): d 7.57 (d, J = 8.7 Hz, 1H), 7.50-7.49 (m, 1H), 7.28-7.24 (m, 1H), 5.59 (t, J = 6.0 Hz, 1H) and 4.46 (d, J = 6.0 Hz, 2H) ppm. 1.2.b Alcohol 2-Bromo-5-methoxybenzyl XH NMR (300 MHz, DMSO-d6): d 7.42 (d, J = 8.7 Hz, 1H), 7. 09 (d, J = 2.4 Hz, 1H), 6.77 (dd, J? = 3 Hz, J2 = 3 Hz, 1H), . 43 (t, J = 5.7 Hz, 1H), 4.44 (d, J = 5.1 Hz, 2H), 3.76 (s, 3H).

Example 2 Preparation of 3 from 2 2.1. Reduction of Aldehyde To a solution of 2 (Z = H, 10.7 mmol) in methanol (30 mL) was added sodium borohydride (5.40 mol), and the mixture was stirred at room temperature for 1 h. Water was added thereto, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure to provide 9.9 mmoles of 3. 2.2 Results Exemplary compounds of structure 3 prepared by the above method are provided below. 2.2.a Alcohol 2-bromo-5- (4-cyanofenoxi) benzyl hl-NMR (300 MHz, CDCl 3) d (ppm) 2.00 (br s, 1H), 4.75 (s, 2H), 6.88 (dd, J = 8.5, 2.9 Hz, 1H), 7.02 (d, J = 8.8 Hz, 1H), 7.26 (d, J = 2.6 Hz, 1H), 7.56 (d, J 8.5 Hz, 1H), 7.62 (d, J = 8.8 Hz, 2H). 2.2.b Alcohol 2 -Bromo-4- (4-cyano phenoxy) benzyl XH NMR (300 MHz, DMSO-d6): d 7.83 (d, 2H), 7.58 (d, 1H), 7.39 (d, 1H), 7.18 (dd, 1H), 7.11 (d, 2H), 5.48 (t, 1H) and 4.50 (d, 2H) ppm. 2.2.c 5- (4-cyano phenoxy) -1-indanol P.F..50-53 ° C. MS (ESI +): m / z = 252 (M + 1). HPLC: 99.7% purity at 254 nm and 99.0% at 220 nm. X H NMR (300 MHz, DMSO-de): d 7.80 (d, 2H), 7.37 (d, 1H), 7.04 (d, 2H), 6.98-6.93 (m, 2H), 5.27 (d, 1H), 5.03 (q, 1H), 2.95-2.85 (m, 1H), 2.75-2.64 (m, 1H), 2.39-2.29 (m, 1H) and 1.85-1.74 (m, 1H) ppm. 2.2.d 2-Bromo-5- (tert-butyldimethylethyloxy) benzyl alcohol 1 H-NMR (300 MHz, CDC13) d (ppm) 0.20 (s, 61-1), 0.98 (s, 9H), 4.67 (br s, l H), 6.65 (dd, J = 8.2, 2.6 Hz, 1H), 6.98 (d, J = 2.9 Hz, 1H), 7.36 (d, J = 8.8 Hz, 1H). Additional examples of compounds that can be produced by this method include 2-bromo-4- (3-cyano-enoxy) benzyl alcohol; 2-bromo-4- (4-chlorofenoxyl) benzyl alcohol; 2-bromo-4-phenoxybenzyl alcohol; 2-bromo-5- (3,4-dicyanofenoxyl) benzyl alcohol; 2- (2-bromo-5-fluorophenyl) ethyl alcohol; 2-bromo-5-fluorobenzyl alcohol; and l-brcmo-2-naphthalenemethanol. Example 3 Preparation of 4 from 3 3.1 Protective Alkylation Compound 3 (20.7 mmol) was dissolved in CH2C12 (150 mL) and cooled to 0 ° C in an ice bath. To this solution under nitrogen were added in sequence N, N-di-isopropyl ethyl amine (5.4 mL, 31.02 mmol, 1.5 eq.) And chloromethyl methyl ether (2 mL, 25.85 mmol, 1.25 eq). The reaction mixture was stirred overnight at room temperature and washed with water saturated with NaHCO 3 and then water saturated with NaCl. The residue after rotary evaporation was purified by flash column chromatography on silica gel to give 17.6 mmoles of 4. 3.2. Replenishing Exemplary compounds of structure 4 prepared by the above method are provided below. 3.2.a 2-Bromo-5-chloro-l- (methoxymethoxymethyl) benzene XH NMR (300 MHz, DMSO-d6): d 7.63 (d, J = 8.7 Hz, 1H), 7.50 (dd, J = 2.4 &0.6 Hz, 1H), 7.32 (dd, J = 8.4 and 2.4 Hz, 1H), 4.71 (s, 2H), 4.53 (s, 2H) and 3.30 (s, 3H) ppm. 3.2.b 2-Bromo-5-fluoro-l - [1- (methoxymethoxy) ethyl] benzene XH-NMR (300.058 MHz, CDC13) d ppm 1.43 (d, J = € .5 Hz, 3H), 3.38 (s, 3H), 4.55 (d, J = 6.5 Hz, 1H), 4.63 (d, J = 6.5 Hz, 1H), 5.07 (q, J = 6.5 Hz, 1H), 6.85 (, 1H) ), 7.25 (dd, J = 9.7, 2.6 Hz, 1H), 7.46 (dd, J = 8.8, 5.3 Hz, 1H). 3.2.C 2-Bromo-5-fluoro-l- [2- (methoxymethoxy) ethyl] benzene XH-NMR (300.058 MHz, CDCl3) d mp 3.04 (t, J = 6.7 Hz, 2H), 3.31 (s, 3H), 3.77 (t, J = 6.7 Hz, 2H), 4.62 (s, 2H), 6.82 (td, J = 8.2, 3.2 Hz, 1H), 7.04 (dd, J = 9.4 , 2.9 Hz, 1H), 7.48 (dd, J '- = 8.8, 5.3 Hz, 1H). 3. 2. d 2-Bromo-4,5-difluoro-1- (methoxymethoxymethyl) benzene XH-NMR (300.058 MHz, CDC13) 6 ppm 3.42 (s, 3H), 4.57 (d, J = 1.2 Hz, 2H), 4.76 (s, 2H), 7.3-7.5 (m, 2H). 3.2. e 2-Bromo-5-cyano-l- (methoxymethoxymethyl) benzene XH-NMR (300.058 MHz, CDC13) d ppm 3.43 (s, 3H), 4.65 (s, 2H), 4.80 (s, 2H), 7.43 (dd) , J = 8.2, 4.1 Hz, 1H), 7.66 (d, J "= 8.2 Hz, 1H), 7.82 (d, J = 4.1 Hz, 1H) 3.2.f 2-Bromo-5-methoxy-l- ( methoxymethoxymethyl) benzene XH NMR (300 MHz, DMSO-d6): d 7.48 (dd, Ji = 1.2 Hz, J2 = 1.2 Hz, 1H), 7.05 (d, J = 2.7 Hz, 1H), 6.83 (dd, J1 = 3 Hz, J2 = 3 Hz, 1H), 4.69 (d, J = 1.2 Hz, 2H), 4.5 (s, 2H), 3.74 (d, J = 1.5 Hz, 3H), 3.32 (d, J = 2.1 Hz, 3H) ppm. 3.2.g 1-Benzyl-1- (2-bromo phenyl) -1- (methoxymethoxy) ethane XH NMR (300 MHz, DMSO-d6): d 1.10-1.67 (m, 1H), 7.25-7.09 (m, 6H ), 6.96-6.93 (m, 2H), 4.61 (d, 1H), 4.48 (d, 1H), 3.36-3.26 (m, 2H), 3.22 (s, 3H) and 1.63 (s, 3H) ppm. 3.2.h 2-Bromo-β-fluoro-1- (methoxymethoxymethyl) benzene XH-NMR (300 MHz, CDC13) d (ppm) 3.43 (S, 3H), 4.74 (s, 2H), 4.76 (d, J = 2.1 Hz, 2H), 7.05 (t, J = 9.1 Hz, 1H), 7.18 (td, J = 8.2, 5.9 Hz, 1H), 7.40 (d, J = 8.2 Hz, 1H). 3. 2.i 2-Bromo-4- (4-cyano phenoxy) -1- (methoxymethoxymethyl) benzene XH NMR (300 MHz, DMSO-d6): d 7.84 (d, 2H), 7.56 (d, 1H), 7.44 ( d, 1H), 7.19-7.12 (m, 3H), 4.69 (e, 2H), 4.56 (s, 2H) and 3.31 (s, 3H) ppm. 3.2.j 2-Bromo-S- (tert-butyldimethylsiloxy) -1- (methoxymethoxymethyl) benzene XH-NMR (300 MHz, CDCl3) d (ppm) 0.19 (s, 6H), 0.98 (s, 9H), 3.43 (s, 3H), 4.59 (s, 2H), 4.75 (s, 2H), 6.64 (dd, J = 8.5, 2.9 Hz, 1H), 6.98 (d, J = 2.9 Hz, 1H), 7.36 (d, J = 8.5 Hz, 1H). 3.2.k 2-Bromo-5- (2-cyano phenoxy) -1- (methoxymethoxymethyl) benzene-RMN (300 MHz, CDC13) d (ppm) 3.41 (s, 3H), 4.64 (s, 2H), 4.76 (s, 2H), 6.8-6.9 (m, 2H), 7.16 (td,, 7 = 7.6, 0.9 Hz, 1H), 7.28 (d, J = 2.9 Hz, 1H), 7.49 (ddd, J = 8.8, 7.6, 1.8 Hz, 1H), 7.56 (d, J = 8.5 Hz, 1H), 7.67 (dd, J = 7.9, 1.8 Hz, 1H). 3.2.1 2-Bromo-5 phenoxy-1 - (methoxymethoxymethyl) benzene ^ -NMR (300 MHz, CDCl 3) d (ppm) 3.40 (s, 3H), 4.62 (s, 2H), 4.74 (s, 2H), 6.80 (dd, J = 8.8, 2.9 hz, 1H), 7.01 ( d, J = 8.5 Hz, 2H), 7.12 (t, J = 7.9 Hz, 1H), 7.19 (d, J = 2.9 hz, 1H), 7.35 (1, J = 7.6 Hz, 2H), 7.48 (d, J = 8.5 Hz, 1H). Additional examples of compounds that can be produced by means of this method include 2-bromo-l- (methoxymethoxymethyl) benzene; 2-bromo-5-methyl-l- (methoxymethoxymethyl) benzene; 2-bromo-5- (methoxymethoxymethyl) -1- (methoxymethoxymethyl) benzene; 2-bromo-5-fluoro-l- (methoxymethoxymethyl) benzene; l-bromo-2- (methoxymethoxymethyl) naphthalene; 2-bromo-4-fluoro-1- (methoxymethoxymethyl) benzene; 2-phenyl-1- (2-bromophenyl) -1- (methoxymethoxy) ethane; 2-bromo-5- (4-cyanophenoxy) -1- (methoxymethoxy) methylbenzene; 2-bromo-4- (3-cyanophenoxy) -1- (methoxymethoxymethyl) benzene; 2-bromo-4- (4-chlorophenoxy) -1- (methoxymethoxymethyl) benzene; 2-bromo-4-phenoxy-1- (ethoxymethoxymethyl) benzene; 2-bromo-5- (3,4-dicyanophenoxy) -1- (methoxymethoxymethyl) benzene. Example 4 Preparation of I from 4 by 5 4. 1 Metalation and boronylation To a solution of 4 (17.3 mmol) in anhydrous THF (80 mL) at -78 ° C under nitrogen was added dropwise ter-BuLi or n-BuLi (11.7 mL) and the solution turned brown. . Then, B (OMe) 3 (1.93 mL, 17.3 mmol) was injected in one portion and the cooling bath was removed. The mixture was gradually heated with stirring for 30 min and then stirred with a water bath for 2 h. After adding 6N HCl (6 mL), the mixture was stirred overnight at room temperature and about 50% hydrolysis occurred as shown by TLC analysis. The solution was rotary evaporated and the residue was dissolved in MeOH (50 mL) and 6N HCl (4 mL). The solution was refluxed for 1 h and the hydrolysis was completed as indicated by TLC analysis. Rotary evaporation gave a residue which was dissolved in EtOAc, washed with water, dried and then evaporated. The crude product was purified by flash column chromatography on silica gel to provide a solid with 80% purity. The solid was further purified by washing with hexane to provide 7.2 mmole of I. 4.2 Reagent Analysis data are provided below for exemplary compounds of structure I. 4.2. to 5-Chloro-l, 3-dihydro-l-hydroxy-2, 1-benzoxazole 5-chlorobenzo [c] [1, 2] oxaborol-1 (3H) -ol (Cl) P.F .. 142-150 ° C. MS (ESI): m / z = 169 (M + l, positive) and 167 (M-l, negative). HPLC (220 nm): 99% purity. 1H NMR (300 MHz, DMSO-de): d 9.30 (s, 1H), 7.71 (d, J = 7.8 Hz, 1H), 7. 49 (s, 1H), 7.38 (d, J = 7.8 Hz, 1H) and 4.96 (s, 2H) ppm. 4.2.b 1, 3 -D? H? Dro-1-hydroxy-2, 1-benzoxazole benzofc] [1, 2] oxaborol-l (3H) -ol (C2) P.F .. 83-86 ° C. MS (ESI): m / z = 135 (M + l, positive) and 133 (M-l, negative). HPLC (220 nm): 95.4% purity. H NMR (300 MHz, DMSO-de): d 9.14 (s, 1H), 7.71 (d, J = 7.2 Hz, 1H), 7.45 (t, J = 7.5 Hz, 1H), 7.38 (d, J = 7.5 Hz, 1H), 7.32 (t, J = 7.1 Hz, 1H) and 4.97 (s, 2H) ppm. 4.2.c 5-chloro-3-methylbenzo [c] [1, 21-oxabole-l (3H) -01 (C3) XH-NMR (300 MHz, DMSO-d6) d ppm 1.37 (d, J = 6.4 Hz, 3H), 5.17 (q, J = 6.4 Hz, 1 H), 7.14 (m, 1H), 7.25 (dd, J = 9.7, 2.3 Hz, 1H), 7.70 (dd, J = 8.2, 5.9 Hz, 1H) , 9.14 (s, 1H). 4.2.d 6-Fluoro-l-hydroxy-l, 2, 3, 4-tetrahydro-2, 1-benzoxaborine 6-fluoro-3,4-dihydrobenzoic] [1,2] oxaborinin-l-ol (C4) XH -NRM (300 MHz, DMSO-d6) d ppm 2.86 (t, J = 5.9 Hz, 2H), 4.04 (t, J = 5.9 Hz, 2H), 7.0-7.1 (m, 2H), 7.69 (dd, J = 8.2, 7.2 Hz, 1H), 8.47 (s, 1H). 4.2.e 5,6-Difluoro-1,3-dihydro-l-hydroxy-2, 1-benzoxazole 5,6-difluorobenzo [c] [1, 2] oxaborol-1 (3H) -ol (C5) ^ - NMR (300 MHz, DMSO-d6) d ppm 4.94 (s, 2H), 7.50 (dd, J = 10.7, 6.8 Hz, 1H), 7.62 (dd, J = 9.7, 8.2 Hz, 1H), 9.34 (S, 1 HOUR) . 4. 2. f 5-cyano-l, 3-dihydro-l-hydroxy-2, 1-benzoxazole 1-hydroxy-l, 3-dihydrobenzo [c] [1, 2] oxaborol-5-carbonitrile (C6) XH-NMR (300 MHz, DMSO-d6) d ppm 5.03 (s, 2H), 7.76 (d, J = 8.2 Hz, 1H), 7.89 (d, J = 8.2 Hz, 1H), 7.90 (s, 1H), 9.53 ( s, 1H). 4.2.gl, 3-Dihydro-l-hydroxy-5-methoxy-2, 1-benzoxazole 5-methoxybenzo [c] [1,2] oxaborol-l (3H) -ol (C7) PF 102-104 ° C . MS ESI: m / z = 165.3 (M + 1) and 162.9 (M-1). XH NMR (300 MHz, EMSO-de): d 8.95 (s, 1H), 7.60. { d, J = 8.1 Hz, 1H), 6.94 (s, 1H), 6.88 (d, J = 8.1 Hz, 1H), 4.91 (s, 2H), 3.77 (s, 3 H) ppm. 4.2.h l, 3-Dihydro-l-hydroxy-5-methyl-2, 1-benzoxazole 5-methylbenzotc] [1,2] oxaborol-l (3H) -ol (C8) P.F .. 124-128 ° C. ESI MS: m / z = 148.9 (M + l) and 146.9 (M-l). XH NMR (300 MHz, EMSO-de): d 9.05 (s, 1H), 7.58 (d, J = 7.2 Hz, 1H), 7.18 (s, 1H), 7.13 (d, J = 7.2 Hz, 2H), 4.91 (s, 2H), 2.33 (s, 3H) p? . 4.2. i 1, 3-Dihydro-1-hydroxy-5-hydroxymethyl-2-, 1-benzoxazole 5- (hydroxymethyl) benzo.c] [1,2] oxaborol-l (3H) -ol (C9) MS: m / z = 163 (Ml, ESI-). 1 H NMR (300 MHz, DMSO-d 6): d 9.08 (s, 1H), 7.64 (d, 1H), 7.33 (s, 1H), 7.27 (d, 1H), 5.23 (t, 1H), 4.96 (s) , 2H), 4.53 (d, 2H) ppm. 4.2. j l, 3-Dihydro-5-fluoro-l-hydroxy-2, l-benzoxazole 5-fluorobenzo [c] [1, 2] oxaborol-l (3H) -ol (CIO) P.F .. 110-114 ° C. ESI MS: m / z = 150.9 (M-l). X H NMR (300 MHz, DMSO-de): d 9.20 (s, 1 H), 7.73 (dd, J x = 6 Hz, J 2 = 6 Hz, 1 H), 7.21 (m, 1 H), 7.14 (m, 1 H), 4.95 (s, 2H) ppm. 4.2.k 1, 3-Dihydro-2-oxa-l-cyclopenta [a] naphthalene naphtho [l, 2-c] [1, 2] oxaborol-1, (3H) -ol (Cll) P.F. 139-143 ° C. ESI MS: m / z = 184.9 (M + l). XH NMR (300 MHz, DMSO-d6): d 9.21 (s, 1H), 8.28 (dd, J? = 6.9 Hz, J2 = 0. 6 Hz, 1H), 7.99 (d, J = 8.1 Hz, 1H), 7.95 (d, J = 7.5 Hz, 1H), 7.59-7.47 (m, 3H), 5.09 (s, 2H) ppm. 4.2.m 1, 3-Dihydro-6-fluoro-l-hydroxy-2, 1-benzoxazole 6 f luorobenzo [c] [1,2] oxaborol-1 (3H) -ol (C13) PF.110-117.5 ° C. MS (ESI): m / z = 151 (M-1, negative). HPLC (220 nm): 100% purity. XH NMR (300 MHz, DMSO-de): d 9.29 (s, 1H), 7.46-7.41 (m, 2H), 7.29 (td, 1H) and 4. 95 (s, 2H) ppm. 4.2.n 3-Benzyl-l, 3-dihydro-1-hydroxy-3-methyl-2, 1-benzoxazole 3-benzyl-3-methylbenzo [c] [1, 21 -oxaborol-l (3H) -ol (C14) MS (ESI): m / z = 239 (M + 1, positive). HPLC: 99.5% purity at 220 nm and 95.9% at 254 nm. X H NMR (300 MHz, DMSO-d 6): d 8.89 (s, 1 H), 7.49-7.40 (m, 3 H), 7.25-7.19 (m, 1 H), 7.09-7.05 (m, 3 H), 6.96-6.94 ( m, 2H), 3.10 (d, 1H), 3.00 (d, 1H) and 1.44 (s, 3H) ppm. 4. 2. or 3-Benzyl-l, 3-dihydro-1-hydroxy -2, 1-benz oxaborol 3-benzylbenzo [c] [1, 2] oxaborol -1 (3H) -ol (C15) MS (ESI +): m / z = 225 (M + l). HPLC: 93.4% purity at 220 nm. X H NMR (300 MHz, DMSO-de): d 9.08 (s, 1 H), 7.63 (dd, 1 H), 7.43 (t, 1 H), 7.35-7.14 (m, 7 H), 5.38 (dd, 1 H), 3.21 (dd, 1H) and 2.77 (dd, 1H) ppm. 4.2.p 1, 3-Dihydro-4-fluoro-l-hydroxy-2, l-benzoxazole 4-f luorobenzo [c] [1,2] oxaborol-l (3H) -ol (C16) ^ -RMN (300 MHz, DMSO-de) d (ppm) 5.06 (s, 2H), 7.26 (ddd, J = 9. 7, 7.9, 0.6 Hz, 1H), 7.40 (td, J = 8.2, 4.7 Hz, 1H), 7.55 (d, J = 7.0 Hz, 1H), 9.41 (s, 1H). 4.2.q 5- (4-cyano phenoxy) -1,3-dihydro-1-hydroxy-2, 1-benzoxazole 4- (1-hydroxy-], 3-dihydrobenzo [c] [1,2] oxaborol-5 -ylaxy) benzonitrile (C17) XH-NMR (300 MHz, EMSO-de) d ppm 4.95 (S, 2H), 7.08. { dd, J = 7.9, 2.1 Hz, 1H), 7.14 (d, J = 8.8 Hz, 1H), 7.15 (d, J = 2.1 Hz, IH), 7.78 (d, J = 7.9 Hz, 1H), 7.85 ( d, J = 9.1 Hz, 2H), 9.22 (s, 1H). 4.2.r 6- (4-cyano phenoxy) -1,3-dihydro-l-hydroxy-2, 1-benzoxazole 4- (1-hydroxy-1,3-dihydrobenzo [c] [1,2] oxaborol-6 iloxy) benzonitrile (C18) PF.148-151 ° C. MS: m / z = 252 (M + 1) (ESI +) and m / z = 250 (M-1) (ESI-). CLAR: 100% purity at 254 nm and 9 € .7% at 220 nm. X H NMR (300 MHz, DMSO-d 6): d 9.26 (s, 1 H), 7.82 (d, 2 H), 7. 50 (d, 1H), 7.39 (d, 1H), 7.26 (dd, 1H), 7.08 (d, 2H) and 4.99 (s, 2H) ppm 4.2.e 6- (3-cyano phenoxy) -1, 3 -dihydro-l-hydroxy-2, 1-benzoxazole 3- (1-hydroxy-l, 3-dihydrobenzo [c] [1, 2] oxaborol-6-yloxy) benzonitrile (C19) PF.146-149 ° C. MS: m / z = 252 (M + 1) (ESI +) and m / z = 250 (M-1) (ESI-). HPLC: 100% purity at 254 nm and 97.9% at 220 nm. X H NMR (300 MHz, DMSO-d 6): d 9.21 (s, 1H), 7.60-7.54 (, 2H), 7.50-7.45 (m, 2H), 7.34-7.30 (m, 2H), 7.23 (dd, 1H ) and 4.98 (s, 2H) ppm. 4.2. t 6- (4-Chloro phenoxy) -1,3-dihydro-l-hydroxy-2, 1-benzoxazole 6- (4-chloroenoxi) benzo [c] [1,2] oxaborol -1 (3H) -ol (C20) PF.119-130 ° C. MS: m / z = 261 (M + 1) (ESI +) and m / z = 259 (M-1) (ESI-). HPLC: 100% purity at 254 nm and 98.9% a 220 nm. X H NMR (300 MHz, DMSO-d 6): d 9.18 (s, 1H), 7.45-7.41 (m, 3H), 7.29 (d, 1H), 7.19 (dd, 1H), 7.01 (d, 2H) and 4.96 (s, 2H) ppm. 4.2. u 6-Phenoxy-1, 3-dihydro-1-hydroxy-2, 1-benzoxazole 6-phenoxybenzo [e] [1, 2] oxaborol-1 (3H) -ol (C21) PF.95-99 C. MS : m / z = 227 (M + l) (ESI +) and m / z = 225 (Ml) (ESI-). HPLC: 100% purity at 254 nm and 98.4% at 220 nm. X H NMR (300 MHz, DMSO-d 6): d 9.17 (s, 1 H), 7.43-7.35 (m, 31-1), 7.28 (s, 1H), 7.19-7.09 (m, 2H), 6.99 (d, 2H) and 4.96 (s, 2H) ppm. 4.2. v 5- (4-Cyanobenzyloxy) -1,3-dihydro-l-hydroxy-2-, 1-benzoxazole 4- ((1-hydroxy-1,3-dihydrobenzo [c] [1,2] oxaborol-5-yloxy) ) methyl) benzonitrile (C22) ^ -RMN (300 MHz, DMSO-d6) d (ppm) 4.90 (s, 2H), 5.25 (s, 2H), 6.98 (dd, J = 7.9, 2.1 Hz, 1H), 7.03 (d, J = 1.8 Hz, 1H), 7.62 (d, J = 7.9 Hz, 1H), 7.64 (d, J = 8.5 Hz, 2H), 7.86 (d, J = 8.5 Hz, 1H), 9.01 ( s, 1H). 4.2. w 5- (2-cyano phenoxy) -1,3-dihydro-1-hydroxy-2-, 1-benzoxazole 2- (1-hydroxy-1,3-dihydrobenzo [c] [1,2] oxaborol-5-yloxy ) benzonitrile (C23) ^ -RMN (300 MHz, DMSO-d6) d (ppm) 4.95 (S, 2H), 7.0-7.2 (m, 3H), 7.32 (td, J = 7.6, 1.2 Hz, 1H), 7.68 (ddd, J = 9.1, 7.6, 1.8 Hz, 1H), 7.77 (d, J = 7.9 Hz, 1H), 7.91 (dd, J = 7.9, 1.8 Hz, 1H). 4.2.x 5-Phenoxy-l, 3-dihydro-l-hydroxy-2, 1-benzoxazole 5-phenoxybenzo [c]. { 1, 2] oxaborol-l (3H) -ol (C24) ^ -RM (300 MHz, DMSO-d6) d (ppm) 4.91 (s, 2H), 6.94 (s, 1H), 6.96 (d, J = 8.8 Hz, 1H), 7.05 (d, J = 7.6 Hz, 2H), 7.17 (t, J = 7.3 Hz, 1H), 7.41 (t, J = 7.3 Hz , 2H), 7.70 (d, J = 8.5 Hz, 1H), 9.11 (s, 1H). 4.2. and 5- [4- (N, N-Diethylcarbamoyl) phenoxy] -1,3-dihydro-1-hydroxy-2, 1-benzoxazole N, N-diethyl-4- (l-hydroxy-l, 3-dihydrobenzo [ c] [1,2] oxaborol-5-yloxy) benzamide (C25) ^ -RMN (300 MHz, DMSO-d6) d (ppm) 1.08 (br s, 611), 3. 1-3.5 (m, 4H), 4.93 (s, 2H), 7.0-7.1 (m, 4H), 7.37 (d, J = 8.5 Hz, 2H), 7.73 (d, J = 7.9 Hz, 1H), 9.15 (s, 1H). 4.2. z 1, 3-Dihydro-l-hydroxy-5- [4- (morpholinocarbonyl) phenoxy] -2, 1-benzoxazole (4- (1-hydroxy-l, 3-dihydrobenzo [c] [1,2] oxaborol- 5-yloxy) phenyl) (morpholino) methanone (C26) ^ -RMN (300 MHz, DMSO-d6) d (ppm) 3.3-3.7 (m, 8H), 4. 93 (s, 2H), 7: 0-7.1 (m, 4H), 7.44 (d, J = 8.8 Hz, 2H), 7.73 (d, J = 7.9 Hz, 1H), 9.16 (s, 1H). 4.2. aa 5- (3,4-Di-cyano phenoxy) -1,3-dihydro-l-hydroxy-2, 1-benzoxazole 4- (1-hydroxy-l, 3-dihydrobenzo [c] [1,2] oxaborol- 5-yloxy) phthalonitrile (C27) ^ -NRM (300 MHz, DMSO-de) d (ppm) 4.97 (s, 2H), 7.13 (dd, J = 7.9, 2.1 Hz, 1H), 7.21 (d, J = 1.5 Hz, 1H), 7.43 (dd, J = 8.8, 2.6 Hz, 1H), 7.81 (d, J = 7.9 Hz, 1H), 7.82 (d, J = 2.6 Hz, 1H), 8.11 (d, J = 8.5 Hz, 1H), 9.26 (s, 1H). 4.2. ab 6-Phenylthio-l, 3-dihydro-l-hydroxy-2, 1-benzoxazole 6- (phenylthio) benzo [c] [1,2] oxaborol-l (3H) -ol (C28) PF.121- 124 ° C. MS: m / z = 243 (M + 1) (ESI +) and m / z = 241 (M-1) (ESI-). HPLC: 99.6% purity at 254 nm and 99.6% at 220 nm. X H NMR (300 MHz, DMSO-de): d 9.25 (s, 1H), 7.72 (dd, 1H), 7.48 (dd, 1H), 7.43 (dd, 1H), 7.37-7.31 (m, 2H), 7.29 -7.23 (m, 3H), and 4.98 (s, 2H) ppm. 4.2. ac 6- (4-trif luoromethoxy-enoxy) -1,3-dihydro-l-hydroxy-2, 1-benzoxazole 6- (4- (trifluoromethoxy) phenoxy) benzo [c] [1,2] oxaborol-1 (3H ) -ol (C29) PF.97-101 ° C. MS: m / z = 311 (M + 1) (ESI +) and m / z = 309 (M-1) (ESI-). HPLC: 100% purity at 254 nm and 100% at 220 nm. XH (300 MHz, DMSO-d6): d 9.20 (s, 1H), 7.45 (d, 1H), 7.37 (d, 2H), 7.33 (d, 11-1), 7.21 (dd, 1H), 7.08 ( d, 211), and 4.97 (s, 2H) ppm. 4.2. ad 5- (N-Methyl-N-phenylene-sulfonylamino) -1,3-dihydro-1-hydroxy-2, 1-benzoxazole N- (1-hydroxy-l, 3-dihydrobenzo { c] [1, 2] oxaborol-5-yl) -N-met i lbencensulfonamide (C30) P. F. .85-95 ° C. MS: m / z = 304 (M + 1) (ESI +) and m / z = 302 (M-1) (ESI-). HPLC: 96.6% purity at 254 nm and 89.8% at 220 nm. X H NMR (300 MHz, DMSO-d 6): d 9.23 (s, 1 H), 7.72-7.63 (m, 2H), 7.56 (t, 2H), 7.50 (d, 2H), 7.16 (s, 1H), 7.03 (d, 1H), 4.91 (s, 2H) and 3.14 (s, 3H) ppm. 4.2.ae 6- (4-Methoxy phenoxy) -1,3-dihydro-l-hydroxy-2, 1-benzoxazole 6- (4-methoxyphenoxy) benzo [c] [1,2] oxaborol-l (3 H) -ol (C31) PF.126-129 ° C. MS: m / z = 257 (M + 1) (ESI +) and m / z = 255 (M-1) (ESI-). HPLC: 98.4% purity at 254 nm and 98.4% at 220 nm. hl NMR (300 MHz, EMSO-de): d? .14 (s, 1H), 7.36 (d, 1H), 7.19 (s, 1H), 7.12 (d, 1H), 6. 98 (d, 2H), 6.95 (d, 2H), 4.93 (s, 2H) and 3.73 (s, 3H) p n. 4.2. af 6- (4-Methoxy phenylthio) -l, 3-dihydro-l-hydroxy-2, 1-benzoxazole 6- (4-methoxy-enylthio) benzo [c] [1,2] oxaborol-l (3H) -ol (C32) PF.95-100 ° C. MS: m / z = 272 (M +), 273 (M + l) (ESI +) and m / z = 271 (M-l) (ESI-). HPLC: 100% purity at 254 nm and 99.2% at 220 nm. hl NMR (300 MHz, EMSO-de): d 9.20 (s, 1H), 7.51 (d, 1H), 7.39-7.28 (m, 4H), 6.98 (d, 2H), 4.93 (s, 2H) and 3.76 (s, 3H) ppm. 4.2.ag 6- (4-Methoxy-phenyleulfonyl) -1,3-dihydro-l-hydroxy-2,1-benzoxazole 6- (4-methoxyphenylsulfonyl) benzo [c] [1,2] oxaborol-1 ( 3H) -ol (C33) PF.180-192 ° C. MS: m / z = 305 (M + 1) (ESI +) and m / z = 303 (M-1) (ESI-). HPLC: 96.8% purity at 254 nm and 95.5% at 220 nm. X H NMR (300 MHz, DMSO-d 6): d 9.46 (s, 1 H), 8.28 (s, 1H), 7.99 (d, 1H), 7.85 (d, 2H), 7.61 (d, 1H), 7.11 (d, 2H), 5.02 (s, 2H) and 3.80 (s, 3H) ppm. Four . 2. ah 6- (4-Methoxyphenylene-purinyl) -l, 3-dihydro-l-5-hydroxy-2-, 1-benzoxazole 6- (4-methoxyphenylsulfinyl) benzo [c] [1,2] oxaborol-1 (3 H ) -ol (C34) l? ñ NMR (300 MHz, DMSO-d6): d 9.37 (s, 1H), 8.02 (d, 1H), 7.71 (dd, 1H), 7.59 (d, 2H), 7.53 (d, 1H), 7.07 (d, 2H), 0 5.00 (s, 2H) and 3.76 (s, 3H) ppm. Four . 2. ai 5-Trifluoromethyl-1, 3-dihydro-l-hydroxy -2, 1-benzoxazole 5- (trifluoromethyl) benzo [c] [1,2] oxaborol-1 (3H) -ol (C35) 5 PF. 113-118 ° C. MS: m / z = 203 (M + l) (ESI +) and m / z = 201 (M-l) (ESI-). HPLC: 100% purity at 254 nm and 100% at 220 nm. K NMR (300 MHz, DMSO-de): d 9.48 (s, 1H), 7.92 (d, 1H), 7.78 (s, 1H), 7.67 (d, 1H) and 5.06 (s, 2H) ppm. «4.2. aj 4- (4-Cyano phenoxy) -1,3-dihydro-l-hydroxy-21-benz oxaborol 4- (1-hydroxy-l, 3-dihydrobenzo [c] [1,2] oxaborol-4-yloxy) benzonitrile For coupling reaction between 4-c fluorobenzonitrile and substituted phenol to give starting material 2, see Igarashi, S .; et al. Chemical & Pharmaceutical Bulletin (2000), 48 (11), 1689-1697. XH-NMR (300 MHz, DMSO-d6) (ppm) 4.84 (s, 2H), 7.08 (d, J = 8.2 Hz, 2H), 7.18 (d, J = 7.9 Hz, 1H), 7.45 (t, J) = 7.3 Hz, 1H), 7.63 (d, J = 7.3 Hz, 1H), 7.82 (d, J = 8.5 Hz, 2H). 4.2. ak 5- (3-cyano phenoxy) -1,3-dihydro-1-hydroxy-2, 1-benzoxazole 3- (1-hydroxy-1,3-dihydrobenzo [c] [1,2] oxaborol-5-yloxy ) benzonitrile (C36) For coupling between 3-fluorobenzonitrile and substituted phenol to give starting material 2: Li, F. et al. , Organic Lettere (2003), 5 (12), 2169-2171. X H-NMR (300 MHz, DMSO-d 6) (ppm) 4.93 (s, 2 H), 7.0-7.1 (m, 2 H), 7.3 7.4 (m, 1 H), 7.5-7.7 (m, 3 H), 7.75 ( d, J = 8.2 Hz, 1H). 4. 2. to 5- (4- Carboxy phenoxy) -1, 3-dihydro-1-hydroxy-2, 1-benzoxazole 4- (1-hydroxy-1,3-dihydrobenzo [c] [1, 2] oxaborol-5-yloxy) benzoic acid (C38) To a solution of 5- (4-cyanophenoxy) -l-hydroxy-2, 1-benzoxazole obtained in C17 (430 mg, 1.71 mmol) in ethanol (10 mL) was added 6 moles / L sodium hydroxide (2 mL), and the mixture was refluxed for 3 hours. Hydrochloric acid (6 mol / L, 3 mL) was added and the mixture was extracted with ethyl acetate. The organic layer was washed with brine and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure, and the residue was purified by column chromatography on silica gel (ethyl acetate) followed by trituration with disopropyl ether to give the objective compound (37 mg, 8%). ^ -RMN (300 MHz, DMSO-de) d (ppm) 4.94 (s, 2H), 7.0-7.1 (m, 4H), 7.76 (d, J = 7.9 Hz, 1H), 7.94 (d, J = 8.8 Hz, 2H), 9.19 (s, 11-1), 12.8 (br s, 1H). 4.2. am 1-Hydroxy-1, 3-dihydro-5-f4- (tetrazol-1-yl) phenoxy] -2, 1-benzoxazole 5- (4- (lH-tetrazol-5-yl) phenoxy) benzo [c] [ 1,2] oxaborol-l (3H) -ol (C39) A mixture of 5- (4-cyanophenoxy) -l-hydroxy-2, 1-benzoxazole (200 mg, 0.797 mmol), sodium azide (103 mg, 1.59 mmole) and ammonium chloride (85 mg, 1.6 mmole) in N, N-dimethylformamide (5 mL) was stirred at 80 ° C for 2 days. Water was added thereto, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and brine, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure, and the residue was purified by column chromatography on silica gel (ethyl acetate) followed by trituration with ethyl acetate to give the objective compound (55 mg, 23%). ^ -RMN (300 MHz, DMSO-d6) d (ppm) 4.95 (s, 2H), 7.0-7.1 (m, 2H), 7.23 (d, J = 8.8 Hz, 2H), 7.76 (d, J = 7.9 Hz, 1H), 8.05 (d, J = 8.5 Hz, 2H), 9.18 (br s, 1H). Example 5 Preparation of I from 2 by 6 5. 1 Boronylation, Reduction and Catalytic Cyclization A mixture of 2 (10.0 mmol), bis (pinacolato) diboro (2.79 g, 11.0 mmol), PdCl2 (dppf) (250 mg, 3 mol%), and potassium acetate (2.94 g, 30.0 mmol) in 1,4-dioxane (40 mL) was stirred at 80 ° C during the night. Water was added thereto, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure. The crude product was dissolved in tetrahydrofuran (80 mL), then sodium periodate (5.56 g, 26.0 mmol) was added. After stirring at room temperature for 30 min, 2N HCl (10 mL) was added, and the mixture was stirred at room temperature overnight. Water was added thereto, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure, and the residue was treated with ether to provide 6.3 mmoles of the corresponding boronic acid. To the boronic acid solution obtained (0.595 mmoles) in methanol (5 mL) was added sodium borohydride (11 mg, 0.30 mmol), and the mixture was stirred at room temperature for 1 h. Water was added thereto, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure, and the residue was purified by column chromatography on silica gel to give 0.217 mmole of I. 5. Reagent Analysis data for exemplary compounds of structure I are given below. 5. 2. to 1, 3-Dihydro-5-fluoro-l-hydroxy-2, 1-benzoxazole (CIO) The analysis data for this compound are listed in 4.2. j. Example 6 Preparation of I from 3 6. 1 Boronium and cyclization of a vessel To a solution of 3 (4.88 mmole) and triisopropyl borate (1.35 mL, 5.86 mmole) in tetrahydrofuran (10 mL) was added n- butyllithium (1.6 mol / L in hexanes, 6.7 mL, 10.7 mmol) was dripped for 15 min at -78 ° C under nitrogen atmosphere and the mixture was stirred for 2 h while it was allowed to warm to room temperature. The reaction was quenched with 2N HCl and extracted with ethyl acetate. The organic layer was washed with brine and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure, and the residue was purified by column chromatography on silica gel and treated with pentane to give 0.41 mmole of I. 6.2 Re-examined Analysis data for exemplary compounds of structure I are given below. 6.2. a 1, 3-Dihydro-5-fluoro-1-hydroxy-2, 1-benzoxazole (CIO) The analysis data for this compound are listed in 4.2. j. Example 7 Preparation of I from 3 7.1 Boronylation and cyclization of a vessel with deethylation To a solution of 3 (4.88 mmoles) in toluene (20 mL) was added triisopropyl borate (2.2 mL, 9.8 mmol), and the mixture it was heated to reflux for 1 h. The solvent, isopropyl alcohol generated and excess triisopropyl borate were removed under reduced pressure. The residue was dissolved in tetrahydrofuran (10 mL) and cooled to -78 ° C. N-Butyllithium (3.2 mL, 5.1 mmol) was added by dripping for 10 min and the mixture was stirred for 1 h while it was allowed to warm to room temperature. The reaction was quenched with 2N HCl, and extracted with ethyl acetate. The organic layer was washed with brine and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure, and the residue was purified by column chromatography on silica gel to give 1.54 mmole of I. 1.2 Resulted Analytical data for exemplary compounds of structure I are given below. 7.2. a l, 3-Dihydro-5-fluoro-l-hydroxy-2, l-benzoxazole (CIO) The analysis data for this compound are listed in 4.2. j. Example 8 Preparation of 8 from 7 8.1 Bromination A solution of 7 (49.5 mmol) in carbon tetrachloride (200 mL) N-bromosuccinimide (8.81 g, 49.5 mmol) and N, N-azoisobutylnitrile (414 mg) was added. , 5% moles), and the mixture was heated to reflux for 3 h. Water was added thereto, and the mixture was extracted with chloroform. The organic layer was washed with brine and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure to give the intermediate brominated with crude methyl 8. Example 9 Preparation of 3 from 8 9.1 Hi droxi lation 8 crude (49.5 mmoles) dimethylformamide (150 mL) and sodium acetate ( 20.5 g, 250 mmol), and the mixture was stirred at 80 ° C overnight. Water was added thereto, and the mixture was extracted with ether. The organic layer was washed with water and brine, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure. To the residue was added methanol (150 mL) and IN sodium hydroxide (50 mL), and the mixture was stirred at room temperature for 1 h. The reaction mixture was concentrated to approximately one third volume under reduced pressure. Water and hydrochloric acid were added thereto, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and brine, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure, and the residue was purified by column chromatography on silica gel followed by trituration with dichloromethane to give 21.8 mmoles of 3. 9.2 Resolutions Exemplary compounds of structure 3 prepared by the above method are given below. . 9.2. a 2-Bromo-5-cyanobenzyl alcohol-RMN (300 MHz, DMSO-d6) d ppm 4.51 (d, J = 5.9 Hz, 2H), 5.67 (t, J = 5.6 Hz, 1H), 7.67 (dd, J = 8.2, 2.0 Hz, 1H), 7. 80 (s, J = 8.2 Hz, 1H), 7.83 (d, J = 2.0 Hz, 1H). Additional examples of compounds that can be produced by this method include 2-bromo-5- (4-cyanophenoxy) benzyl alcohol. Example 10 Preparation of 9 from 2 10. 1 Reaction A mixture of 2 (20.0 mmoles), chloride (methoxymethyl) triphenylphosphonium (8.49 g, 24.0 mmol), and potassium tert-butoxide (2.83 g, 24.0 mol) in N, N-dimethylformamide (50 mL) was stirred at room temperature overnight. The reaction was quenched with 6Cl HCl, and the mixture was extracted with ethyl acetate. The organic layer was washed with water (x2) and brine, and dried over anhydrous sodium sulfate. The solvent was removed under reduction. To the residue were added tetrahydrofuran (60 mL) and HCl 6 ?, and the mixture was heated to reflux for 8 h. Water was added thereto, and the mixture was extracted with ether. The organic layer was washed with brine and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure to provide 16.6 mmol of 9. EXAMPLE 11 Step 13 Preparation Method 11. 1 Reaction A solution of I in a suitable alcohol solvent (RI-OH) was refluxed under a nitrogen atmosphere and then distilled to remove the alcohol to give the corresponding ester.

