MXPA06006218A

MXPA06006218A - Anti-inflammatory agents

Info

Publication number: MXPA06006218A
Application number: MXPA/A/2006/006218A
Authority: MX
Inventors: John Grainger David; John Fox David
Original assignee: Cambridge University Technical Services Limited; John Fox David; John Grainger David
Priority date: 2003-12-01
Filing date: 2006-06-01
Publication date: 2007-04-20

Abstract

The invention relates to the use of 3-aminocaprolactam derivatives for preparing a medicament intended to prevent or treat inflammatory disorders, and uses compounds of general formula (I) or a pharmaceutically acceptable salts thereof;wherein X is -CO-R1 or-SO2-R2, and R1 and R2 are carbonaceous substituents.

Description

ANTI-INFLAMMATORY AGENTS The invention relates to the use of 3-aminocaprolactam derivatives to prepare a medicament for the prevention or treatment of inflammatory disorders. Inflammation is an important component of a host's physiological defense. Increasingly, however, it is clear that temporary or spatially inappropriate inflammatory responses play a role in a wide range of diseases, including those with an obvious leukocyte component (such as autoimmune diseases, asthma or atherosclerosis), but also in diseases in which it has traditionally been considered that they do not involve leukocytes (such as osteoporosis or Alzheimer's disease). Chemokines are a large family of signaling molecules with homology for interleukin-8, which have been implicated in the regulation of leukocyte trafficking in both physiological and pathological conditions. With more than fifty ligands and twenty receptors involved in chemokine signaling, the system has the information density required to direct the leukocytes through complex immune regulatory processes of the bone marrow, towards the periphery, then back through the secondary lymphoid organs. However, this complexity of the chemokine system initially has hindered pharmacological approaches to modulate inflammatory responses by blocking the chemokine receptor. It has proved difficult to determine which receptor or chemokine receptors have to be inhibited to produce therapeutic benefit in a given inflammatory disease. More recently, a family of agents that block signaling in a broad range of chemokines has been described simultaneously: Reckless and co-authors, Biochem J. (1999) 340: 803-811. It was found that the first of such agents, a peptide called "Peptide 3", inhibits leukocyte migration induced by 5 different chemokines, while leaving migration unchanged in response to other chemoattractants (such as fMLP or TGF-beta). This peptide, and its analogues, such as NR58-3.14.3 (ie, sequence ID No. 1 c (DCys-DGIn-Dlie-DTrp-DLys-DGIn-DLys-DPro-DAsp-DLeu-DCys) -NH2 ), are collectively referred to as "Wide Spectrum Chemistry Inhibitors" (BSCI). Grainger and co-authors, Biochem. Pharm. 65 (2003) 1027-1034 have subsequently shown that BSCIs have potentially useful anti-inflammatory activity in a range of disease models in animals. Interestingly, simultaneous blockade of multiple chemokines is apparently not associated with acute or chronic toxicity, suggesting that this approach may be a useful strategy to develop new anti-inflammatory drugs with benefits similar to steroids, but with reduced side effects. . However, peptide and peptoid derivatives such as NR58-3.14.3 may not be optimal for in vivo use. They are quite expensive to synthesize, and have relatively unfavorable pharmacokinetic and pharmacodynamic properties. For example, NR58-3.14.3 is not orally bioavailable, and is removed from blood plasma with a half-life of less than 30 minutes after intravenous injection. Two parallel strategies have been adpotado to identify novel preparations that maintain the antiinflammatory properties of peptide 3 and NR58-3.14.3, but have improved characteristics for use as pharmaceutical substances. First, a series of peptide analogues has been developed, some of which have longer half-lives in plasma than NR58-3.14.3, and which are considerably cheaper to synthesize. Second, a detailed structure: A peptide activity analysis was carried out to identify key pharmacophores and design non-peptide structures that maintain the beneficial properties of the original peptide. This second approach produced several series of structurally distinct compounds, which maintained the anti-inflammatory properties of the peptides, including 16-amino and 16-aminoalkyl derivatives of the alkaloid yohimbine, as well as a range of N-substituted 3-aminoglutarimides. (Reference: Fox and co-authors, J Med Chem 45 (2002) 360-370: WO 99/12968 and WO 00/42071). All of these compounds are broad spectrum chemokine inhibitors, which maintain selectivity over non-chemokine chemoattractants, and a number of them have been shown to block acute inflammation in vivo. The most potent and selective of these compounds was (S) -3- (undec-IO-enoyl) -aminoglutarimide (NR58.4), which inhibited the chemokine-induced migration in vitro with an ED50 of 5 nM. However, additional studies revealed that the aminoglutarimide ring was susceptible to the enzyme ring opening in serum. Consequently, for some applications (for example, where inflammation under treatment is chronic, such as in autonomic diseases), these compounds may not have optimal properties, and a more stable compound with similar anti-inflammatory properties may be superior. As an approach to identify these stable analogs, various (S) -3- (undec-IO-enoyl) -aminoglutarimide derivatives have been tested for their stability in serum. One of these derivatives, the 6-deoxo analogue (SJ-3- (undec-10-enoyl) -tetrahydropyridin-2-one, is completely stable in human serum for at least 7 days at 37 ° C, but has considerably reduced potency. compared to the parent molecule The amide derivatives of 3-aminocaprolactam have already been described in the art, for example: - Japanese patent application No. 09087331 describes amide derivatives of 3-aminocaprolactam wherein the alkyl-amide side chain can contain from 2 to 30 carbon atoms These compounds have been presented as oil gelling agents.