Example 12 Preparation of Ib from 12.1 Reaction To a solution of the in toluene was added amino alcohol and the participated solid was collected to give Ib. 12.2 Reected It was dissolved (500 mg, 3.3 mmol) in toluene (37 mL) at 80 ° C and ethanolamine (0.20 mL, 3.3 mmol) was added. The mixture was cooled to room temperature, then ice-bath, and filtered to give C40 as a white powder (600.5 mg, 94%). 12.2a Ethanolamine adduct of 1,3-dihydro-5-fluoro-1-hydroxy-2,1-benzoxazole (C40) XH-NMR (300 MHz, DMSO-d6) d (ppm) 2.88 (t, J = 6.2 Hz, 2H), 3.75 (t, J = 6.3 Hz, 2H), 4.66 (s, 2H), 5.77 (br, 2H), 6. 85-6.91 (m, 2H), 7.31 (td, J-7.2, 1.2 Hz, 1H). Example 13 Formulations The compounds of the present invention can be administered to a patient using a therapeutically effective amount of a compound described herein in any one of the following three lacquer formulations and a solvent formulation. The varnish formulation provides good durability while the solvent formulation provides good ease of use. These compounds can also be applied using an aerosol formulation, paint varnish, drops or others. 1. 1: 4 propylene glycol: ethanol; 1:10 p / vol compound of the invention; 2. 1: 4 ether poly (vinylmethyl-alt-monobutyl ester of maleic acid: ethanol; 1:10 p / vol compound of the invention; 3. 56% ethanol; 14% water; 15% polymethyl methacrylate; 2-hydroxyethyl), 5% dibutyl sebacate, 10% compound of the invention, 4. 55% ethanol, 15% ethyl acetate, 15% poly (vinyl acetate), 5% dibutyl sebacate. 10% Composite of the Invention The preparation of these formulations is well known in the art and is found in references such as Remington: The Science and Pharmacy Practice, supra.Example 14 Antifungal MIC Evaluation All MIC evaluations followed the guidelines of the National Committee Standards for Clinical Laboratories (NCCLS) for antimicrobial evaluation of yeasts (M27-A2 NCCLS) and filamentous fungi (Pfaller et al., NCCLS publication M38-A - Reference Method during Broth Dilution Antifungal Susceptibility Testing of Filamentous Fungi; Approved Standard. Wayne, PA: NCCLS; 2002 (Vol. 22, No. 16) except for the Malaeeezia species that were incubated in a urea broth (Nakamura et al., Antimicrobial Agent And Chemother apy, 2000, 44 (8) pp. 2185-2186). The results of the MIC evaluation are given in FIGS.1A-1C. EXAMPLE 15 KERATIN ASSAY Many antifungal agents bind strongly to keratin which not only reduces its antifungal potency but may also restrict its penetration into the nail. The affinities of the compounds for keratin dusts was determined by a method described in Tatsumi, Antimicrobial Agent and Chemo therap i, 46 (12): 3797-3801 (2002). A comparison of MIC data for various compounds of the invention against T rubrum, with and without the presence of 5% keratin, is provided in FIGS. 1A-1C. Example 16 Antifungal spectra (CIO) of activity (CIO) is a new compound in development for use as a topical antifungal treatment. The purpose of this study was to determine the minimum inhibitory concentration (MIC) for (CÍO) against fungal evaluation strains 19 including: Aepergilue fumigatus (A. fumigatus), Candida Albicane (C. albicane, both strains sensitive to fluconazole and resistants), Candida glabrata (C. glabrata), Candida krueei (C. krueei), Cryptococcus neoformans (C. neoformane), Candida parapeiloeie (C. parapeilosie), Candida tropicalie (C. tropicalis), Epidermophi ton floccoeum (E. floccoeum), Fuearium eolani (F. solani), Malaesezia fúrfur (M fúrfur), Malaeeezia pachidermatie (M pachi derma tie ), Malayeezia eympodialie (M eympodialie), Microeporum audouinii (M. audouinii), Microeporum canie (M canis), Microsporum gypseum (M gypeeum), Trichophi ton ment agrophi te (T mentagrophi tee), Trichophi ton rubrum (T. rubrum) , Trichophi ton toneurane (T. toneurane). Fungal growth was evaluated after exposure to different concentrations of (CIO). In addition, the MIC for (CIO) against T rubrum was also determined in the presence of 5% keratin powder and the minimum fungicidal concentration (MFC) for (CIO) against T rubrum and T. mentagrophi tee. Cyclopirox and / or terbinafine and / or fluconazole and / or itraconazole were used as comparators and evaluated similarly. These studies were carried out at NAEJA Pharmaceutical, Inc. Materials and methods Obtained (CIO) from Anacor Pharmaceuticals, Inc. (Palo Alto, CA, E.U.A.). ATCC strains of ATCC (Manassas, VA, E.U.A.) were obtained. Cyclopirox-olamine was obtained from Sigma-Aldrich Co. (St. Louis, MO, E.U.A.). Terbinafine, fluconazole and itraconazole were synthesized in NAEJA Pharmaceutical Inc. (Edmonton, AB, Canada), experimental procedures and analysis data for these standards were stored in NAEJA files. All MIC evaluations followed the guidelines of the National Clinical Laboratory Laboratory Standards (NCCLS) for antimicrobial evaluation of yeast and filamentous fungi (Pfaller et al., 2002) except for the Malaeeezia species that was incubated in a urea broth (Nakamura et al. al., 2000). The microcalde dilution method was used to evaluate the in vi tro activity (CIO) against fungal test strains 19. Briefly, compounds were dissolved in DMSO and diluted in sterile water to give a raw material. Serial dilutions were prepared twice from the raw material in 96-well plates and medium was added. The medium was RPMI, RPMI + MOPS, modified RPMI or modified urea broth. Plates were inoculated with fungal suspensions to give a final inoculum size of 0.5-2.5 x 103 cells / mL for yeast or 0.4-5 x 104 CFU / mL for filamentous fungi and then incubated for 24-168 h at 35 ° C. . The final concentration of DMSO did not exceed 5%. MIC was defined as the lowest concentration that resulted in a 90% reduction in growth, as compared to a drug-free control. CFM was defined as the lowest concentration that eliminated over 90% of the fungus, as compared to a drug-free control. Results and Conclusions The results for the MIC of (CIO) and reference compounds against strains 19 are shown in FIGS. 2A-2B. The results for the MFC of CIO against 2 strains of fungi are shown in Table 2. (CIO) had values that vary from 0.25 - 2 μg / mL against all the fungi evaluated. The addition of 5% keratin powder to the medium did not carry out the MIC against T rubrum. (CIO) had fungicidal activity against T. rubrum and T. mentagrophi tes with MFC values of 8 and 16 μg / mL, respectively. The reference compounds had MIC values in the range defined by NCCLS. Example 17 Determination of solubility, stability and Log P of compounds of the present invention by LC / MS / MS The solubility, stability at room temperature and Log P of CIO were determined by the following methodology. Reagents and standards: Ethanol: Alcohol grade ACS grade 200 (EM Science, Gibbstown, NJ, E.U.A.); Octanol: octyl alcohol (EM Science, Gibbstown, NJ, E.U.A.); Acetonitrile: CLAR grade (Burdick &Jackson, Muskegon, MI, E.U.A.); Ammonium acetate: lot 3272X49621 (Mallinckrodt, Phillipsburg, NJ, E.U.A.); CÍO: lot A032-103 (Anacor Pharmaceuticals, Palo Alto, CA, E.U.A.); p-Nitrophenol (PNP): OGNOl batch (TCI America, Portland, OR, E.U.A.); water: deionized water (from Millipore systems, Billerica, MA, USA) Solubility N-octanol and water were pre-saturated reciprocally by vigorous stirring of a mixture of both solvents for up to 12 hours and the mixture was allowed to separate. The solubility in each solvent was determined by adding 10 μL of 20, 40, 200, 1000 and 5000 μg / mL of CIO in DMSO to the n-octanol or pre-saturated water. After the sample was vortexed for 10 seconds, the sample was centrifuged for 10 min at about 3000 rpm. A visual inspection was made to determine if the sample was crystalline or if an apella had formed on the bottom of the tube. Log P CIO (10 μL of 5000 μg / mL) at 2X the final concentration was added to 0.5 mL pre-saturated n-octanol and mixed. An equal volume (0.5 mL) of pre-saturated water was added, mixed by vortex and then mixed on a rotary shaker for one now and 24 per tripilicate at approximately 25 ° C. The organic and aqueous layers were separated by centrifugation for 5 min at approximately 2000 rpm. Twenty-five μL of the octanol layer (top) were removed and placed in a pre-labeled one. Twenty-five μL of the aqueous layer (lower) were removed, taking care to avoid contamination with octanol and placed in a pre-labeled tube.

Stability at room temperature CIO (10 μL of 5000 μg / mL) was added to both 0.5 mL of n-octanol and 0.5 mL of water in triplicate. The samples were mixed. At 0 h and 24 h the samples were stored at approximately -20 ° C. Twenty-five μL of sample was used during the analysis. CIO extraction procedure For the octanol sample, 25 μL of ethanol, 25 μL of water and 300 μL of acetonitrile containing the internal standard were added. For the water sample was added 25 μL of ethanol, 25 μL of octanol and 300 μL of acetonitrile containing the internal standard [60 mL of acetonitrile addition 6 μL of PNP (1000 μg / mL)]. For the calibrators, 25 μL of octanol, 25 μL of water and 3O0 μL of acetonitrile containing the internal standard were added. The mixture was vortexed for 10 seconds. Two hundred μL of the organic layer was transferred to a clean deactivated autosampler vessel. Calculations A weighted linear regression of concentration / 1 was used during the quantification of CÍO. All the integration was carried out with peak areas using Analyst version 1.3, Applied Biosystems. For CÍO, peak area ratio analytes were used for PNP internal standard throughout the quantification. The division coefficient (P) was calculated according to the equation detailed below. P = [sample concentration] ocanol / [sample concentration] aga Log P = logio (division coefficient) Results: As shown in Table 17A the solubility of CIO in both octanol and water is very good on the scale of evaluated concentration. Table 17A Solubility of CIO in water and octanol Concentration Final Octanol Water (μg / mL) Visual Visual 0.800 Transparent Transparent 4.00 Transparent Transparent 20.0 Transparent Transparent 100 Transparent Transparent Table 17B shows the results of the log P determination after 1 h and 24 h for CÍO. The mean P log after 1 h was 1.97 (n = 3). After 24 h the concentrations in both the octanol layer and the water layer remained the same. The mean P log after 24 h was 1.93 (n = 3).

Table 17B Log P of CIO Sample Conc. In water Conc. In Log P (μg / mL) Octanol (μg / mL) 1 h-1 1.26 108 1.93 lh-2 1.21 103 1.93 lh-3 1.05 115 2.04 24h-l 1.27 104 1.91 24h-2 1.17 109 1.97 24h-3 1.28 99.0 1.89 A stability study for CIO was conducted at room temperature for 24 hours without continuous mixing. Table 17C shows that CIO in pure water and octanol is stable for 24 hours. Table 17C. Stability of water and octanol for CIO at room temperature after 24 h.

Sample Medium SD Percentage (μg / mL) remaining 24 hours against og Water-Oh 82.5 3.72 115 Water-24h 95.0 21.4 Octanol-Oh 115 3.06 93 Octanol-24h 107 6.11 Example 18 Determination of CIO Penetration in the human nail Were taken performed two nail penetration studies based on the protocol in Hui et al. , Journal of Pharmaceutical Sciences, 91 (1): 189-195 (2002) ("Hui protocol"). The purpose of this study was to determine and compare the penetration and distribution of CÍO in carrier in the human nail plate in vi tro in relation to 8% of ciclopirox p / p in commercial varnish (Penlac®). MATERIALS AND METHODS Article evaluation and dose formulation 8% ciclopirox p / p in commercial varnish was manufactured by Dermick (Berwyn, PA). The radiochemical purity and specific activity of the chemical was determined as > 95% and 12.5 mCi / mmoles, respectively. The study was made up of two groups. The compositions (% by weight) of the dose formulations are as follows: Active radiolabeling compound in four groups. Groups * Chemical Dosage of radioactivity test (x 14 days) (%) (per 10 μL) A (C10) qd 10 0.19 μCi C (Cyclopirox) qd 8 0.22 μCi * A = Group CÍO, C = group Ciclopirox Human nails Plates were collected with healthy human fingernails from adult human cadavers and stored in a container closed at 0 - 4 ° C. Before the experiment, the plates were lightly washed with nails with normal saline to remove any contamination, then rehydrated by placing them for three hours on a cloth moistened with normal saline. The nail samples were randomly selected into four groups. 0 Surface dosing and washing procedures Preparation of doses: The radioactivity of each group is approximately 0.19 ± 0.01 and 0.22 ± 0.03 μCi / 10 μL of 'solutions respectively, for 14C-C10 (group A), and 1C- ciclopirox ( group C) . Experiment procedure: Day of Group A GTUDO C Study washing dose sample washing sample 0 1 D D 2 w D w D 3 w D C w D C 4 w D D 5 w D w D 6 w D C w D C 7 W D W D 8 W D W D 9 W D C W D C 10 W D W D 11 W D W D 12 W D C W D C 13 W D w D 14 W D w D 15 W C, N w C, N W = once a day before dosing (9 - 10 AM). D = once a day (9 - 10 AM). C = change / sample cotton ball after surface washing before topical dosing. N = nail sampling. Washing procedure The surface washing was started in the morning 10 minutes before the next dosage, the surface of the nail was washed with swabs in one cycle, as follows: A swab moistened with absolute ethanol, then a swab moistened with absolute ethanol , then a swab moistened with 50% IVORY liquid soap, then a swab moistened with distilled water, then a final swab moistened with distilled water. The wash samples from each cycle of each nail were grouped and collected by breaking the swab in scintillation glass containers. Aliquots of 3.0 L of methanol were added to each vessel to extract test material. The radioactivity of each sample was measured in a liquid scintillation counter. Incubation system A diffusion cell of a Teflon chamber (PermeGear, Inc., Hellertown, PA) was used to hold each nail. To approximate physiological conditions, a cotton swab ball moistened with 0.1 mL of standard saline solution was placed in the chamber to serve as a nail bed and provide moisture for the nail plate. Every 3 days, 0.1 mL of normal saline solution was injected through the chamber inlet to keep the cotton ball moist. The nail plate was placed on a shelf inside the receiver (1.0 cm in diameter and 0.5 cm high). The ventral surface (inside) of the nail was placed face down and rested on the wet cotton ball. The cells were placed on a platform in a large glass support tank filled with saturated sodium phosphate solution to keep the cells at a constant humidity of 40%. Sampling instrument The nail sampling instrument has two parts, a nail sampling platform and a drill. The nail sampling platform consists of a copper nail carrier, three adjustments and a fingernail dust capture. The three settings allow movement in the vertical direction. The first coarse adjustment (at the top) was to change the copper cell and take dust samples from the catch. The other two (lower) settings were for the sampling process. The second thick adjustment allowed movement of 25 mm and the fine adjustment provides movement of 0.20 mm. Nail dust capture was placed between the copper cell and the cutter. The inner shape of the capture was inverted funnel and the end of the funnel is connected to a vacuum. By placing a circular paper filter inside the funnel, the nail dust samples were captured in the paper filter during the sampling process. Sampling procedure After finishing the incubation phase, the nail plate of the diffusion cell was transferred to a clean copper nail carrier during the sampling process. The nail plate was inverted so that the ventral surface (nail bed) is now face up and the dorsal (external) dosed surface face down. The copper claw carrier has an opening while sitting on the top of the platform. When the sampling process starts, the coarse adjustment is adjusted to move the position of the platform until the nail plate is just touching the tip of the cutter. Then the drill is turned on. and the fine adjustment was turned to push the platform closer to the drill, removing a sample of nail center. After the above procedure, approximately 0.40-0.50 mm depth and 7.9 mm diameter of powdered nail samples were collected from the center of the ventral surface (nail bed) of the nail. Nail samples were collected in a scintillation glass container and weighed. 5.0 mL aliquots of Packard soluene-350 (Packard Instrument Company, Meriden, CT) to the scintillation vessel to dissolve the powder. The top, middle and back layers of the center of the nail, including the dose application area, were cut with the same diameter as the sampling area and then placed in a scintillation glass container with 5.0 mL of packard soluene-350. The rest of the nail was also placed in a scintillation glass container with 5.0 mL of packue soluene-350. The amount of nail sample removed was measured by the difference in weight of the nail plate before and after drilling and collecting the center of the powder. Measurement of radioactivity All radioactivity measurements were carried out with a Liquid Scintillation Counter Model 1500 (Packard Instrument Company, Downer Grove, IL). The meter was audited for accuracy using sealed samples of extinguished and non-extinguished standards as detailed in the instrument manual. The counting efficiency 1C is equal to or greater than 95%. All nail samples were pre-treated with packard soluene-350 were incubated at 40 ° C for 48 hours followed by the addition of 10 mL of scintillation cocktail (HIONIC-FLUOR, Packard Instrument Company, Meriden, CT). Other samples (standard dose, surface wash and bed material) were mixed directly with Universal ES scintillation cocktail (ICN Biomedicals, Costa Mesa, CA). Test samples and background checks were counted for 3 minutes each for radioactivity. Data analysis All sample counts (expressed as dpm) were transcribed by hand into a computer spreadsheet (Microsoft Excel). The average and individual amount (± SD) of chemical test equivalent in nails, bed material and wash samples are presented as dpm, μCi, percentage of administered dose and mg equivalent at each time point. The concentration of labeled 14C test chemicals was calculated from the value based on specific activity of each test chemical [1C]. The concentration information of test chemical not labeled in the topical formulation was obtained from the manufacturers. The total concentration of test chemical equivalent is the sum of the concentration of test chemical labeled 14C and the concentration of unlabeled test chemical. The value of the total amount of the test chemical equivalent in each nail sample was calculated from those values based on radioactivity of the sample and the ratio of test chemical equivalent total mg and radioactivity of the test chemical. The data were also normalized by dividing them with the weight of the sample. The level of significance of nail samples from each two groups was analyzed by student t-test. RESULTS Characteristics of nail samples The thickness of the complete nail plate, the depth of the ventral surface core sample removed by the cutter, the percentage of the thickness of the complete nail were collected for both groups (group A and group C). and the present weight of the nail powder sample. No statistical difference was found between two groups (P >; 0.05). Equivalent CIO and cyclopirox normalized in weight in nail Figure 3 shows equivalent of standardized drugs summarized in each part (layer) of the nail samples. After normalizing the weight, the concentration of the CIO equivalent in dorsal / intermediate center, ventral / intermediate center and rest of nail samples was significantly higher than the equivalent of ciclopirox (p = 0.002).

CIO equivalent and cyclopirox in cotton ball nail support bed Figure 4 shows equivalent CIO and cyclopirox summarized in cotton ball samples of support bed.

Similar to the normalization of weight the CIO equivalent in the nail plate samples, the absolute amount of CIO equivalent per sample of cotton ball in group A (after 14 days of dosing) was significantly higher than that of ciclopirox in group C (p <0.004). The '0 difference between these two test chemicals was 250 times. Mass balance of radioactivity of [1 C] - CIO and [1 C] -Cyclopirox after 14 days treatment Table 5 shows recovery of summarized radioactivity of washing, nail samples and ball samples of the support bed cotton. The cumulative radioactivity recoveries of carbon-14 were 88 ± 9.21, and 89 ± 1.56 percent of dose applied in group A, and group C, respectively. He was counted 88% of the radiolabelled material. 20 CONCLUSION In this study, penetration velocity of [14C] -C10 in topical formulation Anacor and [14C] - ciclopirox (8% w / w in commercial varnish) in human nail was studied with four different dosages and washing methods. ^ The results show that much more [14C] -C10 penetrates the deepest parts of the nail when purchased with [1C] -cyclopirox. Tables 3 and 4 show that the amount of [1C] -C10 equivalent in ventral / intermediate center of the nail layer and support bed of 5 cotton balls in group A was statistically higher (p = 0.002) than in Group C after a 14-day dosing period. Example 19 Determination of CIO Penetration in Human Nail '0 The objective of the current study was to evaluate and compare percutaneous absorption of CIO in a single carrier using MedPharm's TurChub® model (see http://www.medpharm.co.uk; specifically http://www.medpharm.co.uk/downloads/ 15 skin% 20and 2Onail 20dec% 202003.pdf; seen February 14, 2006), in a large-scale experiment. Six replicates that included IOC were carried out and formulations Y (8% ciclopirox p / p in commercial varnish) and Z (Loceril, 5% amorolfine p / v in commercial varnish) were used as the formulations of The following materials were used in these experiments.These materials were used without any modification.A dose of 40 μL / cm2 of the "50:50 CIO test of propylene glycol: ethyl acetate to a full-thickness nail sample every day for a total duration of five days .. Both reference formulations were also applied in the same dose." TurChub® Experimental Zone Placebo inhibition, carrier CIO test article and reference formulations Y and Z were evaluated during their inhibition of growth of Trichophi ton rubrum (T. rubrum) after penetration through a full-thickness human nail using a measuring zone of inhibition Evaluation of formulation efficacy Figures 5-9 show the results obtained from the TurnChub zone of inhibition tests.It can be seen that CIO is a potent antifungal agent, which can penetrate through a full-thickness nail for extract its effect against the target organism T. rubrum No zones of inhibition were observed with reference to the Y and Z formulations or with the placebo for CIO The experiment using CIO was repeated a second time to confirm the result and it can be observed in figures 6 and 7 that CIO shows areas of inhibition of 100%, 67%, 46%, 57%, 38% and 71% in the first experiment and 74%, 86%, 100%, 82%, 100% and 84% in the second experiment. The measurement was taken from the nail to the first observed growth point. From the results obtained using the MedPharm TurChub inhibition zone assay as an evaluation system, the CIO test article was found to be an antifungal agent potent and demonstrated superior results against commercial reference formulations Y and Z. From these experiments it appears that the compound permeates through a full-thickness nail barrier to exhibit antifungal activity. Example 20 Determination of CIO Penetration in the Human Nail: Response to Dose The optimal dose response scale for penetration into the human nail was determined to be between 1% and 15%. Experiments to determine the response to optimal dose were carried out as follows. Tests were carried out at different test concentrations on nails derived from the same corpse. The nails of the corpse were hydrated during the night, they were cut into 4 equal sized squares and placed on individual poloxomer supports. The test articles were formulated in a 1%, 2.5%, 5%, 7.5%, 10% and 15% w / v varnish. A dose of 40 μL / cm2 was applied to the center of the nail piece and the nails were left for 24 hrs. The nails were removed from the poloxomer support. The poloxomer support was analyzed for quantity of compound using LC / MS / MS.

Example 21 Preparation of pyridinyloxaboroles 21a. Metalation and Boronylation To a solution of 3-bromo-4-hydroxymethylpyridine (10.7 mmol) and B (OMe) 3 (2.73 mL, 11.9 mmol) in anhydrous THF (20 mL) at -78 ° C under nitrogen was added by dripping n-BuLi (13.6 L, 21.8 mmol). Then the cooling bath was removed. The mixture was gradually heated with stirring for 30 min and then stirred with a water bath for 2 h. Then brine was added and the pH was adjusted to 7 using 6N HCl. The mixture was washed with THF (x2) and the aqueous layer (containing the product) was evaporated to dryness. The residue was washed with THF and the product was extracted into ethanol (x2). The ethanol was removed under vacuum, water was added to the residue and it was removed in vacuo. Toluene was added and removed under vacuum. The resulting residue was triturated with diethyl ether and the product was collected by filtration to provide C12. 21b. 7 -Hydroxy -2, 1-oxaborolane [5, 4-c] pyridine [[1, 2] oxaborolo [3, 4-c] pyridin-l (3H) -ol] (C12) ^ -RMN (300 MHz, DMSO-d6): d ppm 5.00 (s, 2H), 7.45 (d, J = 5.0 Hz, 1H), 8.57 (d, J = 5.3 Hz, 1H), 8.91 (s, 1H), 9. 57 (s, 1H). ESI-MS n / z 134 (M-H) -, C6H6BN02 = 135.

EXAMPLE 22 Cyclic borinic esters Additional compounds can be produced by methods described herein. In selecting the appropriate starting material such as 1 or 3, Examples 1-7 can be used to formulate the following compounds. Melting point characterization is provided when available for these compounds. 22. Resul tadoe Analysis data are provided below for exemplary compounds of structure I. 22a 2- (1-Hydroxy-l, 3-dihydrobenzo [c] [1,2] oxaborol-5-yloxp ethyl acetate (C41) P.F. 134-137 ° C. Exemplary starting material: 2- (4-bromo-3- (hydroxymethyl) phenoxy) ethyl acetate. 22b 2- (1-Hydroxy-l, 3-dihydrobenzo [c] [1, 2] oxaborol-5-yloxy) acetic acid (C42) H "A O > or c P.F. 163-166 ° C Exemplary starting material: 2- (4-bromo-3- (hydroxymethyl) phenoxy) ethyl acetate The title compound is obtained after saponification of the corresponding ester. 22c 6- (thiophen-2-ylthio) benzo [c] [1,2] oxaborol-1 (3H) -ol (C43) P.F. 99-104 ° C. Exemplary starting material: (2-bromo-4- (thiophen-2-ylthio) phenyl) methanol. 22d 6- (4- fluoro-phenylthio) benzo [c] [1, 2] ox borol-l [3H) -ol (C44) -OH xys ?? P.F. 135-138 ° C. Exemplary starting material: (2-bromo-4- (4-fluorophenylthio) phenyl) methanol. 22e l- (3- ((l-hydroxy-1,3-dihydrobenzo [c] [1, 2] oxaborol-5-yloxy) methyl) phenyl) pentan-l-one P.F. 96-98 ° C. Exemplary starting material: l- (3- ((4-bromo-3- (hydroxymethyl) phenoxy) ethyl) phenyl) pentan-1-one. 22f 2- (1-Hydroxy-1,3-dihydrobenzo [c] [1,2] oxaborol-5-yloxy) -1- (piperidin-1-yl) ethanone (C46) P.F. 158-163 ° C. Exemplary starting material: 2- (4-bromo-3- (hydroxymethyl) phenoxy) -1- (piperidin-1-yl) ethanone. 22g 2- (1-hydroxy-1,3-dihydrobenzo [c] [1,2] oxaborol-5-yloxy) -1- (4- (pyrimidin-2-yl) piperazin-1-yl) ethanone (C47) 10567] P.F. 190-195 ° C. Ejepplar starting material: 2- (4-bramo-3- (hydroxymethyl) phenoxy) -1- (4- (pyrimidin-2-yl) piperazin-1-yl) ethanone. 22h 6- (4- (pyridin-2-yl) piper azin-1-yl) benzo [c] [1,2] oxaborol -1- (3H) -ol (C48) P.F. 135-138 ° C. Exemplary starting material: (2-bromo-4- (4- (pyridin-2-yl) piperazin-1-yl) phenyl) methanol. 22i 6-nitrobenzo [c] [1, 2] oxaborol -1 (3H) -ol (C49) P.F. 163-171 ° C. Exemplary starting material: benzo [c] [1,2] oxaborol-1 (3H) -ol. See JACS 82, 2172, 1960 for preparation. 22 j 6-aminobenzo [c] [1, 2] oxaborol -1 (3H) -ol (C50) OH H! NW P.F. 145-148 ° C. Exemplary starting material: 6-nitrobenzotc] [1, 2] oxaborol-1 (3H) -ol. 22k 6- (dimethylamino) benzo [c] [1,2] oxaborol-l (3H) -ol P.F. 120-123 ° C. Exemplary starting material: 6-aminobenzo [c] [1,2] oxaborol-1 (3H) -ol. 221 N- (1-hydroxy-1,3-dihydrobenzo [c] [1,2] oxaborol-6-yl) benzamide (C52) P.F. 186-193 ° C. Exemplary starting material: 6-aminobenzo [c] [1, 2] oxaborol-l (3H) -ol. 22m 6- (4-phenylpiperazin-1-yl) benzo [c] [1, 2] oxaborol-1 (3H) -ol (C53) P.F. 159-161 ° C. Exemplary starting material: (2-bromo-4- (4-phenylpiperazin-1-yl) phenyl) ethanol. 22o 6- (lH-indol-1 il) 'benzo [c] [1,2] oxaborol -1 (3H) -ol (C55) P.F. 135-140 ° C. Exemplary starting material: (2-bromo-4- (lH-indol-1-yl) phenyl) methanol. 22p 6-morpholinobenzo [c] [l, 21 -oxaborol-l (3H) -ol (C56) P.F. 128-132 ° C. Exemplary starting material: (2-bromo-4-morpholinophenyl) methanol. 22q 6- (1-hydroxy-l, 3-dihydrobenzo [c] [1, 2] oxaborol-5-i 1 oxy) nor cotinone tri 1 or (C57) OH NC? N Os P.F. 193-198 ° C. Exemplary starting material: 6- (4-bromo-3- (hydroxymethyl) phenoxy) nicotinonitrile. 22r 5-fluoro-6-nitrobenzo [c] [1, 2] oxaborol -1 (3H) -ol P.F. 162-167 ° C. Exemplary starting material: 5-fluorobenzo [c] [1,2] oxaborol-1 (3H) -ol. 22s 5-bromo-6- (hydroxymethyl) benzo [c] [1, 2] oxaborol -l (3H) -ol (C59) P.F. > 257 ° C. Exemplary starting material: (2,5-dibromo-4- (methoxymethyl) phenyl) methanol. 22t 3, 7-dihydro-l, 5-dihydroxy-lH, 3H-Benzo [l, 2-c: 4, 5-c '] bie [1,2] oxaborol (C60) . P.F. > 250 ° C. Exemplary starting material: (2,5-dibromo-1,4-phenylene) dimethanol. 22u 1- (1-hydroxy-1,3-dihydrobenzo [c] [1,2] oxaborol-6-yl) -3-phenylurea (C61) P.F. 213-215 ° C. Exemplary starting material: 6-aminobenzo [c] [1, 2] oxaborol-1 (3H) -ol. 22v N- (1-hydroxy-l, 3-dihydrobenzo [c] [1,2] oxaborol-6-yl) benzeneulfonamide (C62) P.F. 175-184 ° C. Exemplary starting material: 6-aminobenzo [c] [1, 2] oxaborol-1 (3H) -ol. 22w N- (1-hydroxy-1,3-dihydrobenzo [c] [1,2] oxaborol-6-yl) acetamide (C63) P.F. 176-185 ° C. Exemplary starting material: 6-aminobenzo [c] [1, 2] oxaborol-1 (3H) -ol. 22x 7- (hydroxymethyl) benzo [c] [1,2] oxaborol-l (3H) -ol (C64) P.F. 241-250 ° C. Exemplary starting material: (2-bromo-1,3-phenylene) dimethanol. 22 and 7-methylbenzo [c] [1, 2] oxaborol -1 (3H) -ol (C65) P.F. 107-111 ° C. Exemplary starting material: (2-bromo-3-methylphenyl) methanol. 22z 6- (3- (phenylthio) -lH-indol-1-yl) benzo [c] [1,2] oxaborol-1 (3H) -ol (C66) P.F. 159-163 ° C. Exemplary starting material: (2-bromo-4- (3- (phenylthio) -lH-indol-1-yl) phenyl) methanol. 22aa 3- (1- (1-hydroxy-l, 3-dihydrobenzo [c] [1,2] oxaborol -6-yl) -1H-indol-3-yl thio) propanone tri 1 or (C67) p.F. 135-141 ° C. Exemplary starting material: 3- (1- (3-bromo-4- (hydroxymethyl) phenyl) -lH-indol-3-ylthio) propanenitrile. 22bb 6- (5-methoxy-1 H -indole-1-yl) benzo [c] [1, 2] oxaborol -1 (3H) -ol (C68) P.F. 120-124 ° C. Exemplary starting material: (2-bromo-4- (5-methoxy-1H-indol-1-yl) phenyl) methanol. 22cc 5,6-methylenedioxybenzo [c] [1,2] oxaborol -1 (3H) -ol. (C69) P.F. 185-189 ° C. Exemplary starting material: (6-bromobenzo [d] [1, 3] dioxol-5-yl) methanol. 22dd 6-amino-5 f luorobenzo [c] [1, 2] oxaborol -1 (3H) -ol P.F. 142-145 ° C. Exemplary starting material: 6-nitro-5-fluorobenzo [c] [1, 2] oxaborol-l (3H) -ol. 22ee 6- (benzylamino) -5-f luorobenzo [c] [1, 2] oxaborol-1 (3H) -ol (C71) P.F. 159-164 ° C. Exemplary starting material: 6-amino-5-fluorobenzote] [1,2] oxaborol-l (3H) -ol. 22 ff 6- (5-methoxy-3- (phenylthio) -lH-indol-1-yl) benzo [c] [1,2] oxaborol -1 (3H) -ol (C72) P.F. 135-141 ° C. Exemplary starting material: (2-bromo-4- (5-methoxy-3- (phenylthio) -lH-indol-1-yl) phenyl) methanol. 22gg 3- (1- (1-hydroxy-1, 3-dihydrobenzo [c] [1,2] oxaborol-6-yl) -5-methoxy-lH-indol-3-ylthio) propane trilene (C73) P.F. 149-154 ° C. Exemplary starting material: 3- (1- (3-bromo-4- (hydroxymethyl) phenyl) -5-methoxy-1H-indol-3-ylthio) propanenitrile. 22hh 4- (1-Hydroxy-1,3-dihydrobenzo [c] [1,2] oxaborol-7-yloxy) benzoni trilo (C74) P.F. 148-153 °. Exemplary starting material: 4- (2-bromo-3- (hydroxymethyl) phenoxy) benzonitrile. 22ii 6- (5-chloro-lH-indol-l-yl) benzo [c] [1,2] oxaborol-1 (3H) -ol (C75) P.F. 149-154 ° C. Exemplary starting material: (2-bromo-4- (5-chloro-lH-indol-l-yl) phenyl) methanol. 22 jj 3- (5-chloro-l- (1-hydroxy-l, 3-dihydrobenzo [c] [1, 2] oxaborol-6-yl) -lH-indol-3-ylthio) propanenitrile (C76) P.F. > 225 exemplary starting material: 3- (1- (3-bromo-4- (hydroxymethyl) phenyl) -5-chloro-lH-indol-3-ylthio) propanenitrile. 22kk 6- (benzylanzino) benzo [c] [1,2] oxaborol -1 (3H) - .F. 126-133 ° C. Exemplary starting material: 6-aminobenzotc] [1,2] oxaborol-1 (3H) -ol. 2211 6- (dibenzylamino) benzo [c] [1, 2] oxaborol -1 (3H) -ol P.F. 115-123 ° C. Exemplary starting material: 6-aminobenzo [e] [1, 2] oxaborol-1 (3H) -ol 22mm 7- (4- (1H-tetrazol-5-yl) phenoxy) benzo [c] [1, 2] oxaborol -1 (3H) -ol (C19) P.F. decomposition at 215 ° C. Exemplary starting material: 4- (1-hydroxy-1,3-dihydrobenzo [c] [1,2] oxaborol-7-yloxy) benzonitrile. 22nn 6- (5-chloro-3- (phenylthio) -lH-indol-1-yl) benzo [c] [1, 2] oxaborol-1 (3H) -ol (C80) P.F. 145-151 ° C. Exemplary starting material: (2-bromo-4- (5-chloro-3- (phenylthio) -lH-indol-1-yl) phenyl) methanol. 22pp 6- (4- (Pyrimidin-2-yl) piperazin-1-yl) benzo [c] [1,2] oxaborol-1 (3H) -ol (C82) P.F. NA ° C. Exemplary starting material: (2-bromo-4- (4- (pyrimidin-2-yl) piperazin-1-yl) phenyl) methanol. 22qq 7- (benzyloxy) benzo [c] [1, 2] oxaborol -1 [3H) -ol (C83) P.F. NA ° C. Exemplary starting material: (3- (benzyloxy) -2-bromophenyl) methanol. 22rr 4- (1-Hydroxy-1,3-dihydrobenzo [c] [1, 2] oxaborol-6-ylthio) pyridinium chloride (C84) OH P.F. NA ° C. Exemplary starting material: (2-bromo-4- (pyridin-4-ylthio) phenyl) methanol. 22ee 6- (pyridin-2-yl thio) benzo [c] [1, 2] oxaborol -l (3H) -ol (C85) OH P.F. NA ° C. Exemplary starting materials: (2-bromo-4- (pyridin-2-ylthio) phenyl) methanol. 22tt 7-f luorobenzo [c] [1, 2] oxaborol -1 (3H) -ol (C86) P.F. 120-124 ° C. Exemplary starting material: (2-bromo-3-fluorophenyl) methanol. 22uu 6- (4- (trifluoromethyl) phenoxy) benzo [c] [1, 2] oxaborol -1 (3H) -ol (C87) P.F. 98-105 ° C. Exemplary starting material: (2-bromo-4- (4- (trifluoromethyl) phenoxy) phenyl) methanol. 22w 6- (4-chlorofenylthio) benzo [c] [1, 2] oxaborol -1 (3H) ol (C88) P.F. 157-161 ° C. Exemplary starting material: (2-bromo-4- (4-chlorophenylthio) phenyl) methanol. 22ww 6- (4-chlorophenyleneulfinyl) benzo [c] [1,2] oxaborol- P.F. 154-161 ° C. Exemplary starting material: 6- (4-chlorophenylthio) benzo [c] [1,2] oxaborol-1 (3H) -ol. 22xx 6- (4-chlorophenylene fonyl) benzo [c] [1,2] oxo borol- 1 (3H) -ol (C90) p.F. 157-163 ° C. Exemplary starting material: 6- (4-chlorophenylthio) enzo [c] [1,2] oxaborol-1 (3H) -ol. 22yy N- (1-hydroxy-1,3-dihydrobenzo [c] [1, 2] oxaborol-5-yl) -N- (phenylenedyl) benzeneulfonamide (C91) P.F. 142-152 ° C. Exemplary starting material: N- (4-bromo-3- (hydroxymethyl) phenyl) -N- (phenylsulfonyl) benzenesulfonamide. 22zz 6- (4- (trrif luoromethyl) phenyl thio) benzo [c] [1,2] oxaborol -1 (3H) -ol (C92) P.F. 111-113 ° C. Exemplary starting material: (2-bromo-4- (4- (trifluoromethyl) phenylthio) phenyl) methanol. 22aaa 6- (4- (trif'loromethyl) f-enyl eulfinyl) benzo [c] [1,2] oxaborol -1 (3H) -ol (C93) P.F. 79-88 ° C. Exemplary starting material: 6- (4- (trifluoromethyl) phenylthio) benzo [c] [1,2] oxaborol-l (3H) -ol. 22bbb 6- (4- (methylthio) phenylthio) benzo [c] [1, 2] oxaborol -1 (3H) -ol (C94) P.F. 117-120 ° C. Exemplary starting material: (2-bromo-4- (4- (methylthio) phenylthio) phenyl) methanol. 22ccc 6- (p-tolylthio) benzo [c] [1,2] oxaborol -1 (3H) -ol (C95) P.F. 139-144 ° C. Exemplary starting material: (2-bromo-4- (p-tolylthio) phenyl) methanol. 22ddd 3- ((1-hydroxy-l, 3-dihydrobenzo [c] [1, 2] oxaborol-5-yloxy) methyl) benzonitrile (C96) P.F. 147-150 ° C. Exemplary starting material: 3- ((4-bromo-3- (hydroxymethyl) phenoxy) methyl) benzonitrile. Example 23 Alternative preparation of 4 from 3 was equipped with a 3-neck flask of 22.0 L with a stirring motor, N2 inlet, addition funnel, heating mantle and condenser. The flask was charged with 3500 g (17.1 mol) of 2-bromo-5-fluorobenzyl alcohol followed by the addition of 3556 g of tetrahydrofuran and 16.4 g (0.17 mol) of methanesulfonic acid. Then, 400 g (4.7 mol) of 3,4-dihydro-2H-pyran was added at 10 ° C. This stage is exothermic in this way you should not do additional charges until you decrease exothermic. The temperature was increased to 27 ° C, stirred for 15 minutes and then charged with 400 g (4.7 mol) of 3,4-dihydro-2H-pyran at 24 ° C. Again, the temperature was increased (24 ° C to 38 ° C). The mixture was stirred for 15 minutes. Once the exotherm decreased, the flask was reloaded with 400g (4.7 mol) of 3,4-dihydro-2H-pyran at 35 ° C. The temperature was again increased to 47 ° C for a period of 20 minutes. Once the exotherm decreased, the mixture was stirred for 15 minutes. Finally, the remaining 400 g (4.7 mol) of 3,4-dihydro-2H-pyran was added at 44 ° C. The temperature was increased to 51 ° C. After stirring for one hour, a sample was removed to verify the removal of starting material. When the reaction was finished, the contents were cooled to 20 ± 5 ° C.

Example 24 CJHMBGFOJ 12WF, g? F C14H20BFO4 5 PeSo Mol.:289.14 Weight Mol .: 313.45 Weight Mo: 282 12 Alternative preparation of 5 from 4 To a 22.0 L three-necked flask equipped with a stirring motor, N2 inlet, addition funnel, cooling bath and condenser were charged 436 g (17.96 mol) of ** magnesium curves. HE then added 5334 g of tetrahydrofuran followed by 291 g (0.51 mol) of diisobutylaluminum hydride (DIBAL) (25% w) in toluene. The mixture was stirred for 60 min at 20 ± 5 ° C. Some evolution of gas was observed. Then, 260-430 g -3-5% (by weight if the solution of 4 was dripped into tanks) of 4 in THF was added. The mixture was stirred for 15-30 minutes, during which a slight exothermic could be observed (? T = 10-15 ° C). Once the exothermic was observed, the reaction mixture was cooled to 5 ± 5 ° C. To this mixture, the 8.22-8.39 kg of remaining 4 in THF was added at a rate such that the temperature was kept below 30 ° C (t = 3h). The reaction was stirred at 20-25 ° C ™ for 30 minutes, during which time an aliquot was removed, quenched with 3N HCl (10 mL), and analyzed. At the end, the contents were cooled to -25 ± 5 ° C. A solution of trimethyl borate in THF was prepared by mixing 2665 g (25.7 mol) of trimethyl borate and 6666 g of ^ Tetrahydrofuran. This solution can be prepared in a stirred tank. Then, the 9331 g of trimethyl borate in THF was added at a rate so that the temperature was maintained between -35 and -20 ° C (t = 2.5h). The mixture became very thick so THF was added. After stirring at -25 ± 5 ° C for 10 min, 50 mL of aliquot was removed, rapidly quenched with 25 mL of 3N HCl, and subjected to CoR. Stirring was continued at -25 ± 5 ° C for 1 hour, and then the mixture was allowed to warm to room temperature, where it was stirred for at least 12 hours. Two samples were extracted (one at 6 hours and the other at 12 hours). Reected: ^ -RMN (300 MHz, DMSO-d6) 5 (ppm) 1.45-1.75 (m, 6H), 3. 53 (s, 6H), 3.45 (m, 1H), 3.75 (m, 1H), 4.69 (t, J = 3 Hz, 1H), 4.97 (d, J = 14.1 Hz, 1H), 5.14 (d, J = 14.1 Hz, 1H), 7.03 ((td, J8.4, 2.7 Hz, 1H), 7.24 (dd, J = 10.8, 2.1 Hz, 1H), 7.89 (t, J = 7.8 Hz, 1H), 8.76 (s, 1H) Example 25 Alternative preparation of I from 5 Mol Weight: 282.12 5.3 kg of USP water was added to the above reaction mixture. After stirring for 30 minutes, the mixture was charged with 5.3 kg of acetic acid. Gas evolution was observed. After stirring for 30 minutes, an aliquot was removed for analysis. The mixture was then heated to reflux for 36-48 hours. During the reflux period, 12-13 L of THF were removed. When the reaction was completed, the contents were cooled by the reactor to < 40 ° C when placing a cover and when loading 10.5 kg of USP water. THF was removed until no distillate remained. The contents of the reactor were transferred to Rosenmund filter dryer and allowed to cool to 20 ± 5 ° C. The reactor was rinsed with water, filtered and then washed again with 10.5 kg of USP water. The flask was charged with 10.5 kg of 10% ACN in water (v / v) and stirred for 1 hour. After filtering, the cake was washed with 10.5 kg of 10% ACN in water (v / v), and then loaded with 10.5 kg of 10% ACN in water (v / v). The contents were stirred for 1 hour. The contents were subsequently washed with 10.5 kg of USP water, charged with 7.0 L of 5% methyl t-butyl ether (MTBE) / Heptane (v / v), stirred for 1 hour, filtered, loaded with 7.0 L of 5% MTBE / Heptans (v / v) and again stirred for 1 hour. After filtering, the contents were again charged with 7.0 L of heptane and filtered. The solids were dried to < 45 ° C to constant weight. The toluene: heptane 75:25 solids were recrystallized. Example 26 Alternative preparation of CIO intermediary OH [[4-Fluoro-2- [(tetrahydro-2H-pyran-2-yl) oxy] methyl] phenyl] boronic acid 2-Bromo-5-fluorobenzyl alcohol (5g), 24.4mmol) was dissolved in dichloromethane (100mL). To this solution was added 3,4-dihydro-2H-pyran (3.2mL, 36.6mmol) and (1S) - (+) - 10-camphorsulfonic acid (117mg, 0.5mmol) and stirred at room temperature under nitrogen during 4 hours. Saturated sodium bicarbonate was added to quickly quench the reaction. It was extracted using dichloromethane and the organic layer was washed with brine and dried over sodium sulfate, then concentrated in vacuo to give [1-bromo-4-fluoro-6- [(tetrahydro-2H-pyran-2-yl) oxy] methyl] benzene as a colorless oil (7g, 100%). [1-Bromo-4-fluoro-6- [(tetrahydro-2H-pyran-2-yl) oxy] ethyl] benzene (1.8g, 6.2mmol) was dissolved in THF and cooled to -78 ° C under nitrogen. To this solution was added n-butyllithium (1.6M in hexane) (6.2mL, 9.3mmol) per drop, then triisopropyl borate (2.2mL, 9.3mmol) was added. The mixture was slowly warmed to room temperature and stirred for 3 h. Water was added to rapidly quench the reaction. It was then extracted using ethyl acetate, washed with brine, dried over sodium sulfate and concentrated in vacuo. After column chromatography (silica gel; hexane: ethyl acetate = 4: 2: 1) purification, [[4-Fluoro-2- [(tetrahydro-2H-pyran-2-yl) oxy] methyl] phenyl] boronic acid was obtained as a white solid ( l.lg, 70%). Reected: ^ -RMN (300 MHz, DMSO-d6) d (ppm) 1.45-1.74 (m, 6H), 3. 44 (m, 1H), 3.75 (m, 1H), 4.58 (d, J = 13.2 Hz, 1H), 4.64 (t, J = 3 Hz, 1H), 4.79 (d, J = 13.2 Hz, 1H), 7.03 (td, J = 8.4, 2.7 Hz, 1H), 7.13 (dd, J = 10.8, 2.7 Hz, 1H), 7.50 (t, J = 6.9 Hz, 1H). Example 27 Alternative preparation of CIO Broker This [[4-fluoro-2-f (tetrahydro-2H-pyran-2-yl) oxy] met yl] phenyl] boronic acid [[4-Fluoro-6- [(tetrahydro-2H-pyran-2-yl)] oxy] methyl] phenyl] boronic acid (100 mg) was dissolved in dry methanol, the solution was repeatedly distilled to remove water. The resulting residue was immediately characterized by NMR and found to be a mixture containing dimethyl ester and monomethyl ester. [[4-fluoro-2- [(tetrahydro-2H-pyran-2-yl) oxy] methyl] phenyl] boronic acid dimethyl ester. ^ -RMN (300 MHz, DMSO-d6) 6 (ppm) 1.45-1.75 (m, 6H), 3. 43 (s, 6H), 3.45 (m, 1H), 3.75 (m, 1H), 4.69 (t, J = 3 Hz, 1H), 4.97 (d, J = 14.1 Hz, 1H), 5.14 (d, J = 14.1 Hz, 1H), 7.03 ((td, J = 8.4, 2.7 Hz, 1H), 7.24 (dd, J = 10.8, 2.1 Hz, 1H), 7.89 (t, J = 7.8 Hz, 1H). of [[4-fluoro-6- [(tetrahydro-2H-pyran-2-yl) oxy] methyl] phenyl] oronic acid XH-NMR (300 MHz, DMSO-d6) d (ppm) 1.45-1.75 (m, 6H), 3.53 (s, 6H), 3.45 (m, 1H), 3.75 (m, 1H), 4.69 (t, J = 3 Hz, 1H), 4.97 (d, J = 14.1 Hz, 1H), 5.14 (d, J = 14.1 Hz, 1H), 7.03 ((td, J = 8.4, 2.7 Hz, 1H), 7.24 (dd, J10.8, 2.1 Hz, 1H), 7.89 (t, J = 7.8 Hz, 1H), 8.76 (s, 1H) Example 28 Alternative preparation of CIO Intermediary [(4-Fluoro-2-methoxymethoxymethyl) phenyl] boronic acid [1-Bromo-4-fluoro-6-methoxymethoxymethyl] benzene (525 mg, 2 mmol) was dissolved in THF and cooled to -78 ° C under nitrogen. To this solution was added n-butyllithium (1.6M in hexane) (1.5mL, 2.4mmol) by drip, then triisopropyl borate (0.7mL, 2.4mmol) was added. The mixture was slowly warmed to room temperature and stirred for 3 h. Water was added to rapidly quench the reaction. It was then extracted using ethyl acetate, washed with brine, dried over sodium sulfate and concentrated in vacuo. After recrystallization from hexane: ethyl acetate = 4: 1, [(4-fluoro-2-methoxymethoxymethyl) phenyl] boronic acid was obtained as a white solid (340 mg, 75%). X H-NMR (300 MHz, DMSO-d 6) d (ppm) 3.28 (s, 3 H), 4.70 (s, 2H), 5.02 (s, 2H), 7.04 (td, J = 9.0, 3.0 Hz, 1H), 7.23 (dd, J = ll.l, 2.4 Hz, 1H), 7.90 (t, J = 7.8 Hz, 1H). Example 29 Alternative preparation of intermediate C17 [[4- [4-Cyanophenoxy-2- [(tetrahydro-2H-pyran-2-yl) oxylmethyl] phenyl] boronic acid. 2-Bromo-5- (4-cyanophenoxy) benzyl alcohol (10.4g, 34.2 mmol) was dissolved. ) in dichloromethane (HOmL). To this solution was added 3,4-dihydro-2H-pyran (9.2mL, lOlmmol) and acid (IS) - (+) - 10-camphorsulfonic acid (156mg, 0.67mmol) and stirred at room temperature under nitrogen for 3h. . Methanesulfonic acid (50 μL, 0.77 mmol) was then added and the reaction was stirred overnight. Saturated sodium bicarbonate was added to quickly quench the reaction. It was extracted using ethyl acetate and the organic layer was washed with brine and dried over sodium sulfate, then concentrated in vacuo to give [1-bromo-4- (4-cyanophenoxy) -6- [(tetrahydro-2H- pyran-2-yl) oxy] methyl] benzene as a colorless oil (13.3g. cant.). [1-Bromo-4- (4-cyanophenoxy) -6- [(tetrahydro-2H-pyran-2-yl) oxy] methyl] benzene (13.3 g, 34.2 mmol) was dissolved in THF (100 mL), added triisopropyl borate (8.5 mL, 37 mmol) and the reaction was cooled to -78 ° C under nitrogen. To this solution was added n-butyllithium (1.6M in hexane) (22mL, 35.2mmol) per drop. The mixture was slowly warmed to room temperature and stirred overnight. THF was removed in vacuo and the residue was dissolved in ethyl acetate. It was then washed with water, brine, dried over sodium sulfate and concentrated in vacuo. After column chromatography (silica gel, hexane: ethyl acetate 2: 1) purification of a portion of [[4- (4-cyanophenoxy) -6- [(tetrahydro-2H-pyran-2-yl) oxy]] ] methyl] phenyl] boronic acid was obtained as a clear oil (500 mg, 4%).