U.S. Patent No. 6,395,282 describes immunogenic conjugates containing a carrier molecule coupled to an autoinducer of Gram-negative bacteria, wherein said autoinducer can be an amide derivative of 3-aminocaprolactam, wherein the alkyl-amide side chain can contain up to 34 carbon atoms. carbon. However, only one therapeutic use is described for the conjugates, and not for the isolated amide derivative. An article by Weiss and co-authors (Research Communications in Psychology, Psychiatry and Behavior (1992), 17 (3-4), 153-159) describes a series of amide derivatives of 3-aminocaprolactam, and among others 3-hexanamido- DL-ecaprolactam, and 3-dodecanamido-DL-ecaprolactam. These compounds are presented as having only an in vitro activity, but have no significant effect in vivo. In other words, although some alkyl-amide derivatives of 3-amidocaprolactam are certainly well known in the art, no real pharmaceutical use has been described for the 3-aminocaprolactam amide derivatives. The invention provides the use of a compound of the general formula (I), or a salt thereof acceptable for pharmaceutical use, for the preparation of a medicament directed to treat an inflammatory disorder: > wherein X is -CO-R1 or -SO2-R2, R is an alkyl, haloalkyl, alkoxy, haloalkoxy, alkenyl, alkynyl or alkylamino radical of 4 to 20 carbon atoms (eg from 5 to 20 carbon atoms, 8 to 20 carbon atoms, 9 to 20 carbon atoms, 10 to 18 carbon atoms, 12 to 18 carbon atoms, 13 to 18 carbon atoms, 13 to 17 carbon atoms); and R2 is an alkyl radical of 4 to 20 carbon atoms (for example 5 to 20 carbon atoms, 8 to 20 carbon atoms, 9 to 20 carbon atoms, 10 to 18 carbon atoms, 12 to 18 carbon atoms, 13 to 18 carbon atoms, 14 to 18 carbon atoms, and 13 to 17 carbon atoms). Alternatively, R1 and R2 may be independently selected from a peptide moiety, for example, with 1 to 4 peptide moieties linked together by peptide bonds (eg, a peptide moiety of 1 to 4 amino acid residues). The carbon atom in the 3-position of the caprolactam ring is asymmetric, and accordingly, the compounds according to the present invention have two possible enantiomeric forms, that is, the "R" and "S" configurations. The present invention comprises the two enantiomeric forms and all combinations of these forms, including the racemic mixtures "RS" With a view of simplicity, when a specific configuration is not shown in the structural formulas, it is to be understood that the two enantiomeric forms and their mixtures are represented. British priority applications 0327775.3 and 0417436.3 by the same applicant in 3-amino-caprolactam compounds have correctly indicated that compounds with "S" configuration are preferred. These requests incorrectly illustrate a general formula (I ') that shows the "R" configuration. Preferably, the compounds of the general formula (I) or their pharmaceutically acceptable salts used in accordance with this aspect of the invention will be compounds of the general formula (I ') . { P.}. where X has the same meaning defined above. The carbon atoms in R1 and R2 may be linear or branched. The compounds of the general formula (I) or (I '), or their pharmaceutically acceptable salts, can be such that the alkyl, haloalkyl, alkoxy, haloalkoxy, alkenyl, alkynyl or alkylamino part of the radical R1 can be linear or branched, but contains a linear chain of at least 8 or at least 10 carbon atoms. The invention also provides pharmaceutical compositions containing, as an active ingredient, a compound of the general formula (I), or a salt thereof acceptable for pharmaceutical use, and at least one excipient and / or carrier acceptable for pharmaceutical use: m wherein X is -CO-R1 or -SO2-R2, R1 is an alkyl, haloalkyl, alkoxy, haloalkoxy, alkenyl, alkynyl or alkylamino radical of 4 to 20 carbon atoms (eg from 5 to 20 carbon atoms, 8 to 20 carbon atoms, 9 to 20 carbon atoms, 10 to 18 carbon atoms, 12 to 18 carbon atoms, 13 to 18 carbon atoms, 14 to 18 carbon atoms, 13 to 17 carbon atoms); and R2 is an alkyl radical of 4 to 20 carbon atoms (for example 5 to 20 carbon atoms, 8 to 20 carbon atoms, 9 to 20 carbon atoms, 10 to 18 carbon atoms, 12 at 1 8 carbon atoms, 13 to 1 8 carbon atoms, 14 to 18 carbon atoms, and 13 to 17 carbon atoms). Alternatively, R1 and R2 can be independently selected from a peptide moiety, for example having 1 to 4 peptide moieties linked together with peptide bonds (for example a peptide moiety of 1 to 4 amino acid residues). Preferably, the compounds of the general formula (I) or their pharmaceutically acceptable salts used in accordance with this aspect of the invention will be compounds of the general formula (! ') () where X has the same meaning as described above. By "pharmaceutically acceptable salt" is meant, in particular, addition salts of inorganic acids such as hydrochloride, hydrobromide, hydroiodide, sulfate, phosphate, diphosphate and nitrate, or of organic acids such as acetate, maleate, fumarate, tartrate, succinate , citrate, lactate, methanesulfonate, p-toluenesulfonate, palmoate and stearate. The salts formed from bases such as sodium or potassium hydroxide are also within the scope of the present invention, when they can be used. For other examples of acceptable salts for pharmaceutical use, reference may be made to "Selection of salts for basic drugs", Int. J Pharm. (1986), 3, 201-217. The pharmaceutical composition may be in the form of a solid, for example powders, granules, tablets, gelatin capsules, liposomes or suppositories. Suitable solid supports can be, for example, calcium phosphate, magnesium stearate, talc, sugars, lactose, dextrin, starch, gelatin, cellulose, methylcellulose, sodium carboxymethylcellulose, polyvinylpyrrolidine and wax. Other excipients and / or carriers acceptable for pharmaceutical use, which are appropriate, will be familiar to those skilled in the art. The pharmaceutical compositions according to the invention can also be presented in liquid form, for example, solutions, emulsions, suspensions or syrups. Suitable liquid supports can be, for example, water, organic solvents such as glycerol or glycols, as well as their mixtures, in varying proportions, in water. The invention also provides compounds and salts thereof of the general formula (I) 0) wherein X is -CO-R1 or -SO2-R2, R1 is an alkyl, haloalkyl, alkoxy, haloalkoxy, alkenyl, alkynyl or alkylamino radical of 4 to 20 carbon atoms (for example from 5 to 20 carbon atoms) , from 8 to 20 carbon atoms, from 9 to 20 carbon atoms, from 10 to 18 carbon atoms, from 12 to 18 carbon atoms, from 13 to 18 carbon atoms, from 14 to 18 carbon atoms, from 13 to 17 carbon atoms); and R2 is an alkyl radical of 4 to 20 carbon atoms (for example 5 to 20 carbon atoms, 8 to 20 carbon atoms, 9 to 20 carbon atoms, 10 to 18 carbon atoms, 12 to 18 carbon atoms, 13 to 18 carbon atoms, 14 to 18 carbon atoms and 13 to 17 carbon atoms). Alternatively, R1 and R2 may be independently selected from a peptide moiety, for example having from 1 to 4 peptide moieties linked together by peptide bonds (for example a peptide moiety of 1 to 4 amino acid residues). Preferably, the compounds of the general formula (I) or their salts used according to this aspect of the invention, will be compounds of the general formula (! ') (P) where X has the same meaning as described above. Preferably, the compounds of the general formula (I) or (I ') when used in the invention, or their salts, will be such that the alkyl, haloalkyl, alkoxy, haloalkoxy, alkenyl, alkynyl, or alkylamino part of the radical R 1 is linear or branched, but contains a linear chain of at least 8 to 10 carbon atoms. In particular, the preferred compounds of the general formula (I) or (I ') and their salts according to any aspect of the present invention are selected from the group consisting of: SJ-3-hexadecanoylamino-caprolactam; -fSJ-3-undecanoylamino-caprolactam; - SJ-S-Ideodec-l-enoyl) amino-ca pro-lactam; -fS -S-Iundec-IO-inoi amino-caproiactam; - SJ-3-tetradecanoi lam i no-ca pro lactam; - RJ-3-hexadecanoylamino-caprolactam; -fSJ-3-octadecanoylamino-caprolactam; - SJ- (Z) -3- (hexadec-9-enel) amino-caprolactam; - (SJ- (Z) -3- (octadec-9-enoyl) amino-caprolactam; - RJ- (Z) -3- (octadec-9-enoyl) amino-caprolactam; - (, SJ-3- (2 ', 2, -dimethyl-dodecanoyl) amino-caprolactam; -fS -3- (decyloxycarbonyl) amino-caprolactam;-S) -C £) -3- (dodec-2-enoyl) amino-caprolactam; - SJ-3- (dec-9-enylaminocarbonyl) amino-caprolactam; - (S -S-idecylaminocarboni amino-caprolactam; and its salts. More preferred compounds will be selected from the group consisting of: fSJ-3-hexadecanoylamino-caprolactam (ie, the compound of the general formula (I ') wherein R 1 is hexadecanyl), (' S) -3- (2 ') , 2, -dimethyl-dodecanoyl) amino-caprolactam, (S -3- (2 ', 2'-dimethyl-propionyl) amino-caprolactam and its salts. As mentioned in the discussion of the prior art above, certain Alkylamide derivatives of 3-amino caprolactam can be known as compounds per se (although it is not currently known that any of them have been described as such, as pharmaceutical compositions or for medical use in an anti-inflammatory context). In the prior art description of straight chain alkylamide derivatives To the extent that any compound is known as such, it is not intended to claim this compound per se in this invention, and this is waived here, accordingly, the applicant explicitly distinguishes here among the derivatives of straight chain alkyl covered by the definition of formula (I) and (T) in this application, and the branched chain alkyl derivatives of formula (I) and (I1) of this application. The definition of R1 used herein, in connection with the compounds per se, may include all alkyl derivatives; alternatively, R1 may include all alkyl derivatives with the exception of certain specified straight chain alkyl derivatives; alternatively R1 may include all branched chain alkyl derivatives; and as a further alternative the definition of R1 can exclude all amide derivatives of 3-amino caprolactam. The invention includes compounds, compositions and uses thereof as defined, wherein the compound is in hydrated or solvated form. As indicated in the introduction, certain alkyl aminocaprolactam compounds per se, and compositions or conjugates containing them, may already be known in the prior art. The claim of any of these compounds or compositions known in the present invention is waived, either by specific waiver or by generic waiver of a class of compounds / compositions. The 3-aminocaprolactam amide derivatives described herein are functional BSCI. They are relatively inexpensive to synthesize, using synthetic synthesis routes provided here; they are stable in human serum and consequently have excellent pharmacokinetic properties; are available orally, have chemokine inhibitors with broad spectrum highly potent in vitro, with excellent selectivity on non-chemokine chemoattractants; there are highly potent and effective anti-inflammatory agents in vivo in models of inflammation in rodents; its administration is not associated with any significant acute toxicity in the doses necessary to achieve a maximum therapeutic effect. Taken together, these properties suggest that amide derivatives of 3-amino caprolactam represent anti-inflammatory drugs with advantages over the previously described compounds. In comparison with the prior art, the improvement of the present invention is based on the introduction of the aminocaprolactam portion. However, the chemical structure of the side chain (either alkylamide, alkylsulfonamide or peptide) can also significantly affect the properties of the molecule, such that the alkyl substituents with 2-position substitution (relative to carbonyl amide) or at position 1 (relative to the sulfonyl sulfonamide group) are significantly superior to those with linear alkyl chains (either alkyl amides or alkyl sulfonamides). Peptides of the prior art (such as NR58- 3.14.3) have the disadvantages that: (a) they are expensive and require solid phase synthesis (at least for the longer ones) and (b) they are eliminated very quickly by the Kidneys and (c) are generally less potent. The aminoglutarimides of the prior art are inexpensive, are not rapidly eliminated by the kidneys and are more potent, but have no metabolic stability. The improvement described here, the aminocaprolactams, are cheap, are not rapidly eliminated by the kidneys and are even more potent, and are also metabolically stable.

According to this invention, the inflammatory disorders which are intended to be prevented or treated by the compounds of the general formula (I) or (! ') Or their pharmaceutically acceptable salts or pharmaceutical compositions or medicaments containing them as active ingredients, include especially: - autoimmune diseases, for example such as multiple sclerosis; vascular disorders including stroke, coronary artery disease, myocardial infarction, unstable angina pectoris, atherosclerosis or vasculitis, eg Behget's syndrome, giant cell arteritis, polymyalgia rheumatica, Wegener's granulomatosis, Churg-Strauss syndrome vasculitis, purpura of Henoch-Schonlein and Kawasaki disease; - infection or viral reproduction, for example infections due to or replication of viruses including smallpox virus, herpes virus (eg, Herpesvirus samiri) cytomegalovirus (CMV) or lentivirus; - asthma; - osteoporosis; (low mineral density in the bones); - tumor growth; - rheumatoid arthritis; - rejection of organ transplantation and / or delayed function of graft or organ, for example, in patients with renal transplantation; - a disorder characterized by a high level of TNF-a; - psoriasis; - skin wounds; - disorders caused by intracellular parasites such as malaria or tuberculosis; - allergies; or - Alzheimer's disease. In accordance with this invention, additional inflammatory disorders include: ALS; - fibrosis (particularly pulmonary fibrosis, but not limited to fibrosis in the lung); - the formation of adhesions (particularly in the peritoneum and the pelvic region). - antigen-induced rejection response - suppression of immune response These clinical indications fall into the general definition of inflammatory disorders or disorders characterized by elevated levels of TNF-a. Where legally permissible, the invention also provides a method of treating, improving or prophylaxis of the symptoms of an inflammatory disease (including an adverse inflammatory reaction to any agent), by administering to a patient an amount of a compound , composition or anti-inflammatory drug, as claimed herein. The administration of a medicament according to the invention can be carried out topically, orally, parenterally, by intramuscular injection, etc. The expected administration dose for a medicament according to the invention is between 0.1 mg and 10 g, depending on the type of active compound used. According to the invention, the compounds of the general formula (I) or (! ') Can be prepared using the processes described hereinafter.

PREPARATION OF THE COMPOUNDS OF THE GENERAL FORMULA M > O fl ') All compounds of the general formula (I) or (I ') can be easily prepared according to general familiar methods to the person skilled in the art. However, the following preferred synthetic routes are proposed: (I) (i) DIAGRAM 1 According to the routes shown in Diagram 1: 3-Amino-caprolactam is treated with an acid chloride of the general formula R 1 -CO-CI, wherein R 1 is an alkyl, haloalkyl, alkenyl or alkynyl radical to produce the compounds of the general formula (I) wherein X is -CO-R1 and R1 is an alkyl, haloalkyl, alkenyl or alkynyl radical; or - The 3-amino-caprolactam is treated with an isocyanate of the general formula R'-NCO, wherein R 'is alkyl to produce the compounds of the general formula (I), wherein X is -CO-R1 and R1 is alkyl to produce the compounds of the general formula (I), wherein X is -COR1 and R1 is an alkylamino radical; - The 3-amino-caprolactam is treated with a sulfochloride of the general formula R2-CO2CI, wherein R2 is alkyl, to produce the compounds of the general formula (I), wherein X is -SO2-R2 and R2 is a alkyl radical; or - 3-Amino-caproactam is treated with a chloroformate of the general formula R'-O-CO-CI, wherein R 'is alkyl to produce the compounds of the general formula (I), wherein X is -CO-R1, and R1 is an alkoxy radical. The reactions shown in Diagram 1 can be carried out, for example, in chloroform or in dichloromethane. The most preferred solvent for the reaction is dichloromethane. The above reactions are preferably carried out in the presence of a base, for example Na 2 CO 3. All the above reactions can be carried out at room temperature (about 25 ° C) or more generally at a temperature between 20 and 50 ° C.

DEFINITIONS The term "approximately" refers to a range around the considered value. As used in this patent application, "about X" means a range from X minus 10% X to X plus 10% X, and preferably a range from X minus 5% X to X plus 5% X The use of a numerical scale in this description is intended to unambiguously include within the scope of the invention, all individual integers within the range, and all combinations of upper and lower limit numbers within the widest scope of the given range. . Therefore, for example, the range of 4 to 20 carbon atoms specified with respect to formula I (among others) is intended to include all integers between 4 and 20 and all sub-ranges of each combination of upper and lower numbers , whether or not they are explicitly exemplified. As used herein, the term "contains" must be read with the meanings of comprises and is constituted by. Accordingly, wherein the invention relates to a "pharmaceutical composition containing an active ingredient" as a compound, this terminology is intended to cover both compositions in which other active ingredients may be present and also compositions consisting solely of an active ingredient such as it defines. As used herein, the term "peptide portions" is intended to include the following 20 proteogénic amino acid residues of natural origin: It is also envisioned that modified and unusual amino acid residues, as well as peptide mimetics, fall within the definition of "peptide portions". Unless otherwise defined, all the technical and scientific terms used here have the same meaning that is usually understood by an ordinary specialist in the field to which the invention pertains. Similarly, all publications, patent applications, all patents and all other references mentioned herein are incorporated by reference (when legally permissible). The following examples are presented for the purpose of illustrating the above procedures, and should not be considered as limiting the scope of the invention.

FIGURES Figure 1 provides a comparison of (R) - and (S) - enantiomers of amino-caprolactam amide derivatives as migration inhibitors induced by MCP-1.

EXAMPLES GENERAL PROCEDURE FOR THE SYNTHESIS OF INITIAL COMPOUNDS The hydrochlorides of (R) and S-3-amino-caprolactam, and the hydro-pyrrolidine-5-carboxylates of (R, R) and (S, S) -3-amino-caprolactam, were synthesized according to the literature (see Boile and co-authors, J. Org. Chem. (1979), 44, 481-4847; Rezler and co-authors, J. Med. Chem. (1997), 40, 3508-3515).

EXAMPLE 1: ÍS) -3-HEXADECANOILAMINO-CAPRQLACTAMA: Hydrochloride of (SJ-3-amino-caprolactam (5 mmol) and Na2CO3 (15 mmol) in water (25 mL) was added to a solution of hexadecanoyl chloride (5 mmol) in dichloromethane (25 mL) at room temperature and The reaction mixture was stirred for 2 hours, then the organic layer was separated and the aqueous phase was extracted with additional dichloromethane (2 x 25 mL) The combined organic layers were dried over Na2CO3 and reduced in vacuo. by recrystallization from EtOAc, to give the titled compound (1.41 g, 77%) Melting point: 99-100 ° CM (c = 1, CHCl3) = +32.0 IR: vmax (cpT1): 3325, 3272 (NH), 1666, 1655, 1631 (CO), 1524 (NH) NMR with 1H (dH, 500 MHz, CDCl 3): 6.88 1H, d, J5.5, CHNH), 6.72 (1H, br s, CH2NW), 4.49 (1H, ddd, J 11, 6, 1, CtfNH), 3.29-3.16 (2H, m, CH2NH), 2.17 (2H, t, J 7.5, CH2CONH), 2.03 (1H, br d, J 13. 5, CH ring), 1.98-1. 89 (1H, m, CH ring), 1.85-1. 73 (2H, m, CH ring), 1.58 (2H, br qn J 7.0, CW2CH2CONH), 1.43 (1H, br qd, J 14, 3, CH ring), 1.38-1. 29 1H, br m, CH ring), 1.29-1.14 (24H, m, (CH2) 12) and 0.83 (3H, t, J6.5, CH3). NMR with 13 C (dc, 125 MHz, CDCl 3): 175.9, 172.3 (CO), 52.0 (NHCHCO), 42.1 (NCH2), 36.6, 31.9, 31.7, 29.6 (x6), 29.4, 29.3 (x2), 29.2, 28.8 , 27.9, 25.6, 22.6 (CH2) and 14.1 (CH3). m / z (C22H42N2O2Na): 389.31450 (calculated: 389.3144).

EXAMPLE 2: ÍS) -3-UNDECANOILAMINO-CAPROLACTAMA The fSJ-3-amino-caprolactam hydrochloride (2 mmol) and Na2CO3 (6 mmol) in water (25 mL) were added to a solution of undecanoyl chloride (2 mmol) in dichloromethane (25 mL) at room temperature and stirred the reaction mixture for 2 hours. The organic layer was then separated and the aqueous phase was extracted with additional dichloromethane (2 x 25 mL). The combined organic layers were dried over Na2CO3 and reduced in vacuo. The residue was urified by recrystallization from EtOAc to give the titled compound (397 mg, 67%). Melting point: 91-92 ° C. M (c = 1, CHCI3) = +30.2. IR: vmax (cm-1): 3342, 3313 (NH), 1676, 1638 (CO), 1519 (NH); 3342, 3292 (NH), 1671, 1639 (CO), 1513 (NH). RM with 1H (dH, 500 MHz, d6-DMSO): 7.76 (1H, t, J6, CH2NH), 7.68 (1H, d, J7, CHNH), 4.38 (1H, dd, J 10, 7, CHNH), 3.15 (1H, ddd, J 15. 5.11, 5, CHHNH), 3.04 (1H, dt, J 13, 6, CHHNH), 2.19-2.06 (2H, m, CH2CONH), 1.85 (1H, dt, J 10.5, 3, C-5 H), 1.77-1.68 (2H, m, C-4 H, C-6 H), 1.60 (1H, qt, J 12.3.5, C-5 H), 1.46 (2H, br qn J 6.5, CH2CH2CONH), 1.35 (1H, qd, J 12. 5.3, C-4 H), 1.31-1.13 (15H, m, (CH2) 7 + C-6H) and 0.85 (3H, t , 7.0, CH3). 13 C NMR (dc, 125 MHz, d6-DMSO): 174.4 (CO-ring), 171.3 (CO-chain), 51.3 (NHCHCO), 40.7 (NCH2), 35.2, 31.4, 31.3, 29.1, 29.0 (x2) , 28.9, 28. 8.28. 7, 27.8, 25.4, 22.2 (CH2) and 14.0 (CH3). m / z (C | 7H32N2O2Na): 319.23540 (calculated: 319.2361).