Hi-NMR (300 MHz, DMSO-d6 + D20) d (ppm) 1. 35-1. 75 (m, 6H), 3.40 (m, 1H), 3.73 (m, 1H), 4.58 (d, J = 13.2 Hz, 1H), 4.59 (s, 1H), 4.77 (d, J = 12.7 Hz, 1H), 6.99 (dd, J = 8.1, 2.2 Hz, 1H), 7.05 (m, 3H), 7.54 (d, J "= 7.9 Hz, 1H), 7.81 (d, J = 8.8 Hz, 2H). [[4- (4-Pentanoylphenoxy) -6 - [(tetrahydro-2H-pyran-2-yl) oxy] methyl] phenyl] boronic acid was also isolated as a clear oil (500 mg, 4%). XH-NMR (300 MHz, DMSO-d6 + D20) d (ppm)), 0.85 (t, J = 7.5 Hz, 3H), 1.20-1.75 (m, 10H), 2.93 (t, J = 7.0 Hz, 2H), 3.42 (m, 1H), 3.70 (m, 1H), 4.58 (d, J = 12.8 Hz, 1H), 4.60 (s, 1H), 4.78 (d, J = 13 .2 Hz, 1H), 6.94 (d, J = 8.4 Hz, 1H), 7.03 (d, J = 8.4 Hz, 2H), 7.04 (s, 1H), 7.54 (d, J = 8.4 Hz, 1H), 7.96 ( d, J = 8.4 Hz, 2H). Example 30 Alternative preparation of intermediate Cll Dimethyl acid ether [[4- [4-cyano phenoxy] -2- [(tetrahydro-2H-pyran-2-yl) oxy] ethyl] phenyl] boronic acid Using the same method as in CIO Example IIE, a mixture was synthesized of mono- and dimethyl esters of [[4- (4-cyanophenoxy) -2- [(tetrahydro-2H-pyran-2-yl) oxy] methyl] phenyl] boronic acid. ^ -RMN (300 MHz, DMSO-d6) d (ppm) 1.35-1.80 (m, 6H), 3.40-3.50 (m, 7H), 3.60-3.70 (m, 1H), 4.43 (d, J = 12.7 Hz , 1H), 4.60-4.80 (m, 2H), 6.95-7.15 (m, 4H), 7.38 (d, J = 8.4 Hz, 1H), 7.80-7.90 (m, 2H). Monomethyl ether [[4- [4-cyano phenoxy] -6- [(tetrahydro-2H-pyran-2-yl) oxy] methyl] phenyl] boronic acid XH-NMR (300 MHz, DMS0-d6) d (ppm 1.35-1.80 (m, 6H), 3. 40-3.50 (m, 1H), 3.55 (s, 3H), 3.60-3.70 (m, 1H), 4.55 (d, J = 12.8 Hz, 1H), 4.60-4.80 (m, 2H), 6.95-7.15 ( m, 4H), 7.53 (d, J = 7.9 Hz, 1H), 7.80-7.90 (m, 2H), 8.77 (s, 1H).

Using the same method as above, a mixture of mono- and dimethyl esters of [[4- (4-pentanoylphenoxy) -2 - [(tetrahydro-2H-pyran-2-yl) oxy] methyl] phenyl] boronic acid was synthesized. .

Dimethyl acid ether [[4- (4-pentanoyl phenoxy) -2- [(tetrahydro-2H-pyran-2-yl) oxy] methyl] phenyl] boronic acid ^ -R (300 MHz, DMSO-de) d (ppm) 0.87 (t, J = 7.3 Hz, 3H), 1.25-1.80 (m, 10H), 2.94 (t, J = 7.3 Hz, 2H), 3.40-3.50 (m, 7H), 3.60-3.70 (m, 1H), 4.43 (d, J = 12.8 Hz, 1H), 4.60-4.80 (m, 2H), 6.90-7.10 (m, 4H), 7.36 (d, J = 7.9 Hz, 1H), 7.95-8.05 (m, 2H). Acid monomethyl ether [[4- (4-pentanoyl phenoxy) -6- [(tetrahydro-2H-pyran-2-yl) oxy] methyl] phenyl] boronic acid ^ • H-NMR (300 MHz, DMSO-d6) d (ppm) 0.87 (t, J = 7.3 Hz, 3H), 1.25-1.80 (m, 10H), 2.94 (t, J = 7.3 Hz, 2H), 3.40-3.50 (m, 1H), 3.55 (s, 3H), 3.60-3.70 (m, 1H), 4.55 (d, J = 12.8 Hz, 1H), 4.60-4.80 (m, 2H), 6.95-7.15 ( m, 4H), 7.52 (d, J = 7.9 Hz, 1H), 7.95-8.05 (m, 2H), 8.75 (s, 1H). Example 31 Alternative preparation of CIO Intermediary Alcohol Borate Intermediate Alcohol-Borate To a pre-registered RNM tube containing a solution of 2-bromo-5-fluorobenzyl alcohol (16 mg, 0.078 mmol) in CDC13 (0.75 mL) was injected with triisopropyl borate (0.036 mL) , 2 eq, 0.156 mmole) and the solution briefly sonicated for 30 seconds at room temperature. The 1 H NMR determination indicated that there were 74.3% moles of the desired alcohol-borate intermediate, 19.3% moles of an unknown intermediate and 6.3% moles of unreacted alcohol. Resulted: XH NMR (CDC13, 300 MHz) of (2-bromo-5-fluorobenzyl) diisopropyl borate: d = 7.45 (dd, J = 8.7 Hz, J = 5.1 Hz, 1H), 7.20 (dd, J = 9.6 Hz, J = 2.7 Hz, 1H), 6.84 (td, Jt = 8.1 Hz, Jd = 3.3 Hz, 1H), 4.84 (s, 2H), 4.44 (septet, J = 6.0 Hz, 2H), 1.18 (d, J = 6.0 Hz, 12H) ppm. XH NMR (CDC13, 300 MHz) from an unknown intermediate: d = 7.47-7.42 (1H, overlap with product peaks), 7.16 (dd, 1H, partially overlap with product peak), 6.91-6.81 (1H, overlaps with product peaks), 4.94 (s, 2H), and other unknown peaks due to overlap. * H NMR (CDC13, 300 MHz) of pre-registered 2-bromo-5-fluorobenzyl alcohol before mixing: < 5 = 7.48 (dd, J = 9.0 Hz, J = 5.4 Hz, 1H, overlap with product peaks after mixing with triisopropyl borate), 7.26 (dd, J = 9.3 Hz, J = 3.3 Hz, 1H, decreased intensity but resolved after mixing), 6.88 (td, Jc = 8.3 Hz, Jd = 3.0 Hz, 1H, overlap with product peaks after mixing), 4.71 (s, 211, CH2 intensity decreased but resolved after mixing), 2.04 (s, 1H, OH disappeared after mixing with triisopropyl borate) ppm. Example 32 Alternative preparation of intermediate Cll N M? The procedure described in Example III was followed for XH NMR characterization of the current alcohol-borate intermediate. The XH NMR determination indicated that there were 72.7% moles of the desired borate alcohol-borate intermediate of [2-bromo-5- (4-cyanophenoxy) benzyl] diisopropyl, 20.7% moles of an unknown intermediate and 6.5% moles of unreacted alcohol. 1 H NMR (CDC13, 300 MHz) of [2-bromo-5- (4-cyanophenoxy) benzyl] diisopropyl borate: d = 7.61 (d, J = 9.0 Hz, 2H), 7.52 (d, J = 8.4 Hz, 1H), 7.15 (d, J = 3.0 Hz, 1H), 7.03 (d, J = 8.7 Hz, 2H), 6.84 (dd, J = 8.7 Hz, J = 3.0 Hz, 1H), 4.85 (s, 2H) , 4.35 (septet, J = 6.1 Hz, 2H), 1.11 (d, J "6.1 Hz, 12H) ppm Example 33 Alternative preparation Q? > S X CT C < and The procedure described in Example III was followed for 1 H NMR characterization of the current alcohol-borate intermediate. XH NMR determination indicated that there were 73.5% moles of the desired borate alcohol-borate intermediate of [2-bromo-4- (4-chlorophenylthio) benzyl] diisopropyl, 20.2% moles of an unknown intermediate and 6.2% moles of unreacted alcohol. XH NMR (CDC13, 300 MHz) of [2-bromo-4- (4-chlorophenylthio) benzyl] diisopropyl borate: d = 7.48 (d, J = 1.8 Hz, 1H), 7.40 (d, J = 8.3 Hz, 1H), 7.27 (s, 4H), 7.25 (dd, J = 8.3 Hz, J = 1.8 Hz, 1H), 4.86 (s, 2H), 4.42 (septet, J = 6.3 Hz, 2H), 1.16 (d, J = 6.3 Hz, 12H) ppm. Example 34 Adenosine CIO Complex A mixture of 1,3-dihydro-5-fluoro-l-hydroxy-2, 1-benzoxazole (CIO, 0.76 g, 5 mmol), adenosine (1.34 g, 5 mmol) and sodium acetate (0.41 g, 5 mmol) ) in dry DMF (100 mL) was stirred at 100 ° C for 3 h under nitrogen atmosphere.

The homogeneous solution was rotatively evaporated at 50 ° C under high vacuum. The residue was mixed with methylene chloride, sonicated and filtered under nitrogen atmosphere to give the desired complex as a white solid which was pumped overnight (2.2 g, 100% yield). 1 H NMR indicated that there were 5.7% moles of unreacted adenosine, 5.5% moles of unreacted CIO, and the reaction conversion was more than 94% * H NMR (DMSO-de, 300 MHz): < 5 = 8.33 (s, 1H), 8.12 (s, 1H), 7. 35-7.14 (broad m, 1H), 7.29 (s, 2H), 6.80 (broad m, 1H), 6. 73 (d, J = 9.9 Hz, 1H), 5.99 (broad d, J = 2.1 Hz, 1H), 5.10 (very broad s, 1H), 4.71 (dd, J = 5.7 Hz, J = 3.9 Hz, 1H) , 4.51 (s, 2H), 4.42 (dd, J "= 6.3 Hz, J = 3.9 Hz, 1H), 4.07 (broad s, 1H), 3.64 (dd, J = 12 Hz, J = 3.6 Hz, 1H) and 3.52 (dd, J = 12 Hz, J = 5.1 Hz, 1H) ppn; P.F. : initiated smoothing at 115 ° C due to residual solvents, remained as softened solids and decomposition started at 230 ° C; CLAR: 91.8% in 220 nm (adenosine was 5.3%); MS: m / z = 423 (M-, ESI-), 392 (M-OfeOH, ESI +). Example 35 The procedure described above was adapted during the preparation of the title complex by replacing (CIO) with 5- (-cianofenoxi) -1,3-dihydro-l-hydroxy-2, 1-benzoxazole (C17, 1.25 g, 5 mmoles ). White solid product (2.7 g, 100% yield) was obtained after pumping overnight. XH NMR indicated that there was 3.5% moles of unreacted adenosine, 3.5% moles of unreacted C17, and the reaction conversion was more than 96%. X H NMR (EMSO-de, 300 MHz): d = 8.35 (s, 1H), 8.13 (s, 1H), 7.76 (d, J = 8.7 Hz, 2H), 7.45-7.36 (broad m, 1H), 7.29 (s, 2H), 7.00 (d, J = 8.7 Hz, 2H), 6.81 (broad m, 1H), 6.73 (s, 1H), 6.01 (broad s, 1H), 5.10 (s very broad, 1H), 4.73 (dd, J = 6.0 Hz, J = 3.9 Hz, 1H), 4.54 (s, 2H), 4.45 (dd, J = 6.0 Hz, J = 3.9 Hz, 1H), 4.09 (s applio, 1H), 3.65 (dd, J = 12 Hz, J = 3.3 Hz, 1H) and 3.54 (dd, J = 12 Hz, J = 4.8 Hz, 1H) ppm; P.F. : it started smoothing at 120 ° C due to residual solvents, it remained solid and smoothed and started decomposition at 230 ° C; HPLC: 92.1% at 220 nm (adenosine was 3.8%). Example 36 Adenosine Complex C28 The procedure for the synthesis of the complex of adenosine CIO was adapted for the preparation of the title complex when replacing (CIO) with 6-phenylthio-l, 3-dihydro-l-hydroxy-2, 1-benzoxabole (C28, 1.21 g, 5 mmoles). White solid product (2.8 g, 100% yield) was obtained after pumping overnight. 1 H NMR indicated that there was 5% moles of unreacted C28, and the reaction conversion was 95%. 1 HOUR NMR (DMSO-de, 300 MHz): d = 8.29 (s, 1H), 8.13 (s, 1H), 7.53 (broad s, 1H), 7.29 (s, 2H), 7.32-7.04 (m, 7H), 6.05-5.96 (broad m, 1H), 5.15 (s very broad, 1H), 4.73-4.70 (m, 1H), 4.58 (s, 2H), 4.46 (broad s, 1H), 4.12-4.03 (broad m, 1H), 3.63 (dd, J = 11.7 Hz, J = 3.3 Hz, 1H) and 3.52 (dd, J = 11.7 Hz, J = 4.8 Hz, 1H) ppm; P.F. : initiated softening at 110 ° C due to residual solvents, remained as a softened solid and decomposition started at 238 ° C. HPLC: 91.3% at 220 nm (adenosine was 3.8%). Example 37 Adenosine Complex C2 The procedure for the synthesis of the CÍO adenosine complex was adapted for the preparation of the title complex by replacing (CIO) with 1,3-dihydro-l-hydroxy-2, 1-benzoxazole (C2, 0.67 g, 5 mmol) . Solid cream product (2.18 g, 100% yield) was obtained after pumping overnight. 1 H NMR indicated that there was 4.5% moles of unreacted C 2, and the reaction conversion was more than 94%. 1 HOUR NMR (DMSO-de, 300 MHz): d = 8.33 (s, 1H), 8.13 (S, 1H), 7.42-7.20 (broad m, 1H), 7.30 (s, 2H), 7.03-6.94 (m, 3H) ), 6.02 (d, J = 3.6 Hz, 1H), 5.25 (s very broad, 1H), 4.73 (dd, J = 5.7 Hz, J = 4.2 Hz, 1H), 4.56 (s, 2H), 4.46 (dd) , J = 6.0 Hz, J = 3.9 Hz, 1H), 4.10 (broad q, J = 3.3 Hz, 1H), 3.66 (dd, J "= 12 Hz, J = 2.7 Hz, 1H) and 3.52 (dd, J "= 11.7 Hz, J = 4.8 Hz, 1H) ppm; P.F .: initiated smoothing at 115 ° C due to residual solvents, remained as a softened solid and decomposition started at 233 ° C. HPLC: 91.6% at 220 nm (adenosine was 5.9%). Example 38 Synthesis of methyl ß-D-ribofuranoside 5g of D-Ribose were dissolved in 100 ml of methanol and cooled to 0 ° C. 0.5mL of concentrated sulfuric acid was added and the solution was stored at -20 ° C for 48hrs. The solution was neutralized by passing it through a bed of sodium carbonate and evaporated in vacuo to a viscous oil. Crude material was purified on a silica column eluting with 10% methanol in ethyl acetate to yield 2.1 grof methyl β-D-ribofuranoside. XH NMR 300 MHz (DMSO-de) d 4.97-4.99 (d, J = 4.8 Hz, 1H), 4.76-4.79 (d, J = 6.6 Hz, 1H), 4.57-4.62 (m, 2H), 3.76-3.80 (m, 1H), 3.72-3.74 (m, 1H), 3.66-3.71 (m, 1H), 3.44-3.50 (m, 1H), 3.26-3.34 (m, 1H), 3.19 (s, 3H) Example 39 General procedure for complex formation 300mg of methyl ß-D-ribofuranoside was dissolved in 20 mL of dimethylformamide. To this solution was added 1 eq. of boronic ester and 0.5 eq. of finely powdered sodium carbonate. The reaction mixture was heated to 100 ° C and stirred for 3 hours then solvent was removed under vacuum. The residue was co-evaporated 2 times with ethyl acetate then sonicated in dichloromethane and filtered to yield an off-white solid.

Cryl Methylribose Complex XH NMR 300 MHz (DMSO-de) d 7.28 (bs, 1H), 6.68-6.77 (, 2H), 4.71 (s, 1H), 4.52-4.55 (m, 3H), 4.26-4.28 (d, J = 5.1 Hz, 1H), 4.17-4.19 (d, J = 5.7 Hz, 1H), 3.95-4.00 (t, J = 6.8 Hz, 1H), 3.31-3.36 (, 2H), 3.19 (s, 3H). Cll methylribose complex XH NMR 300 MHz (DMSO-d6) d 7.73-7.76 (d, J = 6.9 Hz, 2H), 7.38-7.41 (d, J = 7.8 Hz, 1H), 6.96-6.99 (d, J = 6.9 Hz, 2H ), 6.72-6.75 (d, J = 7.5 Hz, 1H), 6.68 (s, 1H), 4.70 (s, 1H), 4.49-4.51 (m, 3H), 4.23-4.25 (d, J = 5.4 Hz, 1H), 4.14-4.16 (d, J = 5.4 Hz, 1H), 3.95-3.98 (m, 1H), 3.22-3.26 (t, J = 6.0, 1H), 3.19 (s, 3H), 3.13-3.14 ( d, J = 2.1, 1H).

C2 methylribose complex XH NMR 300 MHz (DMSO-d6) d 7.31 (bs, 1H), 6.87-6.95 (m, 3H), 4.70 (s, 1H), 4.46-4.50 (m, 3H), 4.20-4.22 (d, J = 5.7, 1H), 4.12-4.14 (d, J = 6.0 Hz, 1H), 3.94-3.99 (t, J = 7.8 Hz, 1H), 3.30-3.34 (m, 2H), 3.19 (s, 3H). C28 Methylribose Complex XH NMR 300 MHz (DMSO-de) d 7.48 (bs, 1H), 7.21-7.26 (m, 2H), 7.05-7.12 (m, 4H), 6.98-7.01 (d, J = 7.8 Hz, 1H), 4.65 (s, 1H), 4.47-4.58 (m, 3H), 4.22-4.24 (d, J = 5.7 Hz, 1H), 4.13-4.15 (d, J = 6.0 Hz, 1H), 3.89-3.93 (t , J = 6.6 Hz, 1H), 3.28-3.32 (t, J = 6.5, 1H), 3.13-3.16 (m, 4H). Example 40 Mechanism of action The purpose of this study is to determine the mechanism of action (MOA) of CÍO in the fungus model Saccharomyces cerevieiae. 40. 1 Method The Saccharomycee cerevieiae haploid strain ATCC 201388 was used in the selection of CIO-resistant mutants. EMS-induced and spontaneous resistant mutants were isolated from YPD agar plates containing 4x, 8x, 16x MIC of CIO. All minimal inhibitory cranings (MIC) were determined using M27 NCCLS protocol with the exception of the use of YPD or synthetic defined medium. All yeast and molecular genetic manipulations were carried out essentially as described by Guthrie C, et al. , Methode in Enzymology, 350: Part B, (2002). 40.2 Reelected and Conclude A total of 11 CIE-resistant mutants of S. cerevieiae were isolated, all mutants were dominant and showed an 8- to 64-fold improvement in MIC for CÍO.

Additional characterization of these mutants showed that they were not resistant to several antifungals including amphotericin B, cerulenin, itraconazole, aculeacin A, terbinafine, tunicamycin, cyclopirox, cyclohexamide and ni komicin Z. The 11 mutations in the mutant resistant to CÍO were equated to residues of 9 amino acids in the CDC60 editing domain, the essential cytoplasmic leucyl-tRNA synthetase, one of 40 tRNA-aminoacyl synthetases in S. cerevisiae. Furthermore, strains of S. cerevisiae carrying multiple copies of CDC60 in a plasmid 2 were eight times more resistant to CIO. The combination of mutant and overexpression data predicts that CDC60 is the target for CIO. The fact that all mutations were present in the CDC60 editing domain indicates that CDC60 inhibits CIO by a novel mechanism. The lack of a genomic sequence of any genetic tool for Trichophi ton spp. It is difficult to study the mechanism of action of CIO in any Trichophi ton species, therefore, the model fungus was used Saccharomyces cerevisiae. 40.3 Materials and Methods 40.3a Chemicals, cepae and plasmids CIO (5-fluoro-l, 3-dihydro-l-hydroxy-2, l-benzoxazole, was obtained from Anacor Pharmaceuticals, Inc. (Palo Alto, CA, E.U.A.). All S. cerevisiae strains and ATCC plasmids (Manassas, VA, E.U.A.) were obtained. The Saccharomyces cerevisiae haploid strain ATCC201388 (MATa his3? L leu2? 0 metS? O ura3? 0) was used for the mutant gene, whereas ATCC 200901 (MATa leu2? 0 lye2? 0 ura3? 0) was used to pair with mutants resistant to CÍO to determine genetic domination of the mutation. The yeast transport plasmid-E. coli pRS315 (Sikorski RS et al., Genetics 122: 19-27, (1989)), which has genes CEN6, leu2, ampR, and is a low copy plasmid in yeast was used in the construction of the genomic library. In the over-expression experiment, the transport vector pRS425 (Christianson TW et al., Gene 110 (1): 119-22 (1992)), which has the genes leu2 and ampR, and is a high-cup plasmid, was used. in yeast. 40.3b Isolation of spontaneous resistant mutants The haploid S. cerevieiae strain ATCC201388 was grown overnight in YPD broth (BD, NJ USA) at 30 ° C and 1 mL of cells were plated on YPD agar plates (YPD + 1.5% broth). from Bacto-agar, BD, NJ USA) containing either 1.6, 3.2 or 6.4 μg / mL of CIO (equivalent to 4x, 8x, 16x MIC of CIO). The resistant mutants appeared after 2 days of incubation at 30 ° C. The frequency of resistance was determined by dividing the number of resistant mutants by the total number of cells in plaques as determined by dilutions in culture plate for 1 night on YPD plates. 40.3c Mutagéneeie EMS (ethyl methanesulfonate) At 2.5mL of the overnight culture, which was cultured in YPD medium, it was centrifuged at 700 X g for 5 minutes. The cell pellet was resuspended in 10 mL of pH buffer of 50 mM potassium phosphate, pH 7.0. The cell suspension was centrifuged again and the cell pellet was resuspended in phosphate buffer to obtain a cell density of 5 x 107 cells / mL as determined by counting the cells using a Petroff Hausser counting chamber.

(Horsham, PA E.U.A.). The cell suspension was shaken with 300 μL of EMS (Alfa Aesar, Ward Hill, MA, E.U.A.) for 30 minutes at 30 ° C. Mutagenesis was stopped by adding 10% (w / v) sodium thiosulfate (Sigma-Aldrich, St. Louis, MO, USA), and the cells were pelleted by centrifugation at 700 X g for 5 minutes and resuspended. in 1 mL of sterile H20. This was repeated one more time before the cells were plated on YPD agar plates containing 1.6 μg / mL of CIO. 40.3d Determination of MICe Minimum inhibitory concentration (MIC) was carried out essentially following the NCCLS guidelines highlighted in the M27 protocol with the exception of the use of YPS or synthetic defined medium (SDM). 40.3e Yeast pairing experiment The haploid mutants derived from S. cerevisiae ATCC201388 were mixed with S. cerevisiae ATCC 200901, and were incubated on YPD agar plates at 30 ° C for 4 hours. The cell mixture was inoculated on synthetic defined medium agar (BD, NJ E.U.A.) without the amino acids lysine and methionine, which are selective for diploids. 40.3f Construction of genomic DNA library of plaemidoe Genomic DNA was isolated from mutant strains using the DNeasy tissue kit from Qiagen (Valencia, CA, E.U.A.). Genomic DNA fragments of 4-10kb were generated by partial digestion with Mbo I from Fermantas (Hanover, MD, E.U.A.), followed by purification using Wizard®SV gel and PCR cleaning system (Promega, Madison Wl E.U.A.). The purified DNA fragments were ligated into pRS315 digested with BamH I (Fermantas, Hanover MD E.U.A.) using T4 DNA ligase (Fermantas, Hanover MD E.U.A.). The ligation mixture was dialyzed against water using the filters VSWP 0025 (Millipore, Billerica, MA, E.U.A.) before being electroporated into Escherichia coli E. cloni SUPREME cells (Lucigen, Middleton, Wl, E.U.A.) following the manufacturer's protocol. The transformants were plated on LB with 200 μg / ml carbinicillin and incubated overnight at 37 ° C. The transformants were combined and the plasmid DNA was isolated using Qiagen miniprep equipment (Valencia, CA, E.U.A.). The plasmid library was transformed into S. cerevisiae (Gietz, RD et al., Methods in Enzymology 305: 87-96 (2002)). 40. 3g Sequencing All sequencing was carried out by Sequetech Corporation (Mountain View, CA E.U.A.). 40.3g (l) Mutation mapping To further map mutations for specific domains in CDC60, the following three pairs of primers 5 'gcgaaaagaaacctaacgcatattc3' and 5 'ctatcgtgatccatacaagcttgac3', 5 'cgatagacaatccggtgaaggtgttac3' and 5 'catcccaaggcaatctggtacctaacc3' were used, and 'gaaaaatacttagttgagtctttatca3' and 'caccatgaggcatcttgaaatattctc3'. 40. 3h Cloning and eovere expreeeion of CDC60 type eilveetre in S. cerevieiae A DNA fragment BamH I-Sal I of 4. Okb containing the complete open reading frame CDC60 (ORF) and 700bp of upstream sequence was amplified using polymerase DNA KOD, genomic DNA S. cerevieiae (Novagen, Madison, Wl, USA), and the primers GAG GGA TCC GGT TAG TTT TAG TTC GCG AGT GAC CTG and GAG GTC GAC GAT TTC TGG TTG CTG TTT ATT GAT CTT (Operon, Alameda , CA, USA). This DNA fragment was then cloned into the multiple copy plasmid pRS425 2 uM, and transformed into S. cerevieiae ATCC201388 (Gietz, RD et al., Methods in Enzymology 305: 87-96 (2002)). 40.4 Results and Discussions 40. 4a Resistant mutant isolation From 5 x 109 cells, 600 spontaneous CÍO resistant mutants were isolated, which makes the resistance frequency 1.2 x 10 ~ 7 to 4 x MIC. Similar resistance frequencies were obtained for 8x and 16x MIC. EMS was also used to isolate CÍO resistant mutant. The use of EMS increased the mutagenic frequency 4,000 times. The MICs of 8 spontaneous mutants and 3 mutants generated by EMS were evaluated. All mutants showed an 8 to 64 fold improvement in resistance to CIO (Table 1). Table 1 MICs of CIO mutants induced by EMS and spontaneous 40. 4b CIO-resistant mutations that do not confer re-competition to another antimicotic To further characterize these resistant mutants, three CIO-resistant mutants were tested against several antifungal agents with known mechanisms of action. The mutants resistant to CÍO did not show any resistance to these compounds (Table 2), which suggests that CIO acts very different from these antifungal agents.