EXAMPLE 3: (S) -3- (UNDEC-10-ENOIL) AMINO-CAPROLACTAMA FSJ-3-amino-caprolactam hydrochloride (2 mmol) and Na2CO3 (6 mmol) in water (25 mL) were added to a solution of undec-10-enoyl chloride (2 mmol) in dichloromethane (25 mL) at room temperature environment, and the reaction mixture was stirred for 2 hours. The organic layer was then separated and the aqueous phase was extracted with additional dichloromethane (2 x 25 mL). The combined organic layers were dried over Na2CO3 and reduced in vacuo. The residue was purified by recrystallization from EtOAc to give the titled compound (423 mg, 72%). Melting point: 83-84 ° C. [«]? (c = 1, CHCI3) = +40.1. IR: Vmax (cm'1): 3327.3273 (NH), 1655.1630 (CO), 1521 (NH). NMR with 1H (dH, 500 MHz, d6-DMSO): 7.75 (1H, t, J6, CH2NH), 7.66 (1H, d, J7, CHNH), 5.76 (1H, ddt, J 17.10, 6.5 CH2 = CH), 4. 96 (1H, dq, J 17.2, CHH = CH, 4.96 (1H, ddt, J 17.2, 1, CHH = CH), 4. 36 (1H, dd, J 10, 7, CHNH), 3.14 (1H, ddd, J 15.5, 11.5, 5, CHHNH), 3.03 (1H, br dt, J 13, 5.5, CHHNH), 2.16-2. 06 (2H, m, CH2CONH), 1.98 (2H, br q, J7, CH2 = CHCH2), 1.85 (1H, dt, J 10.5, 3, C-5 H), 1.75-1.67 (2H, m, C- 4H, C-6H), 1.60 (1H, qt, J 13, 3.5, C-5 H), 1.44 (2H, br qn, J7, CH2CH2CONH), 1.39-1.27 (3H, m, CH2 = CHCH2CH2 + C- 4 H) and 1.31-1.13 (9H, m, (CH2) 4 + C-6 H). NMR with 13 C (dc, 125 MHz, d6-DMSO): 174.4 (CO-ring), 171.3 (CO-chain), 138.9 (CH2 = CH), 114.7 (CH2 = CH), 51.3 (NHCHCO), 40.7 (NCH2 ), 35.3, 33.3, 31.3, 29.0, 28.9 (x2) 28.7, 28.6, 28.4, 27.8 and 25.4 (CH2). m / z (C17H30N2O2Na): 317.21970 (Calculated: 317.2205).

EXAMPLE 4: fS) -3- (UNDEC-10-INOlL) AMINO-CAPROLACTAMA SJ-S-amino-caprolactam hydrochloride hydrochloride (2 mmol) and Na2CO3 (6 mmol) in water (25 mL) were added to a solution of undec-10-yl chloride (2 mmol) in dichloromethane (25 mL) at room temperature and the reaction mixture was stirred for 2 hours. The organic layer was then separated and the aqueous phase was extracted with additional dichloromethane (2x 25 mL). The combined organic layers were dried over Na2CO3 and reduced in vacuo. The residue was purified by recrystallization from EtOAc to give the titled compound (362 mg, 62%). Melting point: 73-75 ° C. afí (C = 1, CHCI3) = +42.1. IR: vmax (cm-1): 3332.3295 (NH), 1667, 1633 (CO), 1523 (NH).

NMR with 1H (dH, 500 MHz, d6-DMSO): 7.76 (1H, t, J 5.5, CH2NH), 7.68 (1H, d, J7, CHNH), 4.36 (1H, dd, J11, 7, CHNH), 3.16 (1H, ddd, J 15.5, 11.5, 5, CHHNH), 3.03 (1H, br dt, J 14, 7, CHHNH), 2.17-2.07 (4H, m, CH2CONH + CH2CCH), 1.85 (1H, m, C-5 H), 1.77-1.67 (2H, m, C-4 H, C-6 H), 1.62 (1H, br qt, J 13, 3.0, C-5 H), 1.50- 1.28 (5H, m , CH2CH2CONH + HCCCH2CH2 + C-4 H) and 1.28-1.13 (9H, m, (CH2) 4 + C-6 H). 13 C NMR (dc, 125 MHz, d 6 -DMSO): 174.4 (CO-ring), 171.3 (CO-chain), 84.6 (CH 2 CH), 71.1 (CH 2 CH), 51.3 (NHCHCO), 40.7 (NCH 2), 35.2, 31.3, 29.0, 28.8, 28.7, 28.5, 28.2, 28.0, 27.8, 25.4 and 17.8 (CH2). m / z (C | 7H28N2O2Na): 317.20470 (Calculated: 315.2048).

EXAMPLE 5: ÍS) -3-DODECANOILAMINO-CAPROLACTAMA Hydrochloride of (SJ-3-amino-caprolactam (2 mmol) and Na2CO3 (6 mmol) in water (25 mL) was added to a solution of dodecanoyl chloride (2 mmol) in dichloromethane (25 mL) at room temperature and The reaction mixture was stirred for 2 hours, then the organic layer was separated and the aqueous phase was extracted with additional dichloromethane (2 x 25 mL) The combined organic layers were dried over Na2CO3 and reduced in vacuo. by recrystallization from EtOAc to give the titled compound (439 mg, 71%). Melting point: 93-94 ° C. [«1» (c = 1, CHCI3) = +35.5. IR: vmax (cm "1): 3324, 3267 (NH), 1666, 1630 (CO), 1521 (NH). NMR with 1H (dH, 500 MHz, d6-DMSO): 7.76 (1H, br s, CH2NH ), 7.67 (1H, d, 7.CHNH), 4.38 (1H, dd, J 10.5, 7.5, CHNH), 3.15 (1H, ddd, J 15.5, 11.5, 5, CHHNH), 3.05 (1H, dt, J 14.5, 5.5, CHHNH), 2.17-2.07 (2H, m, CH2CONH), 1.90-1.80 (1H, m, C-5 H), 1.77-1.68 (2H, m, C-4 H, C-6 H) , 1.62 (1H, br qt, J 12.3 5, C- 5 H), 1.46 (2H, br qn J 6. 0, CH2CH2CONH), 1.36 (1H, qd, J 12.5, 2.5, C-4 H ), 1.31-1.13 (17H, m, (CH2) 8 + C-6 H) and 0.85 (3H, t, J 6.5, CH3). 13 C NMR (dc, 125 MHz, d6-DMSO): 174.4 (CO -anillo), 171.2 (CO-chain), 51.3 (NHCHCO), 40.7 (NCH2), 35.3, 31.4, 31.3, 29.1 (x3), 29.0 (x2), 28.8, 28.7, 27.8, 25.4, 22.2 (CH2) and 14.0 (CH3) .m / z (C18H34N2O2Na): 333.25150 (Calculated: 333.2518).

EXAMPLE 6: fS) -3-TETRADECANOILAMINO-CAPROLACTAMA Hydrochloride of ('SJ-3-amino-caproactam (2 mmol) and Na2CO3 (6 mmol) in water (25 mL) was added to a solution of tetradecanoyl chloride (2 mmol) in dichloromethane (25 mL) at room temperature and The reaction mixture was stirred for 2 hours, then the organic layer was separated and the aqueous phase was extracted with additional dichloromethane (2 x 25 mL) The combined organic layers were dried over Na2CO3 and reduced in vacuo. residue by recrystallization from EtOAc to give the titled compound (412 mg, 61%) Melting point: 97-98 ° C Cala (c = 1, CHCIs) = +33.2 IR: vmax (cm "1) : 3326, 3273 (NH), 1666, 1655, 1631 (CO), 1523 (NH). 1 H NMR (dH, 500 MHz, CDCl 3): 6.87 (1H, d, J 5.5, CHNH), 6.66-6.48 ( 1H, br m, CH2NH), 4.50 (1H, dd, J 11, 6, CHNH), 3.30-3.16 (2H, m, CH2NH), 2.18 (2H, t, J 7.5, CH2CONH), 2.04 (1H , br d, J 13.5, CH ring), 2.00-1.92 (1H, m, CH ring), 1.86-1.74 (2H, m, CH ring), 1.59 (2H, br qn J 7.0, CH2CH2CONH), 1.43 (1H, br q, J 12.5, CH ring), 1.31 (IH, brq, J 13, CH ring), 1.31-1.13 (20H, m, (CH2) 10) and 0.85 (3H, t, J 6.5, CH3). NMR with 13 C (dc, 125 MHz, CDCl 3): 175.9, 172.3 (CO), 52.0 (NHCHCO), 42.1 (NCH2), 36.6, 31.9, 31.7, 29.6 (x4), 29.4, 29.3 (x2), 29.2, 28.8 , 27.9, 25.6, 22.6 (CH2) and 14.1 (CH3). m / z (C20H38N2O2Na): 361.28270 (Calculated: 361.2831).