Table 2 CIO mutants not resistant to other antifungals 40. 4c Re-entitlement to CIO dominant To identify the gene that gives rise to resistance to CÍO, it was first determined whether the mutation was either dominant or recessive. The strain S. cerevi ei a e of origin and three mutants were selected and matched with S. cerevi ei ATCC 200901. The MIC of the diploids generated from the CÍO mutants was found to be 64 times larger than the diploids generated from the strain of origin (Table 3), suggesting that the mutations are dominant, and therefore, plasmid libraries were constructed from these three mutants resistant to haploid CÍO.

Table 3 CIO mutants are dominant 40. 4d The CDC60 gene confers resistance to CIO Plasmid libraries of the three mutants in S. cerevieiae ATCC201388 and selected in leucine agar minus SDM were transformed with 1 μg / mL of CIO. Plasmid DNA was isolated from the CIO-resistant transformants and electroporated into 10 G E. coli cells. The plasmid DNAs of the transformants resistant to E. coli carbenicillin were then transformed into S. cerevieiae ATCC201388 to confirm that the plasmids carried the gene for CIO resistance. A plasmid from each library that conferred resistance to CIO was sequenced and analyzed using a BLASTN search against the S. cerevieiae genome database (http: // seq.yeastgeno e.org / cgi-bin / nph-blast2sgd). The CDC60 gene was the only open reading frame identified in the cloned inserts of the two plasmids derived from the two plasmid libraries. Two genes, CDC60 and PET20, were revealed in the cloned insert of the remaining plasmid library. This suggests that these CIO-resistant mutations are located in the CDC60 gene, which codes for the cytoplasmic r-leucyl synthetase. CDC60 (leucyl tRNA synthetase) is one of 20 essential aminoacyl tRNA synthetases (ARS) that bind amino acids to the 2 'or 3' end of tRNAs. 40. 4e Mutations reeietentee CIO reeiden in the edit domain of CDC 60 The DNA sequence analysis of the plasmids derived from the three mutants showed that there was a single amino acid substitution in CDC60 of each of the three mutants (Table 4 ). Eight additional mutants were analyzed by amplifying CDC60 by colony PCR and transforming the resulting product into S. cerevisiae ATCC201388. All transformants were resistant to CIO and subsequent sequence analysis showed that all contained a single amino acid change within the CDC60 editing domain (Table 4). The function of ARS is to load the correct tRNA with the correct amino acid. In leucyl-tRNA synthetases the active site for the editing mechanism is located in a separate domain, which is polypeptide the connector polypeptide 1 (CP1), of the synthetic active site (Schmidt E. et al, Biochemistry 34 (35): 11204-10 (1995)). All amino acid substitutions of 11 mutants were located in this CPI domain, demonstrating a link between the function of editing the enzyme and the inhibitory activity of CIO. 40. 4f On expulsion of CDC60 type eilveetre in S. cerevieiae Since all 11 CIO-resistant mutants have simple amino acid substitutions in the leucyl-tRNA synthetase editing domain (Table 4), it is strongly suggested that CDC60 is the target for CIO If leucyl-tRNA synthetase is the target, increasing copies of CDC60 should increase resistance to CIO. To test this hypothesis, the wild type CDC60 gene was cloned into a multiple copy plasmid pRS425, and transformed into S. cerevieiae ATCC201388. As shown in Table 5, the MIC for this strain is eight times higher than for the same strain that carries PRS425. Table 4 Amino acid substitutions (AA) in CIO-resistant mutants Table 5 Expression of CDC60 increases resistance to CIO Example 41 Experiments for isolating mutant leucyl-tRNA transferase molecules that are also resistant to CÍO. The Saccharomycee cereviae wild type haploid strain ATCC 201388 (MATa his3? L leu2? 0 met5? 0 ura3? 0) was used for selection of clones showing resistance to CIO. Mutations in leucyl tRNA transferase were isolated in two forms. In a set of experiments, EMS was used as a chemical mutagenic agent. 2.5mL of a Culture 2x culture was washed with 50mM of potassium phosphate pH regulator, pH 7.0, and resuspended in 10 mL of the pH regulator to reach approximately 5x10 cells / mL. 300μL of EMS (Alfa Aesar, Ward Hill, MA) was added to the cells, which were then incubated for 30 min at 30 ° C with shaking. The mutagenesis process was stopped with the addition of 10% sodium thiosulfate (w / v) (Sigma-Aldrich, St. Louis, MO, E.U.A.). At the end of the mutagenesis cycle, the cells were washed 2x with water and then placed on YPD agar plates containing CIO.

In the second method, spontaneous mutant clones were isolated from the YPD plates containing CIO concentrations. The wild type haploid S. cerevieiae strain ATCC201388 (MATa his3? 1 leu2? 0 met5? 0 ura3? 0) were cultured overnight at YPD Difco broth (1% yeast extract, 2% Bacto Peptone, 2% glucose) at 30 ° C to reach l.OxlO8 cells / ml. The cells were concentrated by lOx in YPD broth, and 100 μL were plated on each of 30 YPD agar plates (YPD Difco ± 1.5% Bacto agar) containing 1.6, 3.2, 6.4 μg / mL of CIO (equivalent to 4x, 8x and 16x minimum inhibitory concentration of CIO). The. Resistant mutants appeared after 2 days of incubation at 30 ° C. The frequency of resistance is determined by the number of mutants and the total number of cells. '^ Minimum inhibitory concentration (MIC) evaluation was carried out using the NCCLS protocol. The yeast equalization experiment was carried out following the procedure in Methods in Enzymology by Guthrie, C etc. The genomic plasmid library for each clone was constructed using the yeast transport vector E. coli pRS315 and transformed into S. cerevisiae ATCC201388. Transformants were selected in synthetic defined medium with 0.2ug / mL leucine minus CIO. All the sequencing work was done by Sequeteq. Search was carried out ¿5 Blast using Saccharomyces genome database. Yeast transformation was carried out using LiAc / PEG method. Overexpression of CDC60 construction was made by using S. cerevisiae genomic DNA and two 5 'primers GAGGGATCCGGTTAGT TTTAGTTCGCGAGTGACC TG 3 A 5' GAGGTCGACGATTTCTGGTTGCT GTTTATTGATCTT 3 '. A total of 23 CIO-resistant mutants were isolated from S. cerevisiae. All mutants were dominant and had 8-64 fold improvement in CIO resistance on wild type in the evaluation of minimum inhibitory concentration. Further characterization of these mutants showed that they are not resistant to cross with any antifungal agents with known mechanisms of action. Determination of dominance / recessivity To identify the resistant gene in a mutant strain, it was first resolved if the mutation is dominant or recessive. The mutant was matched with a wild-type strain with opposite equalization type to make mutant diploid. There were two sets of genes in the resulting mutant diploid cells, one mutant resistant and the other wild type sensitive to CIO. If the diploid mutant was resistant to CIO, the mutated gene was dominant. To map the mutation, a plasmid library of the mutant strain was constructed and the library was transformed into the CIO-sensitive wild type strain to select for the resistant phenotype. If the mutant diploid was sensitive to CIO, the mutant gene could be identified as recessive. A12, F4, H4 were matched with a wild-type strain, respectively, as control; the strain of origin was also matched with the same strain. The minimal inhibitory concentrations of both wild type diploid and diploid mutants 3 are shown in Table 3. In comparison with wild type diploid, all 3 mutant diploids were resistant to CIO, indicating that the resistant mutation in these 3 mutants is dominant. Genetic mutation mapping All mutations in the 23 isolated CIO-resistant mutants were mapped to 11 residues in the CDC60 editing domain, the cytoplasmic leucyl-tRNA synthetase. To identify the mutation in the resistant mutant, 3 genomic libraries of mutant Al2, F4 and H4, respectively, were constructed. Plasmids with random genomic DNA fragment insert, size 4-40 kb, were retro-transformed into the wild-type strain of origin. Transformants with plasmids bearing resistant genes were selected on SDM-leu agar plates with addition of CIO. Then the plasmids were isolated and sent for sequencing. The nucleotide sequence of the insert was searched for BLAST against S. cerevisiae genome database and the results revealed that there was an individual ORF present in the insert of both plasmids isolated from the library of plasmids F4 and H4. This ORF was identified as CDC60, the cytoplasmic leucyl-tRNA synthetase, one of the 20 essential cytoplasmic inacylate tRNA synthetases in S. cerevieiae (there are 20 more in mitochondria). In addition to CDC60, there was a second petOR ORF present in the plasmid isolated from the A12 plasmid library, which codes for the protein required for respiratory growth and mitochondrial genome stability. To confirm that the CDC60 of these 3 mutants conferred resistance to CIO, the 3 plasmids were retro-transformed to wild-type strains of origin. Compared with the control transformation of the plasmid without CDC60, some with CDC60 of A12, F4, H4 gave > 1,000 more resistant colonies on YPD agar containing CIO, confirming that CDC60 of the 3 mutant strains contributed to CIO resistance. Sequence in CDC60 of each of the mutants containing individual amino acid etest. To identify if there is any amino acid substitution, the complete ORF of CDC60 of the resistant plasmids A12, F4 and H4 was sequenced. Comparing the non-wild type CDC60 sequence showed that there was an individual amino acid substitution in each of the 3 CDC60 (Table 4). In addition, sequence analysis of cDC60 from the rest of the 20 mutants showed that each contains an individual amino acid change within CDC60. DNA fragments containing each mutation were retro-transformed into wild-type strains. These transformations conferred resistance, indicating that the resistance of all mutants was due to the substitution of an individual amino acid in CDC60. CDC60 (leucyl-tRNA synthetase) is one of the tRNA-aminoacyl synthetases (ARS) that belong to the family of essential enzymes that bind amino acids to the 2 'or 3' end of the tRNAs, the charged tRNAs are then used in protein synthesis . Aminoacylation of tRNA is a two-step reaction: a) activation of amino acid with ATP by forming aminoacyl adenylates and b) transferring aminoacyl residue from aminoacyl adenylate to conga tRNA substrate. The accuracy of aminoacylation depends on both the specific recognition of amino acids during their activations (thick cut) and the pre- or post-transference edition (thin cut). Some of the ARS has included editing mechanism that specifically hydrolyzes structurally closed related deactivated amino acids. Leucyl-tRNA synthetase is one of those enzymes that can discriminate leucine from isoleucine and valine. The region that carries out this editing function is called connector polypeptide 1 (CP 1), it is a large insertion that interrupts the site of activity between the third and fourth strains b of the Rossman fold. All 11 amino acid substitutions of the 23 mutants were located in this CPl region, suggesting that there may be a link between the function of enzyme editing and CIO inhibition activity. Example 42 Assay to determine that CIO inhibits the editing domain of tRNA synthetase in a bacterium This example establishes a representative assay to determine whether a particular compound inhibits the editing domain of an ARS in a bacterium. The discharged [3H] -isoleucine ARNtleu was synthesized by incubating 1 μM of defective Cdc60p editing Saccharomycee cerevieiae (C326F) in 500 μL of 50mM Tris-HCl (pH 8.0), 60mM of MgCl2, 4mM of ATP, lmM of DTT, 0.02 % (w / v) of BSA, 4mg / mL of tRNA tRNA E. coli crude (Roche), 0. lmM isoleucine and 5 mCi L- [4,5- H] isoleucine (10OCi / mmoles, GE Healthcare) and 20% (v / v) DMSO for 1 hour at 30 ° C. The reaction was stopped by adding 10 μL of 10% acetic acid (v / v) followed by two extractions of phenol acid (Sigma). The tRNA discharged in the upper aqueous phase was removed and precipitated by adding two volumes of 96% (v / v) ethanol and incubated at -20 ° C for 30 minutes. The pellet was pelleted by centrifugation at 13,200 xg for 30 minutes and the pelleted tRNA pellet was washed twice with 70% (v / v) ethanol and then resuspended in 50 mM potassium phosphate buffer, pH 5.2 . The reaction was terminated after 2 hours of incubation at 30 ° C by the addition of acetic acid at 0.17% (v / v). The isoleucylated crude tRNALeu was purified by extracting twice with extractions of phenol acid-chloroform (pH 4.3), followed by ethanol precipitation. The tRNA pellet was washed twice with 70% ethanol, dried and then resuspended in 50 mM potassium phosphate (pH 5.0) and stored at -20 ° C. An aliquot was precipitated with 10% TCA (w / v) to quantify ile-RNAteu. Editing hydrolysis assays were carried out after transfer at 30 ° C in 50 mM Hepes (pH 8), 10 mM MgCl 2, 30 mM KCl, with crude 3 H-isoleucine-tRNA (-0.3 μCi / mL). Each reaction was initiated by the addition of the 150 nM enzyme. At each time point three aliquots of 20 μL of the reaction mixture were added to 200 μL of 10% TCA (w / v) in a Millipore filter plate and precipitated for 20 minutes at 4 ° C. The precipitate was filtered and washed three times with 200 μL of 5% TCA (w / v), then dried and 20 μL of scintillation super-mixture cotel added. Millipore filter plates were counted in the Trilux MicroBeta. The IC50 was determined by the amount of inhibitor that inhibited 50% activity, 100% editing after transfer was calculated by taking the non-enzymatic control activity of the wild-type enzyme activity. To compare the minimum inhibitory concentration (MIC) of a tolC strain Eecherichia coli carrying a pUC derived plasmid with and without a leuS gene insert. If the MIC of the strain carrying extra copies of leuS is 2 times larger than the control strain then pour LB agar plates not four times the concentration of the MIC of the compound. Plate 1 x 1010 E. coli in ten plates containing 4 x MIC of the compound. Incubate for 1-2 days at 37 ° C and collect ten colonies and deposit on 4 x MIC plates of LB agar to confirm resistance. Take a large colony of each of the ten mutants resistant to E. coli and resuspend them in 50 μL of pH-regulator PCR. Amplify the CDC60 editing domain using a PCR enzyme reading test and the following primers, ggcaccgtggacgtacgacaacatcgc and gggaaacaccccagtcgcgcaggcgg. Purify the PCR 980 bp product using either Qiagen or Promega PCR cleaning equipment. The sequence amplifies the mutant DNA and compares it with the wild type. If the mutant DNA carries mutations in the editing domain the inhibitor affects leucyl-tRNA synthetase by the editing domain. Example 43 Assay to determine which Assay during determining 'that CIO inhibits the editing domain of tRNA synthetase in a fungus This example details an exemplary assay to determine whether a selected compound inhibits the editing domain of an ARS in a fungus. The discharged [3H] -isoleucine RNAtleu was synthesized by incubating 1 μM of defective Cdc60p Saccharomycee editing cerevieiae (C326F) in 500 μL of 50mM Tris-HCl (pH 8.0), 60mM of MgCl2, 4mM of ATP, lmM of DTT, 0.02% (w / v) of BSA, 16 μM of tRNA of brewer's yeast (Roche ), O.lmM of isoleucine and 5 mCi L- [4, 5-3H] isoleucine (10OCi / mmoles, GE Healthcare) and 20% (v / v) DMSO for 1 hour at 30 ° C. The reaction 0 was stopped by adding 10 μL of 10% acetic acid (v / v) followed by two extractions of phenol acid (Sigma). The tRNA discharged in the upper aqueous phase was removed and precipitated by adding two volumes of 96% (v / v) ethanol and incubated at -20 ° C for 30 minutes. The precipitate was granulated by centrifugation at 13,200 xg for 30 minutes and the discharged tRNA pellet was washed twice with 70% (v / v) ethanol and then resuspended in 50 mM of pH potassium phosphate buffer, pH 5.2. The reaction was finished after 2 hours of 2 ^ incubation at 30 ° C by the addition of acetic acid at 0.17% (v / v). The isoleucylated crude tRNALeu was purified by extracting twice with extractions of phenol acid-chloroform (pH 4.3), followed by ethanol precipitation. The tRNA pellet was washed twice with 70% ethanol, dried and then returned to ¿> suspend in 50 mM potassium phosphate (pH 5.0) and store at -20 ° C. An aliquot was precipitated with 10% TCA (w / v) to quantify ile-tRNALeu. Editing hydrolysis assays were carried out after transfer at 25 ° C in 50 mM Hepes (pH 7.5), 10 mM MgCl2, 30 mM KCl, with crude 3 H-isoleucine-tRNA (-0.3 μCi / mL). Each reaction was initiated by the addition of the 150 nM enzyme. At each time point three aliquots of 20 μL of the reaction mixture were added to 200 μL of 10% TCA (w / v) in a Millipore filter plate and precipitated for 20 minutes at 4 ° C. The precipitate was filtered and washed three times with 200 μL of 5% TCA (w / v), then dried and 20 μL of scintillation super-mixture cotel added. Millipore filter plates were counted in the Trilux MicroBeta. The IC50 was determined by the amount of inhibitor that inhibited 50% activity, 100% editing after transfer was calculated by taking the activity of the non-enzymatic control of the editing activity after transfer of wild-type enzyme. EXAMPLE 44 Equilibrium dialysis Equilibrium dialysis experiments were carried out on the pH regulator AARS containing 50 mM Hepes-KOH (pH 8.0), 30 mM MgCl2 and 30 mM KCl. The experiments were carried out using 5k MWCO DispoEquilibrium Dialyzer apparatus (Harvard Apparatus, Holliston, MA).

On one side of the dialysis membrane (side A), [methylene-14C] CIO, 2.04 GBq / mmole (Amersham) was added at concentrations ranging from 1 to 200 uM in 20 μL. On the opposite side of the membrane (B side), 30 uM of recombinant CdcdOp (Saccharomycee cerevisiae cytoplasmic LeuRS) and 10 mM of AMP (5'-monophosphate adenosine, Sigma) was added in 20 μL. The samples were incubated at room temperature (21 ° C) while being shaken for 4.5 hours to establish IOC equilibrium across the membrane. At equilibrium, CIO on each side of the dialysis membrane was quantified by scintillation counting using a Wallac MicroBeta Trilux Model 1450 liquid scintillation counter. The amount of CIO bound to Cdc60p was determined by subtracting [C10] A from [C10] B. PPi exchange assay The PPi exchange assay was carried out on the pH regulator AARS containing 50 mM Hepes-KOH (pH 8.0), 30 mM MgCl2 and 30 mM KCl supplemented with 2 mM ATP and [32P ] PPi (105 cpm / μmoles), 2 mM of leucine and 7 nM of recombinant Cdc60p. Experiments were carried out in the presence or absence of CIO (15 μM) and tRNA (16 μM). After an incubation of 20 minutes at 30 ° C, the reactions were initiated by the addition of ATP. At various time intervals, 45 μL of reaction mixture was added to 100 μL of 2% perchloric acid and 0.1 M Na4P207 to rapidly quench the reaction. Then radioactive ATP It was absorbed for activated carbon by the adicoin of 30 μL of a suspension of Norit A washed with acid. This mixture was filtered through GF / C glass filters and washed 2x with 200 μL of distilled water then lx with 200 μL of 95% ethanol. The filters were dried and counted scintillation using a Wallac MicroBeta Trilux Model 1450 liquid scintillation counter. Synthesis of triTiada excreted tNTLeu The RNAlet discharged from I3H] -isoleucine was synthesized by incubating 1 μM of defective Cdc60p editing of Saccharomyces cerevieiae (C326F ) in 500 μL of 50mM Tris-HCl (pH 8.0), 60mM MgCl2, 4mM ATP, lmM DTT, 0.02% (w / v) BSA, 16 μM tRNA of brewer's yeast (Roche), O.lmM of isoleucine and 5 mCi of L- [4, 5 -3H] isoleucine (10OCi / mmoles, GE Healthcare) and 20% (v / v) DMSO for 1 hour at 30 ° C. The reaction was stopped by adding 10 μL of 10% (v / v) acetic acid followed by two extractions of phenol acid (Sigma). The tRNA discharged in the upper aqueous phase was removed and precipitated by adding two volumes of 96% (v / v) ethanol and incubated at -20 ° C for 30 minutes. The pellet was pelleted by centrifugation at 13,200 xg for 30 minutes and the pelleted tRNA pellet was washed twice with 70% (v / v) ethanol and then resuspended in 50 mM potassium phosphate buffer, pH 5.2 . Post-transfer editing assay The [3H] -isoleucine, 40nM, unloaded steroleu substrate was added to 50mM Hepes-KOH pH 8.0, 30mM KCl, 30mM MgCl2, 0.02% (w / v) BSA, lmM DTT, 2.4 nM of CdcdOp S. cerevisiae at 30 ° C to initiate the reaction and 20 μL of aliquots, taken at set time points, were added to ice cold 200 μL of 10% trichloroacetic acid (w / v) cooled on ice (TCA). The TCA precipitates were washed twice with 200 μl of 5% TCA cooled in ice (w / v) and filtered through a multi-screen HA HTS filter (Millipore). Optiphase scintillation cocktail (Perkin Elmer) filters were added and the TCA precipitate was counted in a Wallac MicroBeta Trilux Model 1450 liquid scintillation counter. Example 45 Assay to determine which compounds inhibit synthesis activity Aminoacylation assays were carried out to determine the net velocity of synthesis leucine / tRNALeu by leucyl-tRNA synthetase. Experiments were carried out in 500 μL reaction mixtures containing 1 x pH regulator AARS (50 mM Hepes-KOH (pH 8.0), 30 mM MgCl2 and 30 mM KCl) supplemented with 20 uM [14C] -leucine (Perkin-Elmer, 11.32 GBq / mmole.), 16 uM of crude yeast tRNA, 0.02% of BSA, 1 mM of dithiothreitol, 2 nM of LeuRS of recombinant yeast (CDC60) and 2 mM of ATP. The reactions were carried out at 30 ° C. At time zero, reactions were initiated by the addition of ATP. At various time intervals, 20 ul aliquots were added to 150 ul of 10% trichloroacetic acid (TCA) within an individual well of a 96-well nitrocellulose membrane filter plate (Millipore Multiscreen HTS, MSHAN4B50). Each well was then washed 3x with 100 ul of 5% TCA. The filter plates were then dried under heating lamp and the precipitated [14 C] -leucine / tNtLeu complexes were quantified by liquid scintillation counting using a Wallac MicroBeta Trilux Model 1450 liquid scintillation counter. The inhibitory effects of compounds containing boron, was determined by the addition of up to 100 uM of the compound in the reaction mixture for 20 minutes before the addition of ATP. Example 46 Test article and dose formulation CIO (5-fluoro-l, 3-dihydro-1-hydroxy-2, 1-benzoxazole), 5-fluoro-l, 3-dihydro-1-phenyl-2, were obtained. 1-benzoxazole, Cl (5-chloro-l, 3-dihydro-l-hydroxy-2, 1-benzoxazole) and 5-fluoro-l, 3-dihydro-1- (3-hydroxymethylphenyl) -2, 1-benzoxazole of Anacor Pharmaceuticals, Inc. (Palo Alto, CA). [1C] -C10 was synthesized by Amersham Biosciences UK Limited (Buckinghamshire HP &9NA, UK) radiochemical purity and > 99.3% and 55 mCi / mmoles, respectively. 91 Penlac ™ nail varnish (topical solution with 8% ciclopirox) was manufactured by Dermik (Ber yn, PA). [1 C] -Cyclopirox (pyridinone-6- (14C) -cyclopirox) was synthesized by PerkinElmer Life and Analytical Sciences (Boston, MA). The radiochemical purity and specific activity of the chemical was > 95% and 12.5 mCi / mmoles, respectively. Experiment 1: Sieving of four oxaborol compounds CIO, 5-fluoro-l, 3-dihydro-l-phenyl-2, 1-benzoxazole, Cl, and 5-fluoro-l, 3-dihydro-1- (3-hydroxymethylphenyl) -2, 1-benzoxazole, formulated at 10% w / v in ethanol, were evaluated. An individual aliquot (100) of each formulation was dosed to the top of the human nail plates using the nail penetration procedure described below, and allowed to stand for 3 days. The dosed area was washed, and then the cotton ball bed supporting the nail and the nail samples were collected at the end of the incubation period, stored at 4 ° C and analyzed for drug using LC / MS / MS. Experiment 2: Carrier effect on CIO nail penetration The following formulations were evaluated, all containing 10% CIO. Formulation A: 70% ethanol, 20% poly (vinyl methyl ether monobutyl maleic acid ester (v / v); Formulation B: 6% ethanol, 14% water, 15% methacrylate poly (2) -hydroxyethyl), 5% dibutyl sebacate (v / v), Formulation C: 55% ethanol, 15% ethyl acetate, 15% poly (vinyl acetate), 5% dibutyl sebacate (v / v); Formulation D: 20% propylene glycol, 70% ethanol (v / v) Using the nail penetration procedure described below, aliquots (10 μL) of the dose formulations were applied to human nail plates once per day for 14 days with a daily wash before dosing.The cotton ball bed that supports the nail was collected from each cell chamber and replaced with a new one on day 5, 10 and 15 after the first dose. Nail samples were collected at the end of the dose period on day 14, stored at 4 ° C and analyzed for drug by LC / MS / MS Experiment 3: Penetration of CÍO after 14-day multiple-dose treatment Two test items, CÍO, 10% in propylene glycol and ethanol (1: 4, v / v) and ciclopirox, 8% in Penlac ™ nail varnish were compared for their speed of penetration into and through the human nail plate. Small amounts of carbon-radiolabelled CÍO 14 and ciclopirox were added to their respective formulations the day before the first dose. Using the nail penetration procedure described below, aliquots (10 μL) of the dose formulations were applied to human nail plates once a day for 14 days with a wash before each dose. The cotton ball bed supporting the nail was collected from each cell chamber and replaced with a new one every 72 hours after the pyremera dose (days 3, 6, 9, 12, and 15). The nail samples were collected at the end of the dose period on day 14. The radioactivity of all the samples was analyzed and compared. Nail Penetration Procedure Details of the 9 '10 nail incubation have been previously described. Briefly, a healthy fingernail plate was mounted in a chamber diffusion cell (Figure 1, Permegear, Inc., Hellerto n, PA) with the nail surface (upper center) open to air and the inner surface in contact with a small cotton ball that acts as a support nail bed. The cotton ball of support under the nail was moistened by normal saline that provided moisture to the nail plate, and the degree of hydration was monitored and controlled during the experiment. The incubation period started 24 hours before the first dose, and ended 24 hours after the final dose. Aliquots were applied (10 μL) to the surface of the nail plate once daily. Washing of dosed surface area was carried out at the end of the incubation period (druatne single dose study), or every morning before starting dosing on the second day (multiple dose study). The dosed surface area of the nail was washed with cotton swabs in a cycle as follows: twice with ethanol, then with 50% Ivory® liquid soap (Procter &Gamble, Cincinnati, Ohio), then twice with water distilled The wash samples from each cycle were combined and the radioactivity was measured. After finishing the dosage and the incubation phase, the nail plate was transferred to a cutting carrier for sampling. Under controlled humidity and temperature, no abnormal situation was observed such as change in nail plate color, hydration changes, or fungal growth during the 14-day dosing period. The nail plate was secured in position so that the external dorsal dosed surface was facing the wearer. The cutting carrier moved to bring the plate surface just in contact with the tip of the cutter. The drill was then started and a fine adjustment moved the platform towards the cutter tip, removing a powder sample from the nail. In this way, an orifice of approximately 0.3-0.4 mm in depth and 7.9 mm in diameter is drilled in each nail, enabling the collection of dust sample from the center of each ventral surface of the nail. These samples are referred to as samples taken from the "ventral / intermediate nail plate center". Then the nail outside the dose area (and also the sampling area) was cut and saved as the "remaining nail plate". The layer above the powder sampling area was also saved as "the dorsal / intermediate center". All the nail plate samples were collected individually in a glass scintillation vessel and weighed. Quantitative analysis of oxaboroles LC / MS / MS (API3000, Applied Biosystems, Foster City, CA) was used to quantify the amounts of non-radiolabeled oxaboroles, CIO, 5-fluoro-l, 3-dihydro-l-phenyl-2, 1 -benzoxazole, Cl, and 5-fluoro-1,3-dihydro-l- (3-hydroxymethylphenyl) -2, 1-benzoxazole in samples of nail penetration studies. For the cotton ball analysis, eleven calibration standards were prepared in normal saline solution. A volume of 100 μL of standard cacda was added in a fresh cotton ball with calibration standard concentrations of 0, 2.5, 5, 10, 20, 40, 80, 160, 320, 640, 1280, and 2560 μg / mL. Acetonitrile (Burdick &Jackson, Muskegon, MI) containing the internal standard p-nitrophenol (PNP) was added to all cotton balls. Samples of cotton balls and any residual solvents were transferred to centrifuge filter tubes. After centrifugation, the filtrate from the cotton ball samples was transferred to autosampled containers and analyzed by LC / MS / MS. For cyclopirox samples, the filtrate was first derived with dimethyl sulfate according to a method previously described before analysis by LC / MS / MS (Myoung and Choi, 2003). Samples with concentrations calculated above the highest calibration standard were diluted 10- or 20-fold with acetonitrile containing the internal standard p-nitrophenol (TCI America, Portland, OR). For nail analysis, two separate calibration curves were prepared, one for nail powder analysis and the other for top nail analysis. Each curve contained eleven calibration standards. The standards for dimethyl sulfoxide were first prepared. A volume of 10 μL of each standard was added in keratin powder (6.5 mg for nail powder curve and 17 mg for top of the nail curve). Nail samples were digested with NaOh IN overnight at 45 ° C. The next morning, before extraction with methylene chloride, the pH of the samples was adjusted to pH 3. After extraction, the organic layer was transferred and evaporated. The samples were reconstituted in acetonitrile and analyzed by LC / MS / MS using a 5 μm, 2.1 x 50 mm Eclipse XDB-C18 column (Agilent, Wilmington, DE) and a gradient mobile phase of 5 mM ammonium acetate and acetonitrile. Measurement of radioactivity All measurements of radioactivity were carried out with a liquid scintillation counter Model 1500 (Packard Instrument Company, Downer Grove, IL). The counter was audited for accuracy using sealed samples of rapidly cooled standards and not quenched rapidly as detailed for the instrument manual. The counting efficiency 1C is equal to or greater than 95%. All nail samples were pre-treated with packard soluene-350 were incubated at 40 ° C for 48 hours followed by the addition of 10 mL of scintillation cocktail (HIONIC-FLUOR, Packard Instrument Company, Meriden, CT). Other samples (standard dose, surface wash and bed material) were mixed directly with Universal ES scintillation cocktail (ICN Biomedicals, Costa Mesa, CA). Test samples and background checks were counted for 3 minutes each for radioactivity. Calculations and data analysis The quantification of non-radioactive compounds was based on peak area ratios of the compound to the internal standard. The regression method for the calibration curves was selected based on the best fit. A linear and quadratic regression with 1 / x or 1 / x weighted square was used. All integrations were carried out using Analyst version 1.3 (Applied Biosystems Foster City, CA). The concentrations of the compound in the cotton balls were converted to absolute quantities by taking the sample volume of 100 μL into account. The amount of compound in the nail powder and top of the nail were adjusted for their respective weights and reported in μg / mg. The average and individual amount (± S.E.) of the test chemical equivalent in the nail, delegate material and wash samples are presented as dpm, μCi, percent applied dose and mg equivalent at each time point. The concentration of labeled 14C test chemicals was calculated from the value based on specific activity of each labeled test chemical [14C]. The concentration information of test chemical not labeled in the topical formulation was obtained from the manufacturers. The total concentration of test chemical equivalent is the sum of the concentration of test chemical labeled 14C and the concentration of unlabeled test chemical. The value of the total amount of the test chemical equivalent in each nail sample was calculated from those values based on radioactivity of the sample and the ratio of test chemical equivalent total mg and radioactivity of the test chemical. The data was normalized further by dividing them with the weight of the sample. The level of significance of nail samples from each two groups was analyzed by student t-test. It is understood that the examples and embodiments herein are for purposes of illustration only and that various modifications or changes in view thereof will be suggested to persons skilled in the art and are to be included within the spirit and scope of this application and scope. of the appended claims. All publications, patents and patent applications cited herein are incorporated herein by reference in their entirety for all purposes. It is noted that in relation to this date, the best method known to the applicant to carry out the aforementioned invention, is that which is clear from the present description of the invention.

Claims (192)

1. CLAIMS Having described the invention as above, the content of the following claims is claimed as property: 1. A compound characterized in that it has a structure according to the following formula: R1 and R2 are members independently selected from H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl; wherein R1 and R2, together with the atoms to which they are attached, can optionally be joined to form a 4 to 7 membered ring; zl is a selected member of wherein R3a and R4a are members independently selected from H, cyano, substituted or unsubstituted alkyl, heteroalkyl substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl; R5 is a member selected from halogen and OR8. wherein R8 is a member selected from H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl. A is a selected member of CR9a and N. D is a selected member of CR10a and N. E is a selected member of CRlla and N. G is a selected member of CR12a and N. where R9a, Rlla and R12a are selected members independently of H, OR *, NR * R **, SR *, -S (0) R *, -S (0) 2R *, -S (0) 2NR * R **, nitro, halogen, cyano, alkyl substituted or unsubstituted, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl. wherein each R * and R ** are members independently selected from H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl replaced. wherein R9a and R10a together with the atoms to which they are attached, optionally join to form a ring. wherein R10a and Rlla, together with the atoms to which they are attached, optionally join to form a ring. wherein Rlla and R12, together with the atoms to which they are attached, optionally join to form a ring. The combination of nitrogens (A + D + E + G) is an integer selected from 0 to 3 with the proviso that the compound is not a member selected from: 2. The compound according to claim 1, characterized in that the compound has the structure according to the formula (IX) 3. The compound according to claim 1, characterized in that the R1 and R2 are each independently selected from H, substituted or unsubstituted methyl, substituted or unsubstituted ethyl, substituted or unsubstituted propyl, substituted or unsubstituted isopropyl, substituted butyl or unsubstituted or substituted or unsubstituted t-butyl, substituted or unsubstituted phenyl and unsubstituted or substituted benzyl, and wherein R1 and R2, together with the atoms to which they are attached, may optionally be joined to form a member selected from substituted or unsubstituted dioxaborolane, substituted or unsubstituted dioxaborin, and substituted or unsubstituted dioxaborepane. 4. The compound in accordance with the claim 3, characterized in that R1 and R2, together with the atoms to which they are attached, can form a member selected from substituted or unsubstituted dioxaborolane, substituted or unsubstituted tetramethyldioxaborolane, substituted or unsubstituted phenyldioxaborolane, dioxaborin, dimethyldioxaborin, and dioxaborepane. 5. The compound according to claim 1, characterized in that Zl a member selected from and R 5 is a member selected from substituted or unsubstituted methoxy, substituted or unsubstituted ethoxy, substituted or unsubstituted methoxymethoxy, substituted or unsubstituted ethoxyethoxy and unsubstituted or substituted tetrahydro-2H-pyran-2-yloxy. 6. The compound according to claim 1, characterized in that R3a is H and R4a is a member selected from methyl, ethyl, propyl, butyl, phenyl, benzyl and cyano. The compound according to claim 1, characterized in that R9a, R10a, Rlla and R12a are members independently selected from H, halogen, cyano, nitro, substituted or unsubstituted methoxy, substituted or unsubstituted methyl, substituted or unsubstituted ethoxy substituted ethyl or unsubstituted, trifluoromethyl, substituted hydroxymethyl or unsubstituted, substituted hydroxyalkyl or unsubstituted, substituted or unsubstituted benzyl, substituted or unsubstituted phenyl, phenyloxy substituted or unsubstituted, phenylmethoxy substituted or unsubstituted, tiofeniloxi substituted or unsubstituted I pyridinyloxy substituted or unsubstituted, substituted pyrimidinyloxy or unsubstituted, substituted or unsubstituted bencilfurano, substituted or unsubstituted methylthio, I mercaptobencilo substituted or unsubstituted, mercaptoalkyl substituted or unsubstituted, substituted or unsubstituted phenylthio, substituted tiofeniltio or unsubstituted phenylmethylthio substituted or unsubstituted, substituted pyridinylthio or unsubstituted, substituted pyrimidinylthio or unsubstituted, substituted benciltiofuranilo or unsubstituted, substituted phenylsulfonyl or unsubstituted, substituted benzylsulfonyl or unsubstituted, substituted phenylmethyl or unsubstituted tiofenilsulfonilo substituted or unsubstituted pyridinylsulfonyl substituted or unsubstituted, pirimidinilsulfonilo substituted or unsubstituted , sulfonamidyl substituted or unsubstituted, substituted or unsubstituted phenylsulfinyl, substituted or unsubstituted benzylsulfinyl, substituted fenilmetilsulfinilo or unsubstituted tiofenilsulfinilo substituted or unsubstituted, pirimidinilsulfinilo substituted or unsubstituted, substituted or unsubstituted amino, alkylamino substituted or unsubstituted dialkylamino substituted or unsubstituted, substituted or unsubstituted trifluoromethylamino, substituted or unsubstituted aminomethyl, substituted or unsubstituted alkylaminomethyl, substituted or unsubstituted dialkylaminomethyl, substituted or unsubstituted arylaminomethyl, ben substituted cilamino or unsubstituted phenylamino substituted or unsubstituted, tiofenilamino substituted or unsubstituted, substituted pyridinylamino or unsubstituted, substituted pyrimidinylamino or unsubstituted indolyl substituted or unsubstituted morpholino substituted or unsubstituted alkylamido substituted or unsubstituted arylamido substituted or unsubstituted, substituted or unsubstituted ureido, substituted or unsubstituted carbamoyl and substituted or unsubstituted piperizinyl. The compound according to claim 1, characterized in that R9a, R10a, Rlla and R12a are members independently selected from H, fluoro, chloro, bromo, nitro, cyano, amino, methyl, hydroxylmethyl, trifluoromethyl, methoxy, trifluoromethoxy, ethyl , diethylcarbamoyl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, pyrimidinyl, piperazino, piperizinyl, piperizinocarbonilo, piperizinilcarbonilo, carboxyl, 1-tetrazolyl, 1-ethoxycarbonylmethoxy, carboxymethoxy, thiophenyl, 3- (butylcarbonyl) phenylmethoxy, 1H-tetrazol-5-yl, 1-ethoxycarbonylmethyloxy-, 1-ethoxycarbonylmethyl-, 1-ethoxycarbonyl-, carboxymethoxy-, thiophen-2-yl, thiophen-2-ylthio-, thiophen-3-yl, thiophen-3 -thio, 4-fluorophenylthio, butylcarbonylphenylmethoxy, butylcarbonylphenylmethyl, butylcarbonylmethyl, 1- (piperidin-1-yl) carbonyl) methyl, 1- (piperidin-1-yl) carbonyl) methoxy, 1- (piperidin-2-yl) carbonyl) methoxy, 1- (piperidin-3-yl) carbonyl) methoxy, 1- (4- (pyrimidin-2-yl) piperazin-1-yl) carbonyl) methoxy, 1- (4- (pyrimid in-2-yl) piperazin-1-yl) carbonyl) methyl, 1- (4- (pyrimidin-2-yl) piperazin-1-yl) carbonyl, 1-4- (pyrimidin-2-yl) piperazin-1 -ilo, l- (4- (pyridin-2-yl) piperazin-1-yl) carbonyl), 1- (4- (pyridin-2-yl) piperazin-1-yl) carbonylmethyl, (1- (4- (pyridine -2-yl) piperazin-1-yl) carbonyl) -methoxy), l- (4- (pyridin-2-yl) piperazin-1-yl, lH-indol-1-yl, morpholino-, morpholinyl, morpholinocarbonyl, morpholinylcarbonyl, phenylureido, phenylcarbamoyl, acetamide, 3- (phenylthio) -1H-indol-1-yl, 3- (2-cyanoethylthio) -lH-indol-1-yl, benzylamino, 5-methoxy-3- (phenylthio) - lH-indol-1-yl, 5-methoxy-3- (2-cyanoethylthio) -lH-indol-1-yl)), 5-chloro-lH-indol-l-yl, 5-chloro-3- (2 -cyanoethylthio) -lH-indol-1-yl)), dibenzylamino, benzylamino, 5-chloro-3- (phenylthio) -lH-indol-1-yl), 4- (lH-tetrazol-5-yl) phenoxy 4- (lH-tetrazol-5-yl) phenyl, 4- (lH-tetrazol-5-yl) phenylthio, 2-cyanophenoxy, 3-cyanophenoxy, 4-cyanophenoxy, 2-cyanophenylthio, 3-cyanophenylthio, 4-cyanophenylthio , 2-chlorophenoxy, 3-chlorophenoxy, 4-chlorophenoxy, 2-fluorophenoxy, 3-fluorophenoxy, 4-fluorophenoxy, 2-cyanobenzyloxy, 3-cyanobenzyloxy, 4-cyanobenzyloxy, 2-chlorobenzyloxy, 3-chlorobenzyloxy i, 4-chlorobenzyloxy, 2-fluorobenzyloxy, 3-fluorobenzyloxy and 4-fluorobenzyloxy. 9. The compound according to claim 8, characterized in that R9a is H and R12a is H. 10. The compound according to claim 9, characterized in that the compound is a member selected from 11. The compound according to claim 10, characterized in that the compound is a member selected from 25 25 12. A compound characterized in that it has the structure according to the following formula: wherein R1 and R2 are members independently selected from H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl; wherein R1 and R2, together with the atoms to which they are attached, can optionally be attached to form a ring. R3a and Ra are members independently selected from H, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl; and X is a member selected from bromine, iodine, triflate and diazo; A is a selected member of CR9a and N; D is a member selected from CR10a and N; E is a selected member of CRlla and N; G is a member selected from CR12a and N; wherein R9a, R10a, Rlla and R12a are members independently selected from H, OR *, NR * R **, SR *, -S (0) R *, -S (0) 2R *, -S (0) 2NR * R **, -C (0) R *, -C (0) OR *, -C (0) NR * R **, nitro, halogen, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, unsubstituted or substituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl; wherein each R * and R ** is a member independently selected from H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted heteroaryl or not replaced; wherein R10a and Rlla, together with the atoms to which they are attached, optionally join to form a ring; wherein R10a and Rlla, together with the atoms to which they are attached, optionally join to form a ring; where Rlla and R12a, together with the atoms to which they are attached, optionally join to form a nitrogenous combination (A + D + E + G) is an integer selected from 0 to 3. 13. The compound in accordance with claim 12, characterized in that the compound has the structure according to the formula (Xa): 14. The compound according to claim 12, characterized in that R1 and R2 are each members independently selected from H, methyl, ethyl, propyl, isopropyl, butyl, t-butyl, phenyl and benzyl, and wherein R1 and R2, together with the atoms to which they are attached form a selected member of substituted or unsubstituted dioxaborolane, substituted or unsubstituted dioxaborin, and substituted or unsubstituted dioxaborepane. 15. The compound according to claim 12, characterized in that X is a member selected from iodine and bromine. 16. The compound according to claim 12, characterized in that R3a and R4a are each members independently selected from H, methyl, ethyl, propyl, butyl, phenyl, benzyl and cyano. The compound according to claim 12, characterized in that R9a, R10a, Rlla and R12a are members independently selected from H, halogen, cyano, nitro, substituted or unsubstituted methoxy, substituted or unsubstituted methyl, substituted or unsubstituted ethoxy , substituted or unsubstituted ethyl, trifluoromethyl, substituted or unsubstituted hydroxymethyl, substituted or unsubstituted hydroxyalkyl, substituted or unsubstituted benzyl, substituted or unsubstituted phenyl, substituted or unsubstituted phenyloxy, substituted or unsubstituted phenylmethoxy, Tiofeniloxi substituted or unsubstituted, substituted pyridinyloxy or unsubstituted, substituted pyrimidinyloxy or unsubstituted, substituted bencilfurano or unsubstituted, substituted methylthio or unsubstituted, mercaptobencilo substituted or unsubstituted, mercaptoalkyl substituted or unsubstituted, substituted phenylthio or unsubstituted tiofeniltio substituted or unsubstituted, substituted phenylmethylthio or unsubstituted, substituted pyridinylthio or unsubstituted, substituted pyrimidinylthio or unsubstituted, substituted benciltiofuranilo or unsubstituted, substituted phenylsulfonyl or unsubstituted, substituted benzylsulfonyl or unsubstituted, substituted phenylmethyl or unsubstituted tiofenilsulfonilo substituted or unsubstituted, substituted or unsubstituted pyridinylsulfonyl, substituted or unsubstituted pyrimidinylsulfonyl, substituted or unsubstituted sulfonamidyl, unsubstituted or substituted phenylsulfinyl, substituted or unsubstituted benzylsulfinyl, unsubstituted or substituted phenylmethylsulfinyl, thiofe nilsulfinilo substituted or unsubstituted, pirimidinilsulfinilo substituted or unsubstituted, substituted or unsubstituted amino, alkylamino substituted or unsubstituted, substituted or unsubstituted dialkylamino, unsubstituted trifluoromethylamino substituted or unsubstituted aminomethyl substituted or unsubstituted alkylaminomethyl substituted or unsubstituted dialkylaminomethyl substituted or unsubstituted, arilaminometilo substituted or unsubstituted, substituted benzylamino or unsubstituted, substituted phenylamino or unsubstituted tiofenilamino substituted or unsubstituted, substituted pyridinylamino or unsubstituted, substituted pyrimidinylamino or unsubstituted indolyl substituted or unsubstituted, substituted morpholino or substituted, substituted or unsubstituted alkylamido, substituted or unsubstituted arylamido, substituted or unsubstituted ureido, substituted or unsubstituted carbamoyl and substituted or unsubstituted piperizinyl. 18. The compound according to claim 12, characterized in that R9a, R10a, Rlla and R12a are members independently selected from H, fluoro, chloro, bromo, nitro, cyano, amino, methyl, hydroxylmethyl, trifluoromethyl, methoxy, trifluoromethoxy, ethyl. , diethylcarbamoyl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, pyrimidinyl, piperazino, piperizinyl, piperizinocarbonilo, piperizinilcarbonilo, carboxyl, 1-tetrazolyl, 1-ethoxycarbonylmethoxy, carboxymethoxy, thiophenyl, 3- (butylcarbonyl) phenylmethoxy, lH-tetrazol-5-yl, 1-ethoxycarbonylmethyloxy-, 1-ethoxycarbonylmethyl-, 1-ethoxycarbonyl-, carboxymethoxy-, thiophen-2-yl, thiophen-2-ylthio-, thiophen-3-yl, thiophen-3 -thio, 4-fluorophenylthio, butylcarbonylphenylmethoxy, butylcarbonylphenylmethyl, butylcarbonylmethyl, 1- (piperidin-1-yl) carbonyl) methyl, 1- (piperidin-1-yl) carbonyl) methoxy, 1- (piperidin-2-yl) carbonyl) methoxy, 1- (piperidin-3-yl) carbonyl) methoxy, 1- (4- (pyrimidin-2-yl) piperazin-1-yl) carbonyl) methoxy, 1- (4- (pyrimidine -2-yl) piperazin-1-yl) carbonyl) methyl, 1- (4- (pyrimidin-2-yl) piperazin-1-yl) carbonyl, 1-4- (pyrimidin-2-yl) piperazin-1- ilo, 1- (4- (pyridin-2-yl) piperazin-1-yl) carbonyl), 1- (4 -. (pyridin-2-yl) piperazin-1-yl) carbonylmethyl, (1- (4- (pyridin-2-yl) piperazin-1-yl) carbonyl) -methoxy), 1- (4- (pyridin-2-yl) piperazin-1-yl, 1 H -indol-1-yl, morpholino-, morpholinyl, morpholinocarbonyl, morpholinylcarbonyl, phenylureido, phenylcarbamoyl, acetamide, 3- (phenylthio) -lH-indol-1-yl, 3- (2-cyanoethylthio) -lH-indol-1-yl, benzylamino, 5-methoxy-3- (phenyl) ) -lH-indol-1-yl, 5-methoxy-3- (2-cyanoethylthio) -lH-indol-1-yl)), 5-chloro-lH-indol-1-yl, 5-chloro-3- (2-cyanoethylthio) -lH-indol-1-yl)), dibenzylamino, benzylamino, 5-chloro-3- (phenylthio) -lH-indol-1-yl), 4- (lH-tetrazol-5-yl) ) phenoxy, 4- (lH-tetrazol-5-yl) phenyl, 4- (lH-tetrazol-5-yl) phenylthio, 2-cyanophenoxy, 3-cyanophenoxy, 4-cyanophenoxy, 2-cyanophenylthio, 3-cyanophenylthio, 4 -cyanophenylthio, 2-chlorophenoxy, 3-chlorophenoxy, 4-chlorophenoxy, 2- fluorophenoxy, 3-fluorophenoxy, 4-fluorophenoxy, 2-cyanobenzyloxy, 3-cyanobenzyloxy, 4-cyanobenzyloxy, 2-chlorobenzyloxy, 3-chlorobenzyloxy, 4-chlorobenzyloxy, 2-fluorobenzyloxy, 3-fluorobenzyloxy and 4-fluorobenzyloxy. 19. The compound according to claim 18, characterized in that R9a is H and R12a is H. The compound according to claim 19, characterized in that it has a structure that is a member selected from 21. The compound according to claim 20, characterized in that it has a structure that is a member selected from 25 25 22. A compound characterized in that it has a structure according to the following formula: where B is boron; L is a member selected from OR7, substituted or unsubstituted purine, substituted or unsubstituted pyrimidine, substituted or unsubstituted pyridine and substituted or unsubstituted imidazole; wherein R7 is a member selected from H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl; A is a member selected from OH, substituted or unsubstituted monophosphate, and substituted or unsubstituted phosphate, substituted or unsubstituted triphosphate, wherein Al is a nucleic acid sequence comprising between 1 and 100 nucleotides; Q is a member selected from substituted or unsubstituted heterocycloalkyl and substituted or unsubstituted heteroaryl; and Q comprises boron and at least one oxygen. 23. The compound according to claim 22, characterized in that the compound has a structure according to the following formula: where is a selected member of O and S; J is a member selected from (CR3aR4a) n? and CR5a; wherein R3a, R4a and R5a are members independently selected from H, halogen, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted aryl or unsubstituted and substituted or unsubstituted heteroaryl; nor is an integer selected from 0 to 2; W is a member selected from C = 0 (carbonyl), (CR6AR7a) m and CR8a; wherein R6a, R7a and R8a are members independently selected from H, halogen, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted heteroaryl or unsubstituted; m is an integer selected from 0 and 1; A is a selected member of CR9a and N; D is a member selected from CR10a and N; E is a selected member of CRlla and N; G is a member selected from CR12a and N; wherein R9a, R10a, Rlla and R12a are members independently selected from H, OR *, NR * R **, SR *, -S (0) R *, -S (0) 2R *, -S (0) 2NR * R **, -C (0) R *, -C (0) 0R *, -C (0) NR * R **, nitro, halogen, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, unsubstituted or substituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl; wherein each R * and R ** are members independently selected from H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl replaced; the combination of nitrogens (A + D + E + G) is an integer selected from 0 to 3; a member selected from R3a, R4a and R5a and a member selected from R6a, R7a and R8a, together with the atoms to which they are attached, optionally join to form a 4 to 7 membered ring; R3a and Ra, together with the atoms to which they are attached, optionally join to form a 4 to 7 membered ring; R6a and R7 ^ together with the atoms to which they are attached, optionally join to form a 4 to 7 membered ring; R9a and R10a, together with the atoms to which they are attached, optionally join to form a 4 to 7 membered ring; R10a and Rlla, together with the atoms to which they are attached, optionally join to form a 4- to 7-membered ring; Rlla and R12, together with the atoms to which they are attached, optionally join to form a 4- to 7-membered ring. 24. The compound according to claim 22, characterized in that it has a structure according to the following formula: 25. The compound according to claim 22, characterized in that it has a structure according to the following formula: 26. The compound according to claim 22, characterized in that R9a, R10a, Rlla and R12a are members independently selected from H, halogen, cyano, nitro, substituted or unsubstituted methoxy, substituted or unsubstituted methyl, substituted or unsubstituted ethoxy, ethyl substituted or unsubstituted, trifluoromethyl, substituted hydroxymethyl or unsubstituted, substituted hydroxyalkyl or unsubstituted, substituted or unsubstituted benzyl, substituted phenyl or unsubstituted phenyloxy substituted or unsubstituted, phenylmethoxy substituted or unsubstituted, tiofeniloxi substituted or unsubstituted pyridinyloxy substituted or unsubstituted pyrimidinyloxy substituted or unsubstituted, substituted or unsubstituted bencilfurano, substituted or unsubstituted methylthio, mercaptobencilo substituted or unsubstituted mercaptoalkyl substituted or unsubstituted, substituted or unsubstituted phenylthio, substituted or unsubstituted tiofeniltio, substituted phenylmethylthio or unsubstituted, pyridinylthio substituted on or, substituted pyrimidinylthio or unsubstituted, substituted benciltiofuranilo or unsubstituted, substituted phenylsulfonyl or unsubstituted, substituted benzylsulfonyl or unsubstituted, substituted phenylmethyl or unsubstituted, tiofenilsulfonilo substituted or unsubstituted, pyridinylsulfonyl substituted or unsubstituted, pirimidinilsulfonilo substituted or unsubstituted substituted sulfonamidyl or unsubstituted, substituted nilsulfinilo f or unsubstituted, substituted benzylsulfinyl or unsubstituted, substituted fenilmetilsulfinilo or unsubstituted, substituted tiofenilsulfinilo or unsubstituted, substituted pirimidinilsulfinilo or unsubstituted, substituted or unsubstituted amino, alkylamino substituted or unsubstituted, unsubstituted or substituted dialkylamino, substituted or unsubstituted trifluoromethylamino, substituted or unsubstituted aminomethyl, substituted or unsubstituted alkylaminomethyl, substituted or unsubstituted dialkylaminomethyl, substituted or unsubstituted arylaminomethyl, benzyl amino substituted or unsubstituted phenylamino substituted or unsubstituted, tiofenilamino substituted or unsubstituted, substituted pyridinylamino or unsubstituted, substituted pyrimidinylamino or unsubstituted indolyl substituted or unsubstituted morpholino substituted or unsubstituted alkylamido substituted or unsubstituted arylamido substituted or unsubstituted, substituted or unsubstituted ureido, substituted or unsubstituted carbamoyl and substituted or unsubstituted piperizinyl. 27. The compound according to claim 22, characterized in that R9a, R10a, Rlla and R12a are members independently selected from H, fluoro, chloro, bromo, nitro, cyano, amino, methyl, hydroxylmethyl, trifluoromethyl, methoxy, trifluoromethoxy, ethyl. , diethylcarbamoyl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, pyrimidinyl, piperazino, piperizinyl, piperizinocarbonilo, piperizinilcarbonilo, carboxyl, 1-tetrazolyl, 1-ethoxycarbonylmethoxy, carboxymethoxy, thiophenyl, 3- (butylcarbonyl) phenylmethoxy, lH-tetrazol-5-yl, 1-ethoxycarbonylmethyloxy-, 1-ethoxycarbonylmethyl-, 1-ethoxycarbonyl-, carboxymethoxy-, thiophen-2-yl, thiophen-2-ylthio-, thiophen-3-yl, thiophen-3 -thio, 4-fluorophenylthio, butylcarbonylphenylmethoxy, butylcarbonylphenylmethyl, butylcarbonylmethyl, 1- (piperidin-1-yl) carbonyl) methyl, 1- (piperidin-1-yl) carbonyl) methoxy, 1- (piperidin-2-yl) carbonyl) methoxy, 1- (piperidin-3-yl) carbonyl) methoxy, 1- (4- (pyrimidin-2-yl) piperazin-1-yl) carbonyl) methoxy, 1- (4- (pyrimidi n-2-yl) piperazin-1-yl) carbonyl) methyl, 1- (4- (pyrimidin-2-yl) piperazin-1-yl) carbonyl, 1-4- (pyrimidin-2-yl) piperazin-1 -yl, 1- (4- (pyridin-2-yl) piperazin-1-yl) carbonyl), 1- (4- (pyridin-2-yl) piperazin-1-yl) carbonylmethyl, (1- (4- (pyridin-2-yl) piperazin-1-yl) carbonyl) -methoxy), 1- (4- (pyridin-2-yl) piperazin-1-yl, 1 H -indol-1-yl, morpholino-, morpholinyl, morpholinocarbonyl, morpholinylcarbonyl, phenylureido, phenylcarbamoyl, acetamide, 3- (phenylthio) -lH-indol-1-yl, 3- (2-cyanoethylthio) -lH-indol-1-yl, benzylamino, 5-methoxy-3- (phenylthio) -lH-indol-1-yl, 5-methoxy-3- (2-cyanoethylthio) -lH-indol-1-yl), 5-chloro-lH-indol-1-yl, 5-chloro-3- ( 2-cyanoethylthio) -lH-indol-1-yl)), dibenzylamino, benzylamino, 5-chloro-3- (phenylthio) -lH-indol-1-yl), 4- (lH-tetrazol-5-yl) phenoxy, 4- (lH-tetrazol-5-yl) phenyl, 4- (lH-tetrazol-5-yl) phenylthio, 2-cyanophenoxy, 3-cyanophenoxy, 4-cyanophenoxy, 2-cyanophenylthio, 3-cyanophenylthio, 4- cyanophenylthio, 2-chlorophenoxy, 3-chlorophenoxy, 4-chlorophenoxy, 2-fluorophenoxy, 3-fluorophenoxy, 4-fluorophenoxy, 2-cyanobenzyloxy, 3-cyanobenzyloxy, 4-cyanobenzyloxy, 2-chlorobenzyloxy, 3-chlorobenzyloxy, 4-chlorobenzyloxy, 2-fluorobenzyloxy, 3-fluorobenzyloxy and 4-fluorobenzyloxy. 28. The compound according to claim 27, characterized in that it has a structure in accordance with 29. The compound according to claim 28, characterized in that it has a structure according to the following formula: 30. The compound of. according to claim 22, characterized in that L is a member selected from substituted or unsubstituted adenine, substituted or unsubstituted guanine, substituted or unsubstituted cytidine, unsubstituted or substituted uracil and unsubstituted or unsubstituted thi. 31. The compound according to claim 30, characterized in that L is adenine. 32. The compound according to claim 31, characterized in that the structure is a member selected from 33. The compound according to claim 32, characterized in that the Al is the nucleic acid sequence for a tRNA or a portion of the tRNA, and the t-RNA has a sequence that is a member selected from SEQ ID NOS: 18-62. 34. The compound according to claim 33, characterized in that the tRNA or the tRNA portion is a leucyl tRNA. 35. The compound according to claim 22, characterized in that it further comprises a tRNA synthetase, wherein the compound is non-covalently bound to the editing domain of the tRNA synthetase. 36. The compound according to claim 22, characterized in that it is present in a microorganism, with the proviso that the microorganism is not a member selected from Saccharomyces cerevisiae, Aspergillue niger, Peeudomonae aeruginoea, Staphylococcus aureus, Aureobasidium pullulane, Fuearium eolani, Penicillium pinophilum, Scopulariopeie brevicaulis, Streptoverticillium wakemanii, Al ternarla ternata, Cladoeporium herbarum, Phoma violacea, Stemphylium dentri ticum, Candida albicane, Eecherichia coli and Glioclaeium roeeum. 37. The compound according to claim 22, characterized in that it is present in a fungus, with the proviso that the fungus is not a selected member of Saccharomycee cerevieiae, Aepergillus niger, Fuearium eolani, Penicillium pinophilum, Scopulariopeis brevicaulis, Streptoverticillium wakemanii, It would alternate with the ternata, Cladosporium herbarum, Phoma violacea, Stemphylium dentri ticum, Candida albicane and Glioclaeium roseum. 38. The compound according to claim 22, characterized in that it is present in a microorganism that is a member selected from a dermatophyte, Trichophyton, Microeporum, Epidermophyton and yeast-type fungi. 39. The compound according to claim 36, characterized in that the microorganism is a member selected from Trichophyton spp. . 40. The compound according to claim 39, characterized in that the microorganism is a member selected from T. rubrum and T. menagrophytee. 41. The compound according to claim 22, characterized in that the compound is present in a human or an animal. 42. The compound according to claim 41, characterized in that it is present in a microorganism that is present in a human nail unit of a human or a nail, hoof or horn component of an animal. 43. The compound according to claim 22, characterized in that it is present in a selected member of dermatophyte, Trichophyton spp., Microeporum spp., Epidermophyton spp. and yeast type mushrooms. 44. The compound according to claim 36, characterized in that the microorganism is a member selected from Trichophyton species. 45. The compound according to claim 44, characterized in that the microorganism is a member selected from T. rubrum and T. menagrophytee. 46. Use of a compound which has a MIC of less than 16 μg / mL against the microorganism; a molecular weight of between approximately 100 Da and around 200 Da; a log P value of between about 1.0 and about 2.6; and a solubility in water of more than about 0.1 mg / mL octanol / water saturated in this way by killing or inhibiting the growth of the microorganism, for the manufacture of a medicament for inhibiting the growth, or killing, a microorganism present in a human nail component, wherein the human nail component comprises a nail plate and consists of contacting a back layer of the plate of the nail with a compound able to penetrate the nail plate and make contact with the microorganism, under sufficient conditions for the compound to penetrate the nail plate. 47. Use according to claim 46, wherein the compound comprises a boron-containing compound. 