EXAMPLE 7: rft) -3-HEXADECANOILAMINO-CAPROLACTAMA: Hydro-pyrrolidine-5-carboxylate of (R, R) -3-amino-caprolactam (5 mmol) and Na2CO3 (15 mmol) in water (25 mL) was added to a solution of haxadecanoyl chloride (5 mmol) in dichloromethane (25 mL) at room temperature and the reaction mixture was stirred for 2 hours. The organic layer was then separated and the aqueous phase was extracted with additional dichloromethane (2 x 25 mL). The combined organic layers were dried over Na2CO3 and reduced in vacuo. The residue was purified by recrystallization from EtOAc to give the titled compound (1.23 g, 67%). Melting point: 99-100 ° C. M (c = 1, CHCI3) = -32.0.

EXAMPLE 8: fS) -3-OCTADECANOILAMINO-CAPROLACTAMA (5) -3-Amino-caprolactam hydrochloride (2 mmol) and Na2CO3 (6 mmol) in water (25 mL) were added to a solution of octadecanoyl chloride (2 mmol) in dichloromethane (25 mL) at room temperature and the reaction mixture was stirred for 2 hours. The organic layer was then separated and the aqueous phase was extracted with additional dichloromethane (2 x 25 mL). The combined organic layers were dried over Na2CO3 and reduced in vacuo. The residue was purified by recrystallization from EtOAc to give the titled compound (648 mg, 82%). Melting point: 87-88 ° C. [«]« (C = 1, CHCI3) = +31.9. IR: vmax (cm'1): 3327, 3272 (NH), 1667, 1655, 1631 (CO), 1524 (NH). 1 H NMR (dH, 500 MHz, CDCl 3): 6.88 (1H, d, J 5. 5, CHNH), 6.72-6.58 (1H, br m, CH2NH), 4.50 (1H, dd, J 11, 6, CHNH), 3. 29-3.16 (2H, m, CH2NH), 2.17 (2H, t, J 7.5, CH2CONH), 2.03 (1H, br d, J 13, CH ring), 1.99-1.90 (1H, m, CH ring), 1.86 - 1.73 (2H, m, CH ring), 1.58 (2H, br qd J 7.0, CH2CH2CONH), 1.42 (1H, br qd, J 14, 3, CH ring), 1.38-1.30 (1H, br m, CH ring ), 1.30-1.14 (28H, m, (CH2) 14) and 0.84 (3H, t, J 6.5, CH3). NMR with 13 C (dc, 125 MHz, CDCl 3): 175.9, 172.3 (CO), 52.0 (NHCHCO), 42.1 (NCH2), 36.6, 31.9, 31.7, 29.6 (x8), 29.4, 29.3 (x2), 29.2, 28.8 , 27.9, 25.6, 22.6 (CH2) and 14.1 (CH3). m / z (C24H46N2O2Na): 417.34460 (Calculated: 417.3457).

EXAMPLE 9: ÍS) - (Z) -3- (HEXADEC-9-ENOlL) AMINO- CAPROLACTAMA: Hydro-pyrrolidine-5-carboxylate of (S, S) -3-amino-caprolactam (2 mmol) and Na2CO3 (6 mmol) in water (25 mL) were added to a solution of (Z) -hexadec-9 chloride. -neoyl (2 mmol) in dichloromethane (25 mL) at room temperature, and the reaction mixture was stirred for 2 hours. The organic layer was separated and the aqueous phase was extracted with additional dichloromethane (2x 25 mL). The combined organic layers were dried over Na2CO3 and reduced in vacuo. The residue was purified by column chromatography on silica gel (eluent: EtOAc for 9: 1 EtOAc: MeOH) to give the titled compound (406 mg, 56%). Melting point: 67-68 ° C. [a3a (c = 1, CHCI3) = + 33.2. IR: vmax (cm "1): 3324, 3268 (NH), 1655, 1630 (CO), 1524 (NH). 1 H NMR (dH, 500 MHz, CDCl 3): 6.88 (1H, d, J 5.5, CHNH), 6.67 (1H, br s, CH 2 NH), 5.33-5.25 (2H, m, CH = CH), 4.50 (1H , ddd, J 11.6, 1, CHNH), 3.29-3.16 (2H, m, CH2NH), 2.17 (2H, t, J 7.5, CH2CONH), 2.03 (1H, br d, J 13, CH ring), 1.99-1.90 (5H, m, ring CH + CH2CH = CHCH2), 1.84-1.72 (2H, m, CH ring), 1.58 (2H, br qn J 7.0, CH2CH2CONH), 1.43 (1H, br qd, J 14, 3, CH ring), 1.38-1.30 (1H, br m, CH ring), 1.30-1.14 (16H, m, (CH2) 4CH2CH = CHCH2 (CH2) 4) and 0.84 (3H, t, J7, CH3). 3 C NMR (dc, 125 MHz, CDCl 3): 175.9, 172.3 (CO), 129.8 (x2) (CH = CH), 52.0 (NHCHCO), 42.0 (NCH2), 36.6, 31.7 (x2), 29.7 (x2) , 29.2 (x2), 29.1, 29.0, 28.8, 27.9, 27.2, 27.1, 25.6, 22.6 (CH2) and 14.1 (CH3). m / z (C22H40N2O2Na): 387.29700 (Calculated: 387. 2987).

EXAMPLE 10: fS) - (Z -3- (OCTADEC-9-ENOIL) AMINO- CAPROLACTAMA Hydro-pyrrolidine-5-carboxylate of (S, S) -3-amino-caprolactam (2 mmol) and Na2CO3 (6 mmol) in water (25 mL) were added to a solution of (Z) -octadec-9 chloride. -neoyl (2 mmol) in dichloromethane (25 mL) at room temperature, and the reaction mixture was stirred for 2 hours. The organic layer was separated and the aqueous phase was extracted with additional dichloromethane (2 x 25 mL). The combined organic layers were dried over Na2CO3 and reduced in vacuo. The residue was purified by column chromatography on silica gel (eluent: EtOAc for 9: 1 EtOAc: MeOH), to give the titled compound (514 mg, 66%). Melting point: 66-67 ° C. [af¿ (C = 1, CHCIs) = +30.9. IR: vmax (cm-1): 3327, 3268 (NH), 1655, 1631 (CO), 1523 (NH). NMR with 1H (dH, 500 MHz, CDCl 3): 6.88 (1H, d, J 5.5, CHNH), 6.74 (1H, br t, J5, CH2NH), 5.33-5.24 (2H, m, CH = CH), 4.49 (1H, ddd, J 11, 6, 1.5, CHNH), 3.29-3.14 (2H, m, CH2NH), 2.16 (2H, t, J 7.5, CH2CONH), 2.03 (1H, br d, J 13.5, CH ring ), 1.99-1.89 (5H, m, ring CH + CH2CH = CHCH2), 1.84-1.72 (2H, m, CH ring), 1.58 (2H, br qn J 7.0, CH2CH2CONH), 1.42 (1H, br qd, J 14, 3, CH ring), 1.38-1.30 (1H, br m, CH ring), 1.30-1.14 (20 H, m, (CH2) 6CH2CH = CHCH2 (CH2) 4) and 0.83 (3H, t, J 7 , CH3). NMR with 13 C (dC, 125 MHz, CDCl 3): 175.9, 172.3 (CO), 129. 9. 129.7 (CH = CH), 52.0 (NHCHCO), 42.0 (NCH2), 36.6, 31.8, 31.7, 29.7 (x2), 29.5, 29.3 (x3), 29.2, 29.1, 28.8, 27.9, 27.2, 27.1, 25.6 , 22.6 (CH2) and 14.1 (CH3). m / z (C24H4 N2O2Na): 415.32820 (Calculated: 415.3300).

EXAMPLE 11: rfl) - (Z) -3- (OCTADEC-9-ENOIL) AMINO- CARPROLACTAMA Hydro-pyrrolidine-5-carboxylate of (R, R) -3-amino-caprolactam (2 mmol) and Na2CO3 (6 mmol) in water (25 mL) were added to a solution of (Z) -octadec-9 chloride. -neoyl (2 mmol) in dichloromethane (25 mL) at room temperature, and the reaction mixture was stirred for 2 hours. The organic layer was separated and the aqueous phase was extracted with additional dichloromethane (2 x 25 mL). The combined organic layers were dried over Na2CO3 and reduced in vacuo. The residue was purified by column chromatography on silica gel (eluent: EtOAc to 9: 1 EtOAc: MeOH) to give the titled compound (574 mg; 73%). Melting point: 66-67 C. M5 (c = 1, CHCl3) = -31.4.