48. Use according to claim 46, wherein it has a structure according to the formula where B is boron; Rla is a member selected from a negative charge, a salt counterion, H, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and heteroaryl substituted or unsubstituted; M is a selected member of oxygen, sulfur and NR2a; R2a is a member selected from H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl; J is a member selected from (CR3aR4a) n? and CR5a; R3a, Ra and R5a are members independently selected from H, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl; nor is an integer selected from 0 to 2; W is a member selected from C = 0 (carbonyl), (CR6aR7a) m? and CR8a; R6a, R7a and R8a are members independently selected from H, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl; ml is an integer selected from 0 and 1; A is a selected member of CR9 and N; D is a member selected from CR10a and N; E is a selected member of CRlla and N; G is a member selected from CR12a and N; wherein R9a, R10a, Rlla and R12a are members independently selected from H, OR *, NR * R **, SR *, S (0) R *, -S (0) 2R *, -S (0) 2NR * R **, -C (0) R *, -C (0) OR *, C (0) NR * R **, nitro, halogen, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted cycloalkyl or unsubstituted, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl; the combination of nitrogens (A + D + E + G) is an integer selected from 0 to 3; each R * and R ** are members independently selected from H, nitro, halogen, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl; a member selected from R3a, Ra and R5a and a member selected from R6a, R7a and R8a, together with the atoms to which they are attached, optionally join to form a 4- to 7-membered ring; R3a and R4a, together with the atoms to which they are attached, optionally join to form a 4 to 7 membered ring; R6a and R7a, together with the atoms to which they are attached, optionally join to form a 4 to 7 membered ring; R9a and R10a, together with the atoms to which they are attached, optionally join to form a 4 to 7 membered ring; R10a and Rlla, together with the atoms to which they are attached, optionally join to form a 4- to 7-membered ring; Rll and R12a, together with the atoms to which they are attached, optionally join to form a 4 to 7 membered ring. 49. Use according to claim 48, wherein R9a, R10a, Rll and R12a are members independently selected from H, halogen, cyano, nitro, substituted or unsubstituted methoxy, substituted or unsubstituted methyl, substituted or unsubstituted ethoxy, unsubstituted or substituted ethyl, trifluoromethyl, substituted or unsubstituted hydroxymethyl, substituted or unsubstituted hydroxyalkyl, substituted or unsubstituted benzyl, unsubstituted or substituted phenyl, unsubstituted or substituted phenyloxy, unsubstituted or substituted phenylmethoxy, unsubstituted or substituted thiophenyloxy, substituted or unsubstituted pyridinyloxy, substituted or unsubstituted pyrimidinyloxySubstituted bencilfurano or unsubstituted, substituted or unsubstituted methylthio, I mercaptobencilo substituted or unsubstituted, mercaptoalkyl substituted or unsubstituted, substituted phenylthio or unsubstituted, substituted tiofeniltio or unsubstituted, substituted phenylmethylthio or unsubstituted, substituted pyridinylthio or unsubstituted pyrimidinylthio substituted or unsubstituted, substituted benciltiofuranilo or unsubstituted, substituted phenylsulfonyl or unsubstituted, substituted benzylsulfonyl or unsubstituted, substituted phenylmethyl or unsubstituted tiofenilsulfonilo substituted or unsubstituted pyridinylsulfonyl substituted or unsubstituted, pirimidinilsulfonilo substituted or unsubstituted sulfonamidyl substituted or unsubstituted, substituted or unsubstituted phenylsulfinyl, substituted or unsubstituted benzylsulfinyl, unsubstituted or substituted phenylmethylsulphinyl, substituted or unsubstituted thiophenylsulfinyl, substituted or unsubstituted pyrimidinyl-sulfinyl, substituted or unsubstituted amino, alkylamino substituted or unsubstituted dialkylamino substituted or unsubstituted trifluoromethylamino substituted or unsubstituted aminomethyl substituted or unsubstituted, alkylaminomethyl substituted or unsubstituted, dialkylaminomethyl substituted or unsubstituted, arilaminometilo substituted or unsubstituted, substituted benzylamino or unsubstituted, substituted phenylamino or unsubstituted, substituted tiofenilamino or unsubstituted, pyridinylamino substituted or unsubstituted, substituted pyrimidinylamino or unsubstituted indolyl substituted or unsubstituted, substituted morpholino or unsubstituted alkylamido substituted or unsubstituted arylamido substituted or unsubstituted ureido substituted or substituted, substituted or unsubstituted carbamoyl and substituted or unsubstituted piperizinyl. 50. Use according to claim 48, wherein R9a, R10a, Rlla and R12a are members independently selected from H, fluoro, chloro, bromo, nitro, cyano, amino, methyl, hydroxylmethyl, trifluoromethyl, methoxy, trifluoromethoxy, ethyl, diethylcarbamoyl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, pyrimidinyl, piperazino, piperizinyl, piperizinocarbonilo, piperizinilcarbonilo, carboxyl, 1-tetrazolyl, 1-ethoxycarbonylmethoxy, carboxymethoxy, thiophenyl, 3- (butylcarbonyl) phenylmethoxy thiophen-2-yl, 1H-tetrazol-yl-5, 1-ethoxycarbonylmethyl? i-, 1-etoxicarbonilmetilo-, 1-etoxicarbonilo-, carboximetoxi-, thiophen-2-iltio-, thiophen-3-yl, -thiophene 3-ilthio, 4-fluorophenylthio, butylcarbonylphenylmethoxy, butylcarbonylphenylmethyl, butylcarbonylmethyl, 1- (piperidin-1-yl) carbonyl) methyl, 1- (piperidin-1-yl) carbonyl) methoxy, 1- (piperidin-2-yl) carbonyl) methoxy, - (piperidin-3-yl) carbonyl) methoxy, 1- (4- (pyrimidin-2-yl) piperazin-1-yl) carbonyl) methoxy, 1- (4- (pyrimidin-2-yl) piperazine-1- il) carbonyl) methyl, 1- (4- (pyrimidin-2-yl) piperazin-1-yl) carbonyl, 1-4- (pyrimidin-2-yl) piperazin-1-yl, 1- (4- (pyridine -2-yl) piperazin-1-yl) carbonyl), 1- (4- (pyridin-2-yl) piperazin-1-yl) carbonylmethyl, (1- (4- (pyridin-2-yl) piperazine-1 -yl) carbonyl) -methoxy), 1- (4- (pyridin-2-yl) piperazin-1-yl, lH-indol-1-yl, morpholino-, morpholinyl, morpholinocarbonyl, morpholinylcarbonyl, phenylureido, phenylcarbamoyl, acetamide, 3- (phenylthio) -lH-indol-1-yl, 3- (2-cyanoethylthio) -lH-indol-1-yl, benzylamino, 5-methoxy-3- (phenylthio) -lH-indol-1-yl, 5-methoxy-3- (2-cyanoethylthio) -1H-indol-1-yl), 5-chloro-lH-indol-1-yl, 5-chloro-3- (2-cyanoethylthio) -lH-ind ol-1-yl)), dibenzylamino, benzylamino, 5-chloro-3- (phenylthio) -lH-indol-1-yl)), 4- (lH-tetrazol-5-yl) phenoxy, 4- (lH-) tetrazol-5-yl) phenyl, 4- (lH-tetrazol-5-yl) phenylthio, 2-cyanophenoxy, 3-cyanophenoxy, 4-cyanophenoxy, 2-cyanophenylthio, 3-cyanophenylthio, 4-cyanophenylthio, 2-chlorophenoxy, 3 -chlorophenoxy, 4-chlorophenoxy, 2-fluorophenoxy, 3-fluorophenoxy, 4-fluorophenoxy, 2-cyanobenzyloxy, 3-cyanobenzyloxy, 4-cyanobenzyloxy, 2-chlorobenzyloxy, 3-chlorobenzyloxy, 4-chlorobenzyloxy, 2-fluorobenzyloxy, 3-fluorobenzyloxy and 4-fluorobenzyloxy. 51. Use according to claim 49, wherein R9a is H and R12a is H. 52. Use according to claim 48, wherein the compound is 1,3-dihydro-5-fluoro-l-hydroxy-2. , 1-benzoxazole. 53. Use of a compound having a MIC of less than 16 μg / mL against a microorganism; a molecular weight of between about 100 Da and about 200 Da; a log P value of between about 1.0 and about 2.6; and a solubility in water of more than about 0.1 mg / mL octanol / water, for the manufacture of a medicament for treating a disease caused by a microorganism present in a human nail component, wherein the human nail component comprises a plate of nail and consists in contacting a dorsal layer of the nail plate with the compound able to penetrate the nail plate and make contact with the microorganism, under conditions sufficient for the compound to penetrate the nail plate. 54. Use according to claim 53, wherein the compound has a structure in accordance with the formula: where B is boron; Rla is a member selected from a negative charge, a salt counterion, H, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and heteroaryl substituted or unsubstituted; M is a selected member of oxygen, sulfur and NR2a; R2a is a member selected from H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl; J is a member selected from (CR3aRa) n? and CR5a; R3, R4a and R5a are members independently selected from H, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl; nor is an integer selected from 0 to 2; W is a member selected from C = 0 (carbonyl), (CR6aR7a) ra? and CR8a; R6a, R7a and R8 are members independently selected from H, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl; ml is an integer selected from 0 and 1; A is a selected member of CR9a and N; D is a member selected from CR10a and N; E is a selected member of CRlla and N; G is a member selected from CR12a and N; wherein R9a, R10a, Rlla and R12a are members independently selected from H, OR *, NR * R **, SR *, S (0) R *, -S (0) 2R *, -S (0) 2NR * R **, -C (0) R *, -C (0) OR *, C (0) NR * R **, nitro, halogen, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl replaced; the combination of nitrogens (A + D + E + G) is an integer selected from 0 to 3; each R * and R ** are members independently selected from H, nitro, halogen, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl; a member selected from R3a, R4a and R5a and a member selected from R6a, R7a and R8a, together with the atoms to which they are attached, optionally join to form a 4 to 7 membered ring; R3a and R4a, together with the atoms to which they are attached, optionally join to form a 4 to 7 membered ring; R6a and R7a, together with the atoms to which they are attached, optionally join to form a 4 to 7 membered ring; R9a and R10a, together with the atoms to which they are attached, optionally join to form a 4 to 7 membered ring; R10a and Rlla, together with the atoms to which they are attached, optionally join to form a 4- to 7-membered ring; Ria and Ri2a ^ together with the atoms to which they are attached, optionally join to form a 4 to 7 member ring. 55. Use according to claim 54, wherein R9a, R10a, Rlla and R12a are members independently selected from H, halogen, cyano, nitro, substituted or unsubstituted methoxy, substituted or unsubstituted methyl, substituted or unsubstituted ethoxy, unsubstituted or substituted ethyl, trifluoromethyl, substituted or unsubstituted hydroxymethyl, substituted or unsubstituted hydroxyalkyl, substituted or unsubstituted benzyl, unsubstituted or substituted phenyl, unsubstituted or substituted phenyloxy, unsubstituted or substituted phenylmethoxy, unsubstituted or substituted thiophenyloxy, substituted or unsubstituted pyridinyloxy, substituted or unsubstituted pyrimidinyloxy, substituted or unsubstituted benzylfuran, unsubstituted or substituted methylthio, unsubstituted or substituted mercaptobenzyl, substituted or unsubstituted mercaptoalkyl, substituted or unsubstituted phenylthio, unsubstituted or substituted thiophenthio, substituted phenylmethylthio or unsubstituted, substituted or unsubstituted pyridinylthio, py unsubstituted or substituted imidinylthio, unsubstituted or substituted benzylthiuram, unsubstituted or substituted phenylsulfonyl, substituted or unsubstituted benzylsulfonyl, unsubstituted or substituted phenylmethylsulfonyl, unsubstituted or substituted thiophenylsulfonyl, unsubstituted or substituted pyridinylsulfonyl, unsubstituted or substituted pyrimidinylsulfonyl, substituted sulfonamidyl or unsubstituted, substituted or unsubstituted phenylsulfinyl, substituted or unsubstituted benzylsulfinyl, unsubstituted or substituted phenylmethylsulphinyl, substituted or unsubstituted thiophenylsulfinyl, substituted or unsubstituted pyrimidinylsulfinyl, unsubstituted or substituted amino, substituted or unsubstituted alkylamino, substituted or unsubstituted dialkylamino substituted, substituted or unsubstituted trifluoromethylamino, substituted or unsubstituted aminomethyl, substituted or unsubstituted alkylaminomethyl, substituted or unsubstituted dialkylaminomethyl, substituted or unsubstituted arylaminomethyl, substituted benzylamino or unsubstituted, substituted or unsubstituted phenylamino, substituted or unsubstituted thiophenylamino, substituted or unsubstituted pyridinylamino, substituted or unsubstituted pyrimidinylamino, substituted or unsubstituted indolyl, substituted or unsubstituted morpholino, substituted or unsubstituted alkylamido, substituted or unsubstituted arylamido, substituted or unsubstituted ureido, substituted or unsubstituted carbamoyl and substituted or unsubstituted piperizinyl. 56. Use according to claim 54, wherein R9a, R10, Rlla and R12a are members independently selected from H, fluoro, chloro, bromo, nitro, cyano, amino, methyl, hydroxylmethyl, trifluoromethyl, methoxy, trifluoromethoxy, ethyl, diethylcarbamoyl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, pyrimidinyl, piperazino, piperizinyl, piperizinocarbonyl, piperizinylcarbonyl, carboxyl, 1-tetrazolyl, 1-ethoxycarbonylmethoxy, carboxymethoxy, thiophenyl, 3- (butylcarbonyl) phenylmethoxy , 1H-tetrazol-5-yl, 1-ethoxycarbonylmethyloxy-, 1-ethoxycarbonylmethyl-, 1-ethoxycarbonyl-, carboxymethoxy-, thiophen-2-yl, thiophen-2-ylthio-, thiophen-3-yl, thiophen-3- iltio, 4-fluorophenylthio, butylcarbonylphenylmethoxy, butylcarbonylphenylmethyl, butylcarbonylmethyl, 1- (piperidin-1-yl) carbonyl) methyl, 1- (piperidin-1-yl) carbonyl) ethoxy, 1- (piperidin-2-yl) carbonyl) methoxy , 1- (piperidin-3-yl) carbonyl) methoxy, 1- (4- (pyrimidin-2-yl) piperazin-1-yl) carbonyl) methoxy, 1- (4- (pyrimidin-2-yl) piperazine- 1-yl) carbonyl) methyl, 1- (4- (pyrimidin-2-yl) piperazin-1-yl) carbonyl, 1-4- (pyrimidin-2-yl) piperazin-1-yl, 1- (4- (pyridin-2-yl) piperazin-1-yl) carbonyl), 1- (4- (pyridin-2-yl) piperazin-1-yl) carbonylmethyl, (1- (4- (pyridin-2-yl) piperazin-1-yl) carbonyl) -methoxy), 1- (4- (pyridin-2-yl) piperazin-1-yl, 1H-indole-1-yl, morpholino-, morpholinyl, morpholinecarbonyl, morpholinylcarbonyl, phenylureido, phenylcarbamoyl, acetamide, 3- (f-enyl thio) -lH-indol-1-yl, 3- (2-cyanoethylthio) -lH-indol-1-yl, benzylamino, 5-methoxy-3- (phenyl thio) -1H- indol-1-yl, 5-methoxy-3- (2-cyanoethylthio) -lH-indol-1-yl), 5-chloro-lH-indol-l-yl, 5-chloro-3- ( 2-cyanoethylthio) -lH-indol-1-yl)), dibenzylamino, benzylamino, 5-chloro-3- (phenylthio) -1H-indol-1-yl), 4- (1H-tetrazol-5-yl) phenoxy, 4- (lH-tetrazol-5-yl) phenyl, 4- (1H-tetrazol-5-yl) f-enyl thio, 2-cyanophenoxy, 3-cyano-enoxy, 4-cyano-enoxy, 2-cyanofenyl thio, 3-cyanofenyl thio, 4-cyanofenyl thio, 2-chlorofenoxi, 3-chlorofenoxi, 4-chlorofenoxi, 2-f luorofenoxi, 3-f luorofenoxi, 4-f luorofenoxi, 2-cyanobenzyloxy, 3-cyanobenzyloxy, 4-cyanobenzyloxy, 2-chlorobenzyloxy, 3 -chlorobenzyloxy, 4-chlorobenzyloxy, 2-f luorobenzyloxy, 3-f luorobenzyloxy and 4-f luorobenzyloxy. 57. Use according to claim 55, wherein R9a is H and R12a is H. 58. Use according to claim 54, wherein the compound is 1,3-dihydro-5-fluoro-l-hydroxy-2, 1-benzoxazole. 59. Use of a compound having a coefficient of effectiveness above 10, wherein the compound is supplied from the dorsal layer of the nail plate to the nail bed and consists of contacting the cell with the compound capable of penetrating the nail bed. nail plate, under conditions sufficient to penetrate the nail. 60. Use according to claim 59, wherein the compound comprises boron. 61. Use of a compound having a coefficient of effectiveness greater than 10, for the manufacture of a medicament for treating a disease caused by a microorganism present in a human nail unit, wherein the human nail unit comprises a plate of the nail, which comprises: contacting a dorsal plate of the nail plate with the compound capable of penetrating the nail plate, under conditions sufficient for the compound to penetrate the nail plate and treat the disease 62. according to claim 61, wherein the compound has a structure in accordance with the formula: where B is boron; Rla is a member selected from a negative charge, a salt counterion, H, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and heteroaryl substituted or unsubstituted; M is a selected member of oxygen, sulfur and NR2a; R2a is a member selected from H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl; J is a member selected from (CR3aR4a) n? and CR5a; R3a, Ra and R5a are members independently selected from H, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl; nor is an integer selected from 0 to 2; W is a member selected from C = 0 (carbonyl), (CR6aR7a) ml and CR8a; R6a, R7a and R8a are members independently selected from H, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl; ml is an integer selected from 0 and 1; A is a selected member of CR9a and N; D is a member selected from CR10a and N; E is a selected member of CRlla and N; G is a member selected from CR12a and N; wherein R9, R10a, Rlla and R12a are members independently selected from H, OR *, NR * R **, SR *, S (0) R *, -S (0) 2R *, -S (0) 2NR * R **, -C (0) R *, -C (0) OR *, C (0) NR * R **, nitro, halogen, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted cycloalkyl or unsubstituted, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl; the combination of nitrogens (A + D + E + G) is an integer selected from 0 to 3; each R * and R ** are members independently selected from H, nitro, halogen, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl; a member selected from R3a, Ra and R5a and a member selected from R6a, R7a and R8a, together with the atoms to which they are attached, optionally join to form a 4- to 7-membered ring; R3a and Ra, together with the atoms to which they are attached, optionally join to form a ring of 4 to 7 members; R6a and R7, together with the atoms to which they are attached, optionally join to form a 4 to 7 membered ring; R9a and R10a, together with the atoms to which they are attached, optionally join to form a 4 to 7 membered ring; R10a and Rlla, together with the atoms to which they are attached, optionally join to form a 4- to 7-membered ring; Rlla and R12a, together with the atoms to which they are attached, optionally join to form a 4- to 7-membered ring. 63. Use according to claim 62, wherein R9a, R10a, Rlla and R12a are members independently selected from H, halogen, cyano, nitro, substituted or unsubstituted methoxy, substituted or unsubstituted methyl, substituted or unsubstituted ethoxy, unsubstituted or substituted ethyl, trifluoromethyl, substituted or unsubstituted hydroxymethyl, substituted or unsubstituted hydroxyalkyl, substituted or unsubstituted benzyl, substituted or unsubstituted phenyl, unsubstituted or substituted phenyloxy, unsubstituted or substituted phenylmethoxy, unsubstituted or substituted thiophenyloxy, substituted or unsubstituted pyridinyloxy, substituted or unsubstituted pyrimidinyloxy, substituted or unsubstituted benzylfuran, unsubstituted or substituted methylthio, unsubstituted or substituted mercaptobenzyl, substituted or unsubstituted mercaptoalkyl, substituted or unsubstituted phenylthio, unsubstituted or substituted thiophenthio, substituted phenylmethylthio or unsubstituted, substituted or unsubstituted pyridinylthio, py unsubstituted or substituted imidinylthio, unsubstituted or substituted benzylthiuram, unsubstituted or substituted phenylsulfonyl, substituted or unsubstituted benzylsulfonyl, unsubstituted or substituted phenylmethylsulfonyl, unsubstituted or substituted thiophenylsulfonyl, unsubstituted or substituted pyridinylsulfonyl, unsubstituted or substituted pyrimidinylsulfonyl, substituted sulfonamidyl or unsubstituted, substituted or unsubstituted phenylsulfinyl, unsubstituted or substituted benzylsulfinyl, substituted or unsubstituted phenyl-substituted or unsubstituted phenyl-substituted or unsubstituted thiophenesulfyl, substituted or unsubstituted pyrimidinyl-substituted or unsubstituted amino, unsubstituted or substituted alkylamino substituted, unsubstituted or substituted dialkylamino, substituted or unsubstituted trifluoromethylamino, substituted or unsubstituted aminomethyl, substituted or unsubstituted alkylaminomethyl, substituted or unsubstituted dialkylaminomethyl, substituted or unsubstituted arylaminomethyl, benzylamino-substituted unsubstituted or substituted, substituted or unsubstituted phenylamino, substituted or unsubstituted thiophenylamino, substituted or unsubstituted pyridinylamino, substituted or unsubstituted pyrimidinylamino, unsubstituted or substituted indolyl, substituted or unsubstituted morpholino, substituted or unsubstituted alkylamido, substituted arylamido or unsubstituted, substituted or unsubstituted ureido, substituted or unsubstituted carbamoyl and substituted or unsubstituted piperizinyl. 64. Use according to claim 62, wherein R9a, R10a, Rlla and R12a are members independently selected from H, fluoro, chloro, bromo, nitro, cyano, amino, methyl, hydroxylmethyl, trifluoromethyl, methoxy, trifluoromethoxy, ethyl, diethylcarbamoyl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, pyrimidinyl, piperazino, piperizinyl, piperizinocarbonyl, piperizinylcarbonyl, carboxyl, 1-tetrazolyl, 1-ethoxycarbonylmethoxy, carboxymethoxy, thiophenyl, 3- (butylcarbonyl) Phenylmethoxy, 1H-tetrazol-5-yl, 1-ethoxycarbonylmethyloxy-, 1-ethoxycarbonylmethyl-, 1-ethoxycarbonyl-, carboxymethoxy-, thiophen-2-yl, thiophen-2-ylthio-, thiophen-3-yl, thiophen-3 -yl thio, 4-fluorophenyl thio, butylcarbonylphenylmethoxy, butylcarbonylphenylmethyl, butylcarbonylmethyl, 1- (piperidin-1-yl) carbonyl) methyl, 1- (piperidin-1-yl) carbonyl) methoxy, 1- (piperidin-2-yl) carbonyl) methoxy, 1- (piperidin-3-yl) carbonyl) me oxy, 1- (4- (pyrimidin-2-yl) piperazin-1-yl) carbonyl) methoxy, - (4- (Pyrimidin-2-yl) piperazin-1-yl) carbonyl) methyl, 1- (4- (pyrimidin-2-yl) piperazin-1-yl) carbonyl, l-4- (pyrimidin-2-yl) piperazin-1-yl, 1- (4- (pyridin-2-yl) piperazin-1-yl) carbonyl), 1- (4- (pyridin-2-yl) piperazin-1-yl) carbonylmethyl, (1- (4- (pyridin-2-yl) piperazin-1-yl) carbonyl) -methoxy), 1- (4- (pyridin-2-yl) piperazin-1-yl, 1H-indol-1-yl, morpholino-, morpholinyl, morpholinocarbonyl, morpholinylcarbonyl, phenylureido, phenylcarbamoyl, acetamide, 3- (phenylthio) -lH-indol-1-yl, 3- (2-cyanoethylthio) -lH-indol-1-yl, benzylamino, 5-methoxy-3- (phenylthio) -lH-indol-1-yl, 5-methoxy-3 - (2-cyanoethylthio) -lH-indol-1-yl)), 5-chloro-lH-indol-1-yl, 5-chloro-3- (2-cyanoethylthio) -lH-indol-1-yl)) , dibenzylamino, benzylamino, 5-chloro-3- (phenylthio) -lH-indol-1-yl), 4- (lH-tetrazol-5-yl) phenoxy, 4- (lH-tetrazol-5-yl) phenyl 4- (lH-tetrazol-5-yl) phenylthio, 2-cyanophenoxy, 3-cyanophenoxy, 4-cyanophenoxy, 2-cyanophenylthio, 3-cyanophenylthio, 4-cyanophenylthio, 2-chlorophenoxy, 3-chlorophenoxy, 4-chlorophenoxy, 2-fluorophenoxy, 3-fluorophenoxy, 4- fluorophenoxy, 2-cyanobenzyloxy, 3-cyanobenzyloxy, 4-cyanobenzyloxy, 2-chlorobenzyloxy, 3-chlorobenzyloxy, 4-chlorobenzyloxy, 2-fluorobenzyloxy, 3-fluorobenzyloxy and 4-fluorobenzyloxy. 65. Use according to claim 63, wherein R9a is H and R12a is H. 66. Use according to claim 65, wherein the compound is 1,3-dihydro-5-fluoro-1-hydroxy-2. , 1-benzoxazole. 67. A formulation characterized in that it comprises: (a) a compound that is a member selected from a boron-containing compound, a compound that contains 2'-amino ribofuranose, a compound containing 3'-amino ribofuranose and combinations thereof and (b) a keratin-containing component which is a selected member of a human nail, skin and hair unit, wherein the compound of part (a) makes contact with the component of part (b). 68. The formulation according to claim 67, characterized in that the keratin-containing component is a nail plate of the human nail unit. 69. The formulation according to claim 67, characterized in that the keratin-containing component is a nail bed of the human nail unit. 70. The formulation according to claim 67, characterized in that the compound is present in the formulation at a concentration which is a selected member of about 0.001%, about 0.01%, about 0.05%, about 0.1%, about 0.5. %, approximately 15, around 1.5%, approximately 2%, around 2.5%, approximately 3%. 71. The formulation according to claim 67, characterized in that the keratin-containing compound is present in the formulation at a concentration that is a selected member of about 99. 99%, approximately 99.95%, around 99.90%, approximately 99.5%, around 99.0%, approximately 98.5%, around 98.0%, approximately 97.5% and around 97%. 72. The formulation according to claim 67, characterized in that the compound is a boron-containing compound. 73. The formulation according to claim 72, characterized in that the boron-containing compound is a member selected from cyclic boronic ester and cyclic borinic ester. 74. The formulation according to claim 67, characterized in that the compound has a structure according to the formula: where B is boron; Rla is a member selected from a negative charge, a salt counterion, H, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and heteroaryl substituted or unsubstituted; M is a selected member of oxygen, sulfur and NR2a; R is a member selected from H, substituted or unsubstituted algeryl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl; J is a member selected from (CR3aR4a) ni and CR5a; R3a, R4a and R5a are members independently selected from H, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl; nor is an integer selected from 0 to 2; W is a member selected from C = 0 (carbonyl), (CR6aR7a) ml and CR8a; R6a, R7a and R8a are members independently selected from H, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl; ml is an integer selected from 0 and 1; A is a selected member of CR9a and N; D is a member selected from CR10a and N; E is a selected member of CRlla and N; G is a member selected from CR12a and N; wherein R9a, R10a, Rlla and R12a are members independently selected from H, OR *, NR * R **, SR *, S (0) R *, -S (0) 2R *, -S (0) 2NR * R **, -C (0) R *, -C (0) OR *, C (0) NR * R **, nitro, halogen, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted cycloalkyl or unsubstituted, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl; the combination of nitrogens (A + D + E + G) is an integer selected from 0 to 3; each R * and R ** are members independently selected from H, nitro, halogen, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl; a member selected from R3a, R4a and R5a and a member selected from R6a, R7a and R8a, together with the atoms to which they are attached, optionally join to form a 4 to 7 membered ring; R3a and R, together with the atoms to which they are attached, optionally join to form a 4 to 7 membered ring; R6 and R7a, together with the atoms to which they are attached, optionally join to form a 4 to 7 membered ring; R9 and R10a, together with the atoms to which they are attached, optionally join to form a 4 to 7 membered ring; R10a and Rll, together with the atoms to which they are attached, optionally join to form a 4 to 7 membered ring; R ia and Ri2a ^ jun or with the atoms to which they are attached, optionally join to form a ring of 4 to 7 members. 75. The formulation according to claim 74, characterized in that R9a, R10a, Rlla and R12a are members independently selected from H, halogen, cyano, nitro, substituted or unsubstituted methoxy, substituted or unsubstituted methyl, substituted or unsubstituted ethoxy, substituted or unsubstituted ethyl, trifluoromethyl, hydroxymethyl substituted or unsubstituted, substituted hydroxyalkyl or unsubstituted, substituted or unsubstituted benzyl, substituted or unsubstituted phenyl, phenyloxy substituted or unsubstituted, phenylmethoxy substituted or unsubstituted, tiofeniloxi substituted or unsubstituted, pyridinyloxy substituted or unsubstituted, substituted pyrimidinyloxy or unsubstituted, substituted bencilfurano or unsubstituted, substituted methylthio or unsubstituted mercaptóbencilo substituted or unsubstituted mercaptoalkyl substituted or unsubstituted, substituted phenylthio or unsubstituted, substituted tiofeniltio or unsubstituted, substituted phenylmethylthio or unsubstituted, substituted pyridinylthio or unsubstituted , substituted or unsubstituted pyrimidinylthio gone, replaced benciltiofuranilo or not, substituted phenylsulfonyl or not, substituted or unsubstituted benzylsulfonyl substituted or unsubstituted phenylmethylsulfonyl, substituted or unsubstituted tiofenilsulfonilo, substituted or unsubstituted -pyridinylsulfonyl, substituted or unsubstituted pirimidinilsulfonilo, substituted sulfonamidyl or unsubstituted, phenylsulfinyl substituted or unsubstituted, substituted benzylsulfinyl or unsubstituted, substituted fenilmetilsulfinilo or unsubstituted, tiofenilsulfinilo substituted or unsubstituted, pirimidinilsulfinilo substituted or unsubstituted, substituted or unsubstituted amino, alkylamino substituted or unsubstituted, substituted or unsubstituted dialkylamino, unsubstituted trifluoromethylamino substituted or unsubstituted, substituted or unsubstituted aminomethyl, substituted or unsubstituted alkylaminomethyl, substituted or unsubstituted dialkylaminomethyl, substituted or unsubstituted arylaminomethyl, substituted or unsubstituted benzylamino, substituted phenylamino gone or unsubstituted, substituted tiofenilamino or unsubstituted, pyridinylamino substituted or unsubstituted, substituted pyrimidinylamino or unsubstituted indolyl substituted or unsubstituted, substituted morpholino or unsubstituted alkylamido substituted or unsubstituted arylamido substituted or unsubstituted ureido substituted or unsubstituted, substituted or unsubstituted carbamoyl and substituted or unsubstituted piperizinyl. 76. The formulation according to claim 74, characterized in that R9a, R10a, Rlla and R12a are members independently selected from H, fluoro, chloro, bromo, nitro, cyano, amino, methyl, hydroxylmethyl, trifluoromethyl, methoxy, trifluoromethoxy, ethyl. , diethylcarbamoyl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, pyrimidinyl, piperazino, piperizinyl, piperizinocarbonilo, piperizinilcarbonilo, carboxyl, 1-tetrazolyl, 1-ethoxycarbonylmethoxy, carboxymethoxy, thiophenyl, 3- (butylcarbonyl) phenylmethoxy, lH-tetrazol-5-yl, 1-ethoxycarbonylmethyloxy-, 1-ethoxycarbonylmethyl-, 1-ethoxycarbonyl-, carboxymethoxy-, thiophen-2-yl, thiophen-2-ylthio-, thiophen-3-yl, thiophen-3 -thio, 4-fluorophenylthio, butylcarbonylphenylmethoxy, butylcarbonylphenylmethyl, butylcarbonylmethyl, 1- (piperidin-1-yl) carbonyl) methyl, 1- (piperidin-1-yl) carbonyl) methoxy, 1- (piperidin-2-yl) carbonyl) methoxy, 1- (piperidin-3-yl) carbonyl) methoxy, 1- (4- (pyrimidin-2-yl) piperazin-1-yl) carbonyl) methoxy, 1- (4- (pyrim idin-2-yl) piperazin-1-yl) carbonyl) methyl, 1- (4- (pyrimidin-2-yl) piperazin-1-yl) carbonyl, 1-4- (pyrimidin-2-yl) piperazin-1 -yl, 1- (4- (pyridin-2-yl) piperazin-1-yl) carbonyl), 1- (4- (pyridin-2-yl) piperazin-1-yl) carbonylmethyl, (1- (4- (pyridin-2-yl) piperazin-1-yl) carbonyl) -methoxy), 1- (4- (pyridin-2-yl) piperazin-1-yl, 1 H -indol-1-yl, morpholino-, morpholinyl, morpholinocarbonyl, morpholinylcarbonyl, phenylureido, phenylcarbamoyl, acetamide, 3- (phenylthio) -lH-indol-1-yl, 3- (2-cyanoethylthio) -lH-indol-1-yl, benzylamino, 5-methoxy-3- (phenyl) ) -lH-indol-1-yl, 5-methoxy-3- (2-cyanoethylthio) -lH-indol-1-yl)), 5-chloro-lH-indol-1-yl, 5-chloro-3- (2-cyanoethylthio) -lH-indol-1-yl), dibenzylamino, benzylamino, 5-chloro-3- (phenylthio) -lH -indol-1-yl)), 4- (lH-tetrazol-5-yl) phenoxy, 4- (lH-tetrazol-5-yl) phenyl, 4- (lH-tetrazol-5-yl) phenylthio, 2- cyanophenoxy, 3-cyanophenoxy, 4-cyanophenoxy, 2-cyanophenylthio, 3-cyanophenylthio, 4-cyanophenylthio, 2-chlorophenoxy, 3-chlorophenoxy, 4-chlorophenoxy, 2-fluorophenoxy, 3-fluorophenoxy, 4-fluorophenoxy, 2-cyanobenzyloxy, 3-cyanobenzyloxy, 4-cyanobenzyloxy, 2-chlorobenzyloxy, 3-chlorobenzyloxy, 4-chlorobenzyloxy, 2-fluorobenzyloxy, 3-fluorobenzyloxy and 4-fluorobenzyloxy. 77. The formulation according to claim 75, characterized in that R9a is H and R12a is H. 78. The formulation according to claim 74, characterized in that the compound is 1,3-dihydro-5-fluoro-l-hydroxy-2. , 1-benzoxazole. 79. A method for inhibiting the conversion of an ARMt molecule into a charged tRNA molecule, characterized by comprising: contacting a tRNA synthetase with a compound effective to inhibit the activity of an editing domain of the tRNA synthetase, under conditions sufficient to inhibit the activity, thereby inhibiting the conversion wherein the compound comprises a member selected from a cyclic boronic ester, cyclic borinic ester, 2'-amino ribofuranose portion and a 3'-amino ribofuranose portion. 80. The method of compliance with the claim 79, characterized in that the inhibition occurs within a microorganism. 81. The method of compliance with the claim 80, characterized in that the microorganism is a selected member of bacteria, fungi, yeast and parasites. 82. The method according to claim 79, characterized in that the tRNA synthetase a member selected from a mitochondrial tRNA synthetase and cytoplasmic tRNA synthetase. 83. The method according to claim 82, characterized in that the tRNA synthetase is a member selected from alanyl tRNA synthetase, isoleucyl tRNA synthetase, leucyl tRNA synthetase, methionyl tRNA synthetase, lysyl tRNA synthetase, phenylalanyl tRNA synthetase, prolyl tRNA synthetase, threonil TRNA synthetase and valil tRNA synthetase. 84. The method according to claim 79, characterized in that the compound has a KD, synthesis of more than 100 μM against a synthetic domain of the tRNA synthetase. 85. The method according to claim 84, characterized in that the ratio of a minimum concentration of the compound that inhibits the editing domain to a minimum concentration of the compound that inhibits the synthetic domain of the tRNA synthetase, represented as KD, edition / KD , synthesis, is less than one. 86. The method according to claim 85, characterized in that the KD / edition / KD, synthesis of the compound is a selected member of less than 0.5, less than 0.1 and less than 0.05. 87. The method according to claim 79, characterized in that the 2'-amino ribofuranose portion has a structure according to the following formula: and the 3'-amino-ribofuranose portion has a structure in accordance with the following formula: wherein L is a member selected from substituted or unsubstituted purine, substituted or unsubstituted pyrimidine, substituted or unsubstituted pyridine and substituted or unsubstituted imidazole; Ml is a member selected from O and S; R40 and R41 are each members independently selected from H, aralkyl, substituted aralkyl, (CH2) sOH, C02H, C02 alkyl, C (0) NH2, C (O) NHalkyl, WITH (alkyl) 2, C (0) R23, OH, alkoxy, aryloxy, SH, S-alkyl, S-aryl, alkyl of S02, S03H, SCF3, CN, halogen, CF3, N02, (CH2) NR26R27, S02NH2, OCH2CH2NH2, OCH2CH2NHalkyl ?, OCH2CH2N (alkyl) 2, oxazolidin-2-yl, oxazolidin-2-yl substituted with alkyl, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl , substituted or unsubstituted heteroaryl, wherein R26 and R27 are independently selected from hydrogen, alkyl and alkanoyl; t is an integer selected from 0 to 2; s is an integer selected from 1 to 3; R42 is selected member of H, haloalkyl, aralkyl, substituted aralkyl, (CH2) r0H, OH, CH2NR26R27, C02H, C02 alkyl, CONH2, S-alkyl, S-aryl, S02 alkyl, S03H, SCF3, CN, halogen, CF3, N02, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl, wherein r is an integer selected from 1 to 6; and R43, R44 and R45 are each members independently selected from substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl. 88. The method of compliance with the claim 80, characterized in that the microorganism is an etiologic agent of onychomycosis. 89. The method according to claim 80, characterized in that the microorganism which is a member selected from a dermatophyte, Trichophyton spp., Microeporum spp., Epidermophyton spp. and yeast type mushrooms. 90. The method of compliance with the claim 89, characterized in that the microorganism is a member selected from Trichophyton species. 91. The method of compliance with the claim 90, characterized in that the microorganism is a member selected from T. rubrum and T. menagrophytes. 92. The method according to claim 79, characterized in that the compound inhibits post-transfer editing of a tRNA improperly loaded by the tRNA synthetase. 93. A method for killing a microorganism or inhibiting the growth of a microorganism, in a human or animal characterized by comprising contacting the microorganism with an effective pharmaceutical formulation to inhibit activity of an editing domain of a tRNA synthetase of the microorganism. 94. The method according to claim 93, characterized in that the pharmaceutical formulation comprises a member selected from cyclic boronic ester, cyclic borinic ester, 2'-amino ribofuranose portion and a 3'-amino ribofuranose portion. 95. The method according to claim 93, characterized in that the microorganism is a member selected from bacteria, fungi, yeast and parasites. 96. The method according to claim 95, characterized in that the fungus is a member selected from species of Candida, species of Trichophyton, species of Microeporium, species of Aspergillus, species of Cryptococcus, species of Blaetomycee, species of Cocciodiodee, species of Histoplasma, species of Paracoccidiode, species of Phycomycetee, species of Malaeeezia, species of Fuearium, species of Epidermophyton, species of Schytalidium, species of Scopulariopeie, species of Al ternarla, species of Penicillium, species of Phalophora, species of Rhizopue, species of Scedoepori um and kind of Zygomycetee. 97. The method according to claim 93, characterized in that the microorganism is an etiologic agent of onychomycosis. 98. The method according to claim 93, characterized in that the pharmaceutical formulation is present in a selected member of a dermatophyte, Trichophyton, Microsporum, Epidermophyton and yeast-type fungi. 99. The method of compliance with the claim 98, characterized in that the microorganism is a member selected from Trichophyton species. 100. The method according to the claim 99, characterized in that the microorganism is a selected member of T. rubrum and T. menagrophytee. 101. The method according to claim 93, characterized in that it has the condition that the pharmaceutical formulation does not comprise a structure according to the formula: wherein q is an integer selected from 1 to 5. 102. The method according to claim 93, characterized in that the pharmaceutical formulation comprises a member selected from a 2'-amino ribofuranose portion and a 3'-amino ribofuranose portion. 103. The method according to claim 102, characterized in that the 2'-amino ribofuranose portion has a structure according to the following formula: and the 3'-amino-ribofuranose portion has a structure in accordance with the following formula: wherein L is a member selected from substituted or unsubstituted purine, substituted or unsubstituted pyrimidine, substituted or unsubstituted pyridine and substituted or unsubstituted imidazole; Ml is a member selected from O and S; R40 and R41 are each members independently selected from H, aralkyl, substituted aralkyl, (CH2) sOH, C02H, C02 alkyl, C (0) NH2, C (O) NHalkyl, CON (alkyl) 2, C (0) R23, OH, alkoxy, aryloxy, SH, S-alkyl, S-aryl, alkyl of S02, S03H, SCF3, CN, halogen, CF3, N02, (CH2) NR26R27, S02NH2, OCH2CH2NH2, OCH2CH2NHalkyl, OCH2CH2N (alkyl) 2, oxazolidin-2-yl, oxazolidin-2-yl substituted with alkyl, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, substituted heteroaryl or not replaced, wherein R26 and R27 are independently selected from hydrogen, alkyl and alkanoyl; t is an integer selected from 0 to 2; s is an integer selected from 1 to 3; R42 is selected member of H, haloalkyl, aralkyl, substituted aralkyl, (CH2) r0H, OH, CH2NR26R27, C02H, C02 alkyl, C0NH2, S-alkyl, S-aryl, S02 alkyl, S03H, SCF3, CN, halogen , CF3, N02, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl, wherein r is an integer selected from 1 to 6; and R43, R44 and R45 are each members independently selected from substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl. 104. The method according to claim 94, characterized in that the cyclic boronic ester is 1,3-dihydro-5-f luoro-1-hydroxy-2, 1-benzoxazole. 105. Use of an effective pharmaceutical formulation for inhibiting activity of a tRNA synthetase editing domain of the microorganism, for the manufacture of a medicament for treating or preventing an infection by a microorganism in a human or animal. 106. Use according to claim 105, wherein the pharmaceutical formulation comprises a member selected from cyclic boronic ester, cyclic borinic ester, 2'-amino ribofuranose portion and a 3'-amino ribofuranose portion. 107. Use according to claim 105, wherein the microorganism is a selected member of bacteria, fungi, yeast and parasites. 108. Use according to claim 105, wherein the tRNA synthetase is a selected member of mitochondrial tRNA synthetase and cytoplasmic tRNA synthetase. 109. Use according to claim 108, wherein the tRNA synthetase is a member selected from alanyl tRNA synthetase, isoleucyl tRNA synthetase, leucyl tRNA synthetase, methionyl tRNA synthetase, lysyl tRNA synthetase, phenylalanyl tRNA synthetase, prolyl tRNA synthetase, threonyl tRNA synthetase and valil tRNA synthetase. 110. Use in accordance with the claim 105, wherein the compound has a KD, synthesis of more than 100 μM against a synthetic domain of the tRNA synthetase. 111. Use according to claim 110, wherein the ratio of a minimum concentration of the compound that inhibits the editing domain to a minimum concentration of the compound that inhibits the synthetic domain of the tRNA synthetase, represented as KD, edition / D, synthesis / is less than one. 112. Use according to claim 111, wherein the KD / edition / KD, synthesis of the compound is a selected member of less than 0.5, less than 0.1 and less than 0.05. 113. Use according to claim 105, wherein it has the proviso that the pharmaceutical formulation does not comprise a structure according to the formula: wherein q is an integer selected from 1 to 5. 114. Use according to claim 106, wherein the pharmaceutical formulation comprises a member selected from a 2'-amino ribofuranose portion and a 3 'amino ribofuranose portion. 115. Use according to claim 114, wherein the 2'-amino ribofuranose portion and the 2'-amino ribofuranose portion have a structure in accordance with the following formula: and the 3'-amino-ribofuranose portion has a structure in accordance with the following formula: wherein L is a member selected from substituted or unsubstituted purine, substituted or unsubstituted pyrimidine, substituted or unsubstituted pyridine and substituted or unsubstituted imidazole; Ml is a member selected from 0 and S; R40 and R41 are each members independently selected from H, aralkyl, substituted aralkyl, (CH2) s0H, C02H, C02 alkyl, C (0) NH2, C (O) NHalkyl, CON (alkyl) 2, C (0) R23, OH, alkoxy, aryloxy, SH, S-alkyl , S-aryl, S02 alkyl, S03H, SCF3, CN, halogen, CF3, N02, (CH2) NR26R27, S02NH2, 0CH2CH2NH2, 0CH2CH2NHalkyl, 0CH2CH2N (alkyl) 2, oxazolidin-2-yl, oxazolidin-2-yl substituted with alkyl, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, wherein R26 and R27 are independently selected from hydrogen, alkyl and alkanoyl; t is an integer selected from 0 to 2; s is an integer selected from 1 to 3; R42 is selected member of H, haloalkyl, aralkyl, substituted aralkyl, (CH2) r0H, OH, CH2NR26R27, CC ^ H, CC ^ alkyl, C0NH2, S-alkyl, S-aryl, SC ^ alkyl, SC ^ H , SCF3, CN, halogen, CF3, NC ^, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl, wherein r is an integer selected from 1 to 6; and R43, R44 and R45 are each members independently selected from substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl. 116. Use according to claim 115, wherein the pharmaceutical formulation comprises a 2'-amino ribofuranose portion and the 2'-amino-ribofuranose portion has a structure according to the following formula: 117. Use according to claim 106, wherein the cyclic boronic ester is 1,3-dihydro-5-fluoro-l-hydroxy-2, 1-benzoxazole. 118. Use according to claim 105, wherein the infection is a selected member of a systemic infection, an ungular infection, a periungular infection, a subungual infection and a cutaneous infection. 119. Use according to claim 105, wherein the infection is onychomycosis. 120. Use according to claim 105, wherein the infection is a selected member of chloronychia, paronychias, erysipeloid, onychorhexis, gonorrhea, swimming pool granuloma, larva migrans, leprosy, Orf nodule, dairy nodules, herpetic whitlow, bacterial perionixis. acute, chronic perionixis, sporotrichosis, syphilis, warty skin due to tuberculosis, tularemia, tungiasis, peri-subungual warts, area, nail dystrophy (trachyochia), dermatological diseases, psoriasis, pustular psoriasis, alopecia aerata, pustular parakeratosis, contact dermatosis, Reiter's syndrome, acral psoriasiform dermatitis, lichen planus, idiopathic atrophy in the nails, clear lichen, striated lichen, linear warty epidermal nevus inflammatory (I VEN), alopecia, pemphigus, pemphigus bullosa, acquired bullous epidermolysis, Darier's disease, pityriasis rubra pilaris, palmoplantar keratoderma, contact eczema, polymorphic erythema, sama, Bazex syndrome, systemic scleroderma, systemic lupus erythematosus, lupus erythematosus chronic, dermatomyositis, sporotrichosis, mycotic keratitis, oculomicosis by extension, endogenous oculomicosis, lobomycosis, mycetoma, stone, pityriasis versicolor, Tinea corporie, Tinea crurie, Tinea pedie, Tinea barbae, Tinea capi tie, Tinea nigra, otomycosis, tinea favoea, cromomycosis , and Tinea imbricata. 121. A unit dose formulation of an amount of an effective compound characterized in that it is to inhibit conversion of tRNA molecule to a tRNA molecule loaded by a microorganism to inhibit an editing domain of a tRNA synthetase. 122. The formulation according to claim 121, characterized in that it further comprises a pharmaceutically acceptable excipient. 123. The formulation according to claim 121, characterized in that the cell is a microbial cell. 124. The formulation according to claim 121, characterized in that the microorganism is a selected member of bacteria, fungi, yeast and parasites. 125. The formulation according to claim 121, characterized in that the tRNA synthetase is a member selected from mitochondrial tRNA synthetase and a cytoplasmic tRNA synthetase. 126. The formulation according to claim 125, characterized in that the tRNA synthetase is a member selected from alanyl tRNA synthetase, isoleucyl tRNA synthetase, leucyl tRNA synthetase, methionyl tRNA synthetase, lysyl tRNA synthetase, phenylalanyl tRNA synthetase, prolyl tRNA synthetase, threonyl tRNA synthetase and valyl tRNA synthetase. 127. The formulation according to claim 121, characterized in that the compound has a KD, synthesis of more than 100 μM against a synthetic domain of the tRNA synthetase. 128. The formulation according to claim 127, characterized in that the ratio of a minimum concentration of the compound that inhibits the editing domain to a minimum concentration of the compound that inhibits the synthetic domain of the tRNA synthetase, represented as KD; edíción / KD, synthesis / is less than one. 129. The formulation according to claim 128, characterized in that the KD, edition / KD, synthesis of the compound is a selected member of less than 0.5, less than 0.1 and less than 0.05. 130. The formulation according to claim 121, characterized in that the pharmaceutical formulation comprises a member selected from cyclic boronic ester, cyclic borinic ester, 2'-amino ribofuranose portion and a 3'-amino ribofuranose portion. 131. The method according to claim 130, characterized in that the 2'-amino ribofuranose portion has a structure according to the following formula: and the 3'-amino-ribofuranose portion has a structure in accordance with the following formula: wherein L is a member selected from substituted or unsubstituted purine, substituted or unsubstituted pyrimidine, substituted or unsubstituted pyridine and substituted or unsubstituted imidazole; Ml is a member selected from O and S; R40 and R41 are each members independently selected from H, aralkyl, substituted aralkyl, (CH2) sOH, C02H, C02 alkyl, C (0) NH2, C (O) NHalkyl, CON (alkyl) 2, C (0) R23, OH, alkoxy, aryloxy, SH, S-alkyl, S-aryl, alkyl of S02, S03H, SCF3, CN, halogen, CF3, N02, (CH2) NR26R27, S02NH2, 0CH2CH2NH2, 0CH2CH2NHalkyl, 0CH2CH2N (alkyl) 2, oxazolidin-2-yl, oxazolidin-2-yl substituted with alkyl, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, substituted heteroaryl or not replaced, wherein R26 and R27 are independently selected from hydrogen, alkyl and alkanoyl; t is an integer selected from 0 to 2; s is an integer selected from 1 to 3; R42 is selected member of H, haloalkyl, aralkyl, substituted aralkyl, (CH2) r0H, OH, CH2NR26R27, C02H, C02 alkyl, CONH2, S-alkyl, S-aryl, S02 alkyl, SO3H, SCF3, CN, halogen, CF3, N02, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl, wherein r is an integer selected from 1 to 6; and R43, R44 and R45 are each members independently selected from substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl. 132. The formulation according to claim 131, characterized in that it has the proviso that the pharmaceutical formulation does not comprise a structure according to the formula: 133. The formulation according to claim 130, characterized in that the cyclic boronic ester is 1,3-dihydro-5-fluoro-l-hydroxy-2, 1-benzoxazole. 134. The formulation according to claim 121, characterized in that the cell is a cell of an etiologic agent of onychomycosis. 135. The formulation according to claim 121, characterized in that the cell is a selected member of Trychophyton species. 136. The formulation according to claim 121, characterized in that the compound has a KD, synthesis of more than 100 μM against a synthetic domain of the tRNA synthetase. 137. A method for identifying a compound that binds to an editing domain of a tRNA synthetase, characterized in that it comprises: a) contacting the editing domain with a test compound under conditions suitable for binding; and b) detecting the binding of the test compound to the editing domain. 138. The method according to claim 137, characterized in that detecting the binding of the compound comprises using at least one detectable element, isotope or chemical label attached to the compound. 139. The method according to claim 138, characterized in that the element, isotope or chemical marker is detected by a fluorescent, luminescent, radioactive or absorbance reading. 140. The method according to claim 137, characterized in that contacting the test compound with the editing domain also includes contacting in addition the test compound and the editing domain with a member selected from AMP and a molecule with a terminal adenosine. 141. The method according to claim 137, characterized in that the tRNA synthetase is derived from a member selected from alanyl tRNA synthetase, isoleucyl tRNA synthetase, leucyl tRNA synthetase, methionyl tRNA synthetase, lysyl tRNA synthetase, phenylalanyl tRNA synthetase, prolyl tRNA synthetase , threonyl tRNA synthetase and valil tRNA synthetase. 142. The method according to claim 141, characterized in that the tRNA synthetase is derived from leucyl tRNA synthetase. 143. The method according to claim 141, characterized in that the tRNA synthetase is derived from a mutated tRNA synthetase, wherein the mutated tRNA synthetase comprises amino acid mutations in an editing domain. 144. The method according to claim 143, characterized in that the mutated tRNA synthetase comprises amino acid mutations in the editing domain as listed in Table 4. 145. The method according to claim 137, characterized in that the domain of One tRNA synthetase edition comprises the amino acid sequence of SEQ ID NOS: 1-15. 146. A method for identifying a compound that binds to an editing domain of a tRNA synthetase, the assay characterized in that it comprises: a) contacting the editing domain of a tRNA synthetase with the compound under conditions suitable for binding of the tRNA synthetase. compound to the editing domain of a tRNA synthetase; b) comparing a biological activity of the tRNA synthetase editing domain that contacts the compound with biological activity when no contact is made with the compound; c) identifying the compound as binding to the editing domain of a tRNA synthetase if the biological activity of the editing domain of a tRNA synthetase is reduced when it makes contact with the compound. 147. The method according to claim 146, characterized in that the biological activity is hydrolysis of non-cognate amino acid. 148. The method according to claim 147, characterized in that the hydrolysis of the non-cognate amino acid is detected through the use of one or more markers. 149. The method according to claim 148, characterized in that the labels include a radioactive label, a fluorescent label, an antibody or a combination thereof. 150. The method according to claim 148, characterized in that the markers can be detected using spectroscopy. 151. The method according to claim 146, characterized in that the editing domain of a tRNA synthetase is derived from a member selected from alanyl tRNA synthetase, isoleucyl tRNA synthetase, leucyl tRNA synthetase, methionyl tRNA synthetase, lysyl tRNA synthetase, phenylalanyl tRNA. synthetase, prolyl tRNA synthetase, threonyl tRNA synthetase and valil tRNA synthetase. 152. The method according to claim 151, characterized in that the editing domain of a tRNA synthetase is derived from leucyl tRNA synthetase. 153. A method for generating tRNA molecules with a non-cognate amino acid, characterized by comprising: a) creating or isolating a mutated tRNA synthetase with altered amino acid editing domains; and b) contacting a tRNA molecule with the mutated tRNA synthetase and a non-cognate amino acid. 154. The method according to claim 153, characterized in that the mutated tRNA synthetase contains one or more amino acid mutations in an editing domain. 155. The method according to claim 153, characterized in that the mutated tRNA synthetase is incapable of binding to 1,3-dihydro-5-fluoro-l-hydroxy-2, 1-benzoxazole. 156. The method according to claim 153, characterized in that the mutated tRNA synthetase is capable of binding to 1,3-dihydro-5-fluoro-l-hydroxy-2, 1-benzoxazole. 157. A composition comprising one or more tRNA molecules linked to non-cognate amino acids, characterized in that the tRNA molecules are synthesized using one or more mutated tRNA synthetases isolated to a microorganism or a cell line derived from a microorganism. 158. The composition according to claim 157, characterized in that the microorganism is a fungus or a yeast. 159. The composition according to claim 157, characterized in that the mutated tRNA synthetases contain amino acid mutations in their editing domains. 160. The composition according to claim 157, characterized in that the mutated tRNA synthetases comprise point mutations in the editing domain as listed in table 4. 161. A method for making a boronic ester containing tetrahydropyran, the ester has a structure according to the following formula: wherein R1 and R2 are members independently selected from H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl; wherein R1 and R2, together with the atoms to which they are attached, can optionally be joined to form a 4 to 7 membered ring; R9a, R10a, Rlla and R12a are members independently selected from H, OR *, NR * R **, SR *, -S (0) R *, -S (0) 2R *, -S (0) 2NR * R **, nitro, halogen, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted heteroaryl or not replaced; wherein R * and R ** is a member selected from H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl; characterized in that it comprises: a) subjecting a first compound to conditions of Grignard or organolithium, the first compound has a structure according to the following formula: b) contacting the product of step a) with a borate ester, thereby forming the boronic ester containing tetrahydropyran 162. The method according to claim 161, characterized in that the halogen is a member selected from iodine and bromine. 163. The method according to claim 161, characterized in that the borate ester is a member selected from BfOR1) 2 (OR2), wherein R1 and R2 are each members independently selected from H, substituted or unsubstituted methyl, ethyl substituted or unsubstituted, substituted or unsubstituted propyl, unsubstituted or substituted isopropyl, substituted or unsubstituted butyl, substituted or unsubstituted t-butyl, substituted or unsubstituted phenyl, and unsubstituted or substituted benzyl; and wherein R1 and R2, together with the atoms to which they are attached, can optionally form a member selected from substituted or unsubstituted dioxaborolane, substituted or unsubstituted dioxaborin, and substituted or unsubstituted dioxaborepane. 164. The method of compliance with the claim 161, characterized in that the borate ester is a member selected from BOR1) 2 (OR2), wherein R1 and R2, together with the atoms to which they are attached, form a member selected from dioxaborolane, substituted or unsubstituted tetramethyldioxoborolane, phenyldioxaborolane substituted or not replaced, dioxaborin, dimethyldioxaborin and dioxaborepane. 165. The method according to claim 161, characterized in that the Grignard or organolithium conditions further comprise diisobutylaluminum hydride. 166. The method according to claim 161, characterized in that the temperature of the Grignard reaction does not exceed about 35 ° C. 167. The method according to claim 161, characterized in that step (b) is carried out at a temperature of about -30 ° C to about -20 ° C. 168. The method according to claim 161, characterized in that the boronic ester containing tetrahydropyran is 169. A method for making a compound having a structure according to the following formula characterized in that it comprises: a) subjecting a first compound to Grignard or organolithium conditions, the first compound having a structure according to the following formula: b) rapidly quench the reaction with water and an organic acid, thereby forming the compound. 170. The method according to claim 169, characterized in that the organic acid is a member selected from acetic acid. 171. The method according to claim 169, characterized in that the rapid cooling step essentially does not come into contact with a strong acid. 172. The method according to claim 169, characterized in that the 173. The method according to claim 169, characterized in that the compound is purified by recrystallization from a recrystallization solvent, wherein the recrystallization solvent essentially does not contain acetonitrile. 174. The method according to claim 173, characterized in that the recrystallization solvent contains toluene and heptane. 175. A compound characterized in that it has a structure that is a member selected from: where q is a number between 0 and 1; R9 is halogen; Ra, Rb, R °, Rd and Re are members selected independently from a selected member of H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl; with the proviso that the compound is not a selected member of 176. The compound according to claim 175, characterized in that the structure is a member selected from: 177. The compound according to claim 175 or 176, characterized in that Ra, Rd and Re are each members selected independently of: 178. The compound according to claim 175 or 176, characterized in that Rb and Rc are members independently selected from H, methyl, and wherein R and R are, together with the nitrogen to which they are attached, optionally attached to form a selected member of 179. The compound according to claim 175, characterized in that Rb is H and Rc is a member selected from H, methyl, 180. The compound according to claim 175, characterized in that Rb and Rc are optionally linked to form a member selected from 181. The compound according to claim 175, characterized in that Ra is a member selected from 182. The compound according to claim 175, characterized in that Rd is a member selected from 183. The compound according to claim 175, characterized in that Re is a member selected from 184. A compound characterized in that it has the structure that is a member selected from the following formulas OH H? .sl sT; & XX ° and-oAA 185. A pharmaceutical formulation characterized in that it comprises: a) a pharmaceutically acceptable excipient; b) the compound according to claim 184. 186. A pharmaceutical formulation characterized in that it comprises: a) a pharmaceutically acceptable excipient b) a compound that is a member selected from 187. A method for killing a microorganism or inhibiting the growth of a microorganism, characterized in that it comprises contacting the microorganism with a therapeutically effective amount of a compound according to claim 186. 188. A method for killing a microorganism or inhibiting the growth of a microorganism. a microorganism, characterized in that it comprises contacting the microorganism with a therapeutically effective amount of a pharmaceutical formulation in accordance with claim 185 or claim 186. 189. Use of the compound according to claim 184, for the manufacture of a drug to treat or prevent an infection in an animal. 190. Use of a pharmaceutical formulation according to claim 185 or claim 186, for the manufacture of a medicament for treating or preventing an infection in an animal. 191. A method characterized in that it is for manufacturing the compound according to claim 184. 192. A method characterized in that it is for manufacturing the pharmaceutical formulation according to claim 185 or claim 186.