EXAMPLE 12: < rS) -3- (2'.2'-DIMETHYL-DODECANOIL) AMINO- CAPROLACTAMA: Hydro-pyrrolidine-5-carboxylate of (S, S) -3-amino-caprolactam (2 mmol) and Na2CO3 (6 mmol) in water (25 mL) were added to a solution of 2,2-dimethyI-dodecanoyl chloride (2 mmol) in dichloromethane (25 mL) at room temperature and the reaction mixture was stirred for 2 hours. The organic layer was separated and the aqueous phase was extracted with additional dichloromethane (2 x 25 mL). The combined organic layers were dried over Na2CO3 and reduced in vacuo. The residue was purified by column chromatography on silica gel (eluent: EtOAc for 9: 1 EtOAc: MeOH) to give the titled compound (543 mg, 80%). Melting point: 41-42 ° C. . { & amp; (C = 1, CHCI3) = +28.0. IR: vmax (cm "1): 3403, 3265 (NH), 1673, 1641 (CO), 1497 (NH). 1 H NMR (dH, 500 MHz, CDCl 3): 7.08 (1H, d, J 5.5, CHNH ), 6.67 (1H, br s, CH2NH), 4.44 (1H, dd, J 11, 5.5, CHNH), 3.28-3.15 (2H, m, CH2NH), 2.01 (1H, br d, J 13, CH ring) 1.98-1.89 (1H, m, CH ring), 1.84-1.72 (2H, m, CH ring), 1.47-1.30 (3H, br m, CH + CH2CMe2CONH ring), 1.27-1.15 (17H, br m, ring CH + (CH2) 8) 1.13 (3H, s, CMeMe), 1.12 (3H, s, CMeMe) and 0.82 (3H, t, J7, CH2CH3). NMR with 13C (dc, 125 MHz, CDCl 3): 177.1, 176.0 (CO), 52.0 (NHCHCO), 41.9 (CMe2), 42.1, 41.3, 31.8, 31.5, 30.1, 29.6, 29.5 (x2), 29.3, 28.9, 27.9 (CH2), 25.3, 25.2 (CH3), 24.8, 22.6 (CH2) and 14.1 (CH3) m / z (C20H38N2O2Na): 361.28350 (Calculated: 361.2831) Compound 12 was subsequently resynthesized on a larger scale, and this batch of material had the following properties: Melting point 51-52 ° C. (c = 1, CHCl3) + 28.0, M (c = 0.87, MeOH) +13.3.

EXAMPLE 13: fS) -3- (DECILOXICARBONIL) AMINO-CAPRQLACTAMA Hydro-pyrrolidine-5-carboxylate of (S, S) -3-amino-caprolactam (2 mmol) and Na2CO3 (6 mmol) in water (25 mL) was added to a solution of decyl chloroformate (2 mmol) in dichloromethane ( 25 mL) at room temperature and the reaction mixture was stirred for 2 hours. The organic layer was separated and the aqueous phase was extracted with additional dichloromethane (2 x 25 mL). The combined organic layers were dried over Na2CO3 and reduced in vacuo. The residue was purified by column chromatography on silica gel (eluent: EtOAc for 9: 1 EtOAc: MeOH) to give the titled compound (459 mg, 74%). Melting point: 40-41 ° C.

IR: vmax (cm "1): 3352,3300 (NH), 1682, 1657, 1637 (CO), 1513 (NH). NMR with 1H (dH, 500 MHz, CDCl 3): 6.86 (1H, br s, CH 2 NH), 6.72 (1H, d, J 6 CHNH), 4.49 (1H, dd, J 11, 6, CHNH), 3.99 (2H , t, J 6, OCH2), 3.26-3.14 (2H, m, CH2NH), 2.04 (1H, br d, J 13.5, CH ring), 2.00-1.91 (1H, m, CH ring), 1.82-1.68 ( 2H, m, CH ring), 1.55 (2H, br qn J 7.0, CH2CH2O), 1.48 (1H, br qd, J 14, 2.5, CH ring), 1.38-1.31 (1H, br m, CH ring), 1.29 -1.17 (14H, m, (CH2) 7) and 0.83 (3H, t, J 7, CH3). NMR with 13 C (dc, 125 MHz, CDCl 3): 175.8, 155.9 (CO), 65.0 (OCH2), 53.5 (NHCHCO), 42.0 (NCH2), 32.1, 31.8, 29.5 (x2), 29.2 (x2), 29.0, 28.8, 28.0, 25.8, 22.6 (CH2) and 14.1 (CH3). m / z (C 17 H 32 N 2 O 3 N a): 335.23190 (Calculated: 335.2311).

EXAMPLE 14: fS) - < ?) - 3- (DODEC-2-ENOIL) AMINO-CAPROLACTMA Hydro-pyrrolidine-5-carboxylate of (S, S) -3-amino-caprolactam (2 mmol) and Na2CO3 (6 mmol) in water (25 mmol) were added. mL) was added to a solution of dodec-2-enoyl chloride (2 mmol) in dichloromethane (25 mL) at room temperature, and the reaction mixture was stirred for 2 hours. The organic layer was separated and the aqueous phase was extracted with additional dichloromethane (2x 25 mL). The combined organic layers were dried over Na2CO3 and reduced in vacuo. The residue was purified by column chromatography on silica gel (eluent: EtOAc for 9: 1 EtOAc: MeOH) to give the titled compound (472 mg, 77%). Melting point: 87-88 ° C. [f¿ (c = 1, CHCI3) = +44.7. IR: vmax (crn "1): 3382, 3331 (NH), 1660, 1616 (CO), 1520 (NH). 1 H NMR (dH, 500 MHz, CDCl 3): 6.94 (1H, d, J 5.5, CHNH), 6.84 (1H, br s, CH 2 NH), 6.78 (1H, dt, J 15.5, 7, CH 2 CH = CH), 5.80 (1H, d, J 15.5, CH2CH = CH), 4.56 (1H, ddd, J 11, 6, 1.5, CHNH), 3.29-3.15 (2H, m, CH2NH), 2.11 (2H, q, J 7, CH2CH = CH), 2.07 (1H, br d, J 13.5, CH ring ), 1.98-1.90 (1H, m, CH ring), 1.86-1.73 (2H, m, CH ring), 1.44 (1H, br qd, J 14, 2.5, CH ring), 1.41-1.29 (3H, br m , ring CH + CH2CH2CH = CH), 1.29-1.14 (12H, m, (CH2) 6) and 0.82 (3H, t, J 6.5, CH3). NMR with 13 C (dc, 125 MHz, CDCl 3): 175.9, 165.0 (CO), 144.8, 123.5 (CH = CH), 52.0 (NHCHCO), 42.0 (NCH2), 32.0, 31.8, 31.6, 29.4 (x2), 29.2 , 29.1, 28.8, 28.2, 27.9, 22.6 (CH2) and 14.1 (CH3). m / z (C 18 H 32 N 2 O 2 Na): 331.23570 (Calculated: 331.2361).

EXAMPLE 15: ÍS) -3- (DEC-9-ENILAMINOCARBONIL) AMlNO- CAPROLACTAMA Hydro-pyrrolidine-5-carboxylate of (S, S) -3-amino-caprolactam (2 mmol) and Na2CO3 (6 mmol) in water (25 mL) were added to an isocyanate solution of dec-9-enylo mmol) in dichloromethane (25 mL) at room temperature and the reaction mixture was stirred for 2 hours. The organic layer was separated and the aqueous phase was extracted with additional dichloromethane (2x 25 mL). The combined organic layers were dried over Na2CO3 and reduced in vacuo. The residue was purified by column chromatography on silica gel (eluent: EtOAc for 9: 1 EtOAc: MeOH) to give the titled compound (347 mg, 56%). Melting point: 98-99 ° C. Falls off? (c = 1, CHCI3) = +27.3. IR: vmax (cm'1): 3365, 3327, 3276 (NH), 1619, (CO), 1551 (NH). 1 H NMR (dH, 500 MHz, CDCl 3): 6.64 (1H, br s, ring CH2NH), 6.12 (1H, d, J6 CHNH), 5.75 (1H, ddtd, J17, 10, 6.5, 1.5, CH2 = CH), 5.21-5.12 (1H, br m, urea CH2NH), 4.93 (1H, dq, J 17, 1.5, CHH = CH), 4.87 (1H, br d, J 10, CHH = CH), 4.49 (1H, dd, J 11, 6, NHCHCO), 3.25 (1H, ddd, J 15.5, 12, 4, ring CH2N) , 3.17 (1H, dt, J 14, 6, CH2N ring), 3.11-3.02 (2H, m, urea NHCH2), 2.05-1.87 (4H, brm, CH ring x2 + CH2CH = CH), 1.82-1.70 ( 2H, m, CH ring), 1.48- 1.36 (3H, br m, CH2CH2NH chain, + CH ring), 1.36-1.27 (3H, m, CH + CH2 chain ring) and 1.27-1.17 (8H, m, chain ( CH2) 4). NMR with 13 C (dc, 125 MHz, CDCl 3): 177.2, 157.6 (CO), 139. 1, 114.1 (CH = CH), 52.7 (NHCHCO), 42.1, 40.3 (NCH2), 33.7, 32.9, 30.3, 29.4, 29.3, 29.0, 28.8 (x2), 27.9 and 26.9 (CH2). m / z (C? 7H3? N3O2Na): 332.23150 (Calculated: 332.2314).

EXAMPLE 16: fS) -3- (DECILAMINOCARBONIL) AMINO- CAPROLACTMA Hydro-pyrrolidine-5-carboxylate of (S, S) -3-amino-caprolactam (2 mmol) and Na2CO3 (6 mmol) in water (25 mL) were added to a solution of decyl isocyanate (2 mmol) in dichloromethane (25 mL) at room temperature and the reaction mixture was stirred for 2 hours. The organic layer was separated and the aqueous phase was extracted with additional dichloromethane (2x 25 mL). The combined organic layers were dried over Na2CO3 and reduced in vacuo. The residue was purified by column chromatography on silica gel (eluent: EtOAc to 9: 1 EtOAc: MeOH) to give the titled compound (401 mg, 64%). Melting point: 97-98 ° C. L? Fp (c = 1, CHCI3) = +27.7. IR: vmax (cm "1): 3359, 3316 (NH), 1621, (CO), 1558 (NH). 1 H NMR (dH, 500 MHz, CDCl 3): 6.62 (1 H, br s, CH 2 NH ring), 6.09 (1 H, d, J 6 CHNH), 5.16 (1 H, br t, J 5, urea CH 2 NH), 4.48 ( 1H, ddd, J 11, 6, 1, NHCHCO), 3.26 (1H, ddd, J 16, 11, 5, ring CH2N), 3.17 (1H, dt, J 15, 7, ring CH2N), 3.11-3.02 ( 2H, m, urea NHCH2), 2.02 (1H, brd J14, CH ring), 1.96-1.87 (1H, m, CH ring), 1.83-1.70 (2H, m, CH ring), 1.48-1.27 (4H, br m, CH x2 ring + CH2 chain), 1.27-1.14 (14H, m, (CH2) 7) and 0.82 (3H, t, J7, CH3). NMR with 13 C (dC, 125 MHz, CDCl 3): 177.2, 157.6 (CO), 52.7 (NHCHCO), 42.1, 40.4 (NCH2), 32.9, 31.8, 30.2, 29.6, 29.5,. 29.4, 29.3, 28.8, 27.9, 26.9, 22.6 (CH2) and 14.1. m / z (C17H33N3O2Na): 334.24880 (Calculated: 334.2470).

EXAMPLE 17: rR) -3- (2'.2'-DlMETIL-DODECANOIL) AMINO- CAPROLACTMA Hydro-pyrrolidine-5-carboxylate of (R, R) -3-amino-caprolactam (2 mmol) and Na2CO3 (6 mmol) in water (25 mL) were added to a solution of 2,2-dimethyl-dodecanoyl chloride (2 mmol) in dichloromethane (25 mL) at room temperature, and the reaction was stirred for 2 hours. The organic layer was separated and the aqueous phase was extracted with additional dichloromethane (2x 25 mL). The combined organic layers were dried over Na2CO3 and reduced in vacuo. The residue was purified by column chromatography on silica gel (EtOAc: hexanes 1: 3 to EtOAc), to give (Rj-3- (2 ', 2'-d, methyl-dodecanoyl) amino-caprolactam (515 mg, 76%); Melting point: 48-49 ° C; [«£? (0 = 1, CHCl3) -25.7; & (c = 0.5, MeOH) -12.2. Subsequently, compound 17 was resynthesized on a larger scale, and this batch of material had the following properties: Melting point 50-51 ° C.

EXAMPLE 18: fS) -3- (2'.2'-DIMETHYL PENTANOIL) AMINO- CAPROLACTMA Hydro-pyrrolidine-5-carboxylate of (S, S) -3-amino-caprolactam (20 mmol) and Na2CO3 (60 mmol) in water (50 mL) were added to a solution of 2,2-dimethyl-pentanoyl chloride (20 mmol) in dichloromethane (50 mL) at room temperature, and the reaction was stirred for 12 hours. The organic layer was separated and the aqueous phase was extracted with additional dichloromethane (2 x 25 mL). The combined organic layers were dried over Na2CO3 and reduced in vacuo. The residue was recrystallized from EtOAc / hexane to give (S) -3- (2 ', 2'-dimethyl-pentanoyl) amino-caprolactam (3.50 g, 77%); Melting point: 84-85 ° C; vma? / cm-1 3387, 3239 (NH), 1655, 1634 (CO), 1507 (NH); dH (500 MHz, CDCIs) 7.08 (1H, d, J 5, CHNH), 6.53 (1H, br s, CH2NH), 4.45 (1H, ddd, J 11, 5.5, 1.5, CHNH), 3.29-3.16 (2H , m, CH2NH), 2.00 (1H, br d, J 13, CH ring), 1.98-1.92 (1H, m, CH ring), 1.84-1.73 (2H, m, CH ring), 1.47-1.30 (4H, br m, ring CH x2 + CH2CMe2CONH), 1.23-1.15 (2H, m, CH2CH3) 1.14 (3H, s, CMeMe), 1.13 (3H, s, CMeMe) and 0.84 (3H, t, J7, CH2CH3); dc (125 MHz, CDCI3) 177.0, 176.1 (CO), 52.1 (NHCHCO), 43.6, 42.0 (x2, one of which is CMe2), 31.5, 28.9, 27.9 (CH2), 25.3, 25.2 (CH3), 18.0 (CH2) and 14.5 (CH3); m / z (M + C13H24N2O2 requires 240.18378) 240.18437.

EXAMPLE 19: rS) -3- (2'.2'-DIMETHYL-PENT-4-ENOIL) AMINO- CAPROLACTMA Hydro-pyrrolidine-5-carboxylate of (S, S) -3-amino-caprolactam (20 mmol) and Na2CO3 (60 mmol) in water (50 mL) were added to a solution of 2,2-dimethyl-pent-chloride. 4-enoyl (20 mmol) in dichloromethane (50 mL) at room temperature and the reaction was stirred for 2 hours. The organic layer was separated and the aqueous phase was extracted with additional dichloromethane (2x 25 mL). The combined organic layers were dried over Na2CO3 and reduced in vacuo. The residue was purified by column chromatography on silica gel (1: 1 EtOAc: hexane for EtOAc) to give fSj-3- (2 ', 2, -dimethyl-pent-4-eneyl) amino-caprolactam (1.43 g, 32%); Melting point: 71-72 ° C; M5 (c = 1, CHCl3) +27.7; Vmax / cm "1 3395, 3304 (NH), 1675, 1633 (CO), 1534 (NH), dH (500 MHz, CDCl 3) 7.10 (1H, d, J 4.5, CHNH), 6.48 (1H, br s, CH2NH), 5.68 (1H, ddt, J 17, 10, 7.5, CH = CH2), 5.02 (1H, br d, J 17 CH = CHH), 5.00 (1H, br d, J 10, CH = CHH), 4.45 (1H, dd, J 11, 5.5, CHNH), 3.30-3.17 (2H, m, CH2NH) 2.27 (1H, J 14, 7.5, CHHCH = CH2), 2.22 (1H, dd, J 14, 7.5, CHHCH = CH2), 2.01 (1H, br d, J 13, CH ring), 1.98-1.92 (1H, m, CH ring), 1.85-1.73 (2H, m, CH ring), 1.47-1.30 (2H, br m , ring CH x2), 1.16 (3H, s, CMeMe) and 1.15 (3H, s, CMe e); dc (125 MHz, CDCI3) 176.4, 175.9 (CO), 134.2 (CH = CH2), 117.8 (CH = CH2), 52.1 (NHCHCO), 45.2, 42.1 (CH2), 41.9 (CMe2), 31.5, 28.9, 27.9 (CH2), 25.0 and 24.9 (CH3); m / z (M + C13H22N2O2 requires 238.16813) 238.16834.

EXAMPLE 20: rS) -3- (2 ', 2'-DIMETHYL-PROPIONlL) AMINO- CAPROLACTMA Phosphoryl-pyrrolidine-5-carboxylate of (S, S) -3-amino-caprolactam (5 mmol) and Na2CO3 (15 mmol) in water (15 mL) were added to a solution of 2,2-dimethyl chloride. -propionyl (5 mmol) in dichloromethane (15 mL) at room temperature, and the reaction was stirred for 12 hours. The organic layer was separated and the aqueous phase was extracted with additional dichloromethane (2x 25 mL). The combined organic layers were dried over Na2SO4 and reduced in vacuo. The residue was recrystallized from EtOAc / hexane to give (S) -3- (2 ', 2'-dimethyl-propionyl) amino-caprolactam (645 mg, 61%); Melting point: 126-127 ° C; C «3fl (C = 1, CHCl3) +39.5; Vmax / cm "1 3381, 3255 (NH), 1680, 1632 (CO), 1506 (NH); 8H (500 MHz, CDCl 3) 7.10 (1H, d, J 5.0, CHNH), 6.75 (1H, br s, CH2NH), 4.42 (1H, ddd, J 11, 5.5, 1.5, CHNH), 3.27-3.16 (2H, m, CH2NH), 2.03-1.89 (2H, m, 2x CH ring), 1.83-1.71 (2H, m , 2x CH ring), 1.45-1.28 (2H, m, 2x CH ring) and 1.15 (9H, s, 3x CH3), dc (125 MHz, CDCI3) 177.7, 176.1 (CO), 52.1 (NHCHCO), 42.0 ( CH2N), 40.5 (CCO), 31.5, 28.9, 27.9 (CH2 lactam), 27.4 (3x CH3) .m / z (MNa + C11H20N2O2Na requires 235.141699) 235. 142237; (MH + C.MH21N2O2 requires 213.1597543) 213.160246 EXAMPLE 21: rS) -3- (2'.2'-DIMETHYL-BUTIRIL) AMINQ- CAPROLACTMA Hydro-pyrrolidine-5-carboxylate of (S, S) -3-amino-caprolactam (5 mmol) and Na2CO3 (15 mmol) in water (15 mL) were added to a solution of 2,2-dimethyl-butyryl chloride. (5 mmol) in dichloromethane (15 mL) at room temperature, and the reaction was stirred for 12 hours. The organic layer was then separated and the aqueous phase was extracted with additional dichloromethane (2 x 25 mL). The combined organic layers were dried over Na2SO and reduced in vacuo. The residue was recrystallized from EtOAc / hexane to give (S) -3- (2 ', 2'-dimethylpropionyl) amino-caprolactam (562 mg, 50%); Melting point: 106-107 ° C; 0 * 3 * (c = 1, CHCI3) +33.6; vmax / cm-1 3400, 3278 (NH), 1677.1630 (CO), 1500 (NH); dH (500 MHz, CDCl 3) 7.08 (1H, d, J 5.0, CHNH), 6.72 (1H, br s, CH 2 NH), 4.44 (1H, ddd, J 11, 5.5, 1.5, CHNH), 3.28-3.16 (2H , m, CH2NH), 2.04-1.90 (2H, m, 2x CH ring), 1.83-1.72 (2H, m, 2x CH ring), 1.57-1.44 (2H, m, CH2CH3), 1.44-1.30 (2H, m , 2x CH ring) 1.12 (3H, s, CH3) 1.11 (3H, s, CH3) and 0.78 (3H, t, J 7.5, CH2CH3); dc (125 MHz, CDCl 3) 177.0, 176.0 (CO), 52.1 (NHCHCO), 42.2 (CCO), 42.0 (CH2N), 33.7 (CH2CH3), 31.6, 28.9, 27.9 (CH2 lactam), 24.8, 24.7 (CCH3) and 9.1 (CH2CH3); m / z (MH + C12H23N2O2 requires 227.1760) 227.1767.

EXAMPLE 22: fS, Ej-3-f2'.2'-DIMETHYL-DODEC-4'-ENOIL) AMINO-CAPROLACTMA: Hydro-pyrrolidine-5-carboxylate of (S, S) -3-amino-caprolactam (10 mmol) and Na2CO3 (30 mmol) in water (30 mL) were added to a solution of 2,2-dimethyl-dodec chloride. -2-enoyl (crude, from the previous reaction) (10 mmol) in dichloromethane (30 mL) at room temperature, and the reaction was stirred for 12 hours. The organic layer was then separated and the aqueous phase was extracted with additional dichloromethane (2x 25 mL). The combined organic layers were dried over Na2CO3 and reduced in vacuo. The residue was purified by column chromatography on silica gel (1: 1 EtOAc: hexanes for EtOAc) to give (SE) -3- (2 ', 2'-dimethyl-dodec-4, -enoyl) aminocaprolactam as an oil colorless (2.12 g, 63%); M * (c = 1, CHCl3) +21.6; vmax / cm-1 3264 (NH), 1639 (CO), 1497 (NH); dH (500 MHz, CDCl 3) 7.09 (1H, d, J 5.5, CHNH), 6.67-6.32 (1H, br m, CH 2 NH) 5.42 (1H, dt, J 15, 6.5, CH = CH), 5.28 (1H, dt, J 15, 7, CH = CH), 4.44 (1H, dd, J 11, 5.5, CHNH), 3.30-3.17 (2H, m, CH2NH), 2.20 (1H, dd, 13.5, 7, CH = CHCH2 ), 2.14 (1H, dd, 13.5, 7, CH = CHCH2), 2.01-1.87 (4H, brm, ring CH x2, + CH2CH = CH), 1.87-1.74 (2H, m, CH ring), 1.47- 1.32 (2H, m, CH ring), 1.27-1.15 (10H, br m, (CH2) 5) 1.13 (3H, s, CMeMe), 1.12 (3H, s, CMe e) and 0.83 (3H, t, J7 , CH2CH3); dc (125 MHz, CDCI3) 176.8, 176.0 (CO), 134.2, 125.2 (CH = CH), 52.1 (NHCHCO), 43.9 (CH2), 42.1 (x2) (CH2 + CMe2), 32.6, 31.8, 31.5, 30.1 , 29.4, 29.1 (x2), 28.9, 27.9 (CH2), 25.0, 24.8 (CH3) and 22.6 (CH3); m / z (MH + C2oH37N2O2 requires 337.2855) 337.2858.

EXAMPLE 23: rS) -3- (2'.2'.5'-TRIMETHYL-HEX-4'-ENOIL) AMINO- CAPROLACTMA Hydro-pyrrolidin-5-carboxylate of (S, S) -3-amino-caprolactam (4.11 g, 16 mmol) and Na2CO3 (5.09 g, 48 mmol) in water (50 mL) were added to a 2-chloro-2-caprolactam solution. , 2,5-trimethyl-hex-4-enoyl (16 mmol) in dichloromethane (50 mL) at room temperature, and the reaction was stirred for 12 hours. Then the organic layer was separated and the aqueous phase was extracted with additional dichloromethane (2 x 50 mL). The combined organic layers were dried over Na2CO3 and reduced in vacuo. The residue was purified by column chromatography on silica gel (1: 5 EtOAc: hexanes for EtOAc) to give (SJ-3- (2 ', 2', 5 '~ trimethyl-hex-4'-enoyl) amino- caprolactam as a waxy solid (3.58 g, 84%); Melting point: 43-44 ° C; M "(c = 1, CHCl3) +23.2; vmax / cm-1: 3394, 3251 (NH), 1674, 1633 (CO), 1503 (NH), dH (500 MHz, CDCI3) 7.11 (1H, d, J 5.0, CHNH), 6.65-6.45 (1H, br m, CH2NH), 5.04 (1H, t, J 7.5, CH = C), 4.44 (1H, ddd, J 11, 5.5, 1.5, CHNH), 3.24- 3.16 (2H, m, CH2NH), 2.20 (1H, dd, J 14.5, 7.5, C = CHCH2), 2.15 (1H, dd, J, 14.5, 7.5, C = CHCH2), 2.03-1.90 (2H, m, 2x CH ring), 1.84-1.72 (2H, m, 2x CH ring), 1.65 (3H, s, CH3), 1.56 (3H, s, CH3), 1.45-1.28 (2H, m, 2x CH ring), 1.13 (3H, s, CH3) and 1.12 (3H, s, CH3); dc (125 MHz, CDCI3) 176.9, 176.0 (CO), 134.1, 119.9 (CH = CH), 52.1 (NHCHCO), 42.5 (CH2CMe2), 42.1 (CH2N), 39.0, 31.5, 28.9, 28.0 (CH2 lactam), 26.0, 25.0, 24.9, 17.9 (CH3); m / z (MH + C? 5H27N2O2 requires 267.2073) 267.2063.

EXAMPLE 24: IS) -3- (2 ', 2', 5'-TRIMETHYL-HEXANOIL) AMINO- CAPROLACTMA S,) - 3- (2,, 2,, 5'-trimethyl-hex-4, -enoyl) amino-caprolactam (400 mg) was dissolved in EtOAc (25 mL), palladium hydroxide on charcoal ( 20%, ca 100 mg) and the mixture was stirred at room temperature under a hydrogen atmosphere for 14 hours. The reaction was then filtered through a pad of Celite® and the solvent removed in vacuo to give (S) -3- (2 2 ', 5'-trimethyl-hexanoyl) amino-caprolactam as a waxy solid (400 mg , 98%); Melting point: 73-74 ° C; M5 (C = 1, CHCl3) +27.8; vmax / cm "1 3249 (NH), 1654, 1638 (CO), 1502 (NH); dH (500 MHz, CDCl 3) 7.08 (1H, d, 'J 5.0, CHNH), 6.75-6.55 (1H, brm, CH2NH), 4.44 (1H, ddd, J 11, 5.5, 1.5, CHNH), 3.29-3.16 ( 2H, m, CH2NH), 2.03-1.91 (2H, m, 2x CH ring), 1.84-1.73 (2H, m, 2x ring CH), 1.47-1.28 (5H, m, 2x ring CH + CH2 + CH (CH3) 2), 1.13 (3H, s, CH3), 1.12 (3H, s, CH3), 1.08-1.02 (2H, m, CH2), 0.82 (3H, s, CH3), 0. 80 (3H, s, CH 3); dc (125 MHz, CDCl 3) 177.1, 176.1 (CO), 52.1 (NHCHCO), 42.1 (CH2N), 41.9 (CH2CMe2), 39.0, 33.7, 31.5, 28.9 (CH2), 28.4 (Me2CH), 27.9 (CH2), 25.3, 25.2, 22.6, 22.5 (CH3); m / z (MH + C15H29N2O2 requires 269.2229) 269.2219.

EXAMPLE 25: ÍSJ-3- (11 '-BROMO-UNDECANOIL) AMINO- CAPROLACTAMA (S) -3-amino-caprolactam hydrochloride (5 mmol) and Na2CO3 (15 mmol) in water (25 mL) were added to a solution of 11-bromo-undecanoal chloride (5 mmol) in dichloromethane (25 mL). at room temperature, and the reaction was stirred for 4 hours. The organic layer was then separated and the aqueous phase was extracted with additional dichloromethane (2 x 25 mL). The combined organic layers were dried over Na2CO3 and reduced in vacuo. The residue was purified by recrystallization from EtOAc to give (S) -3- (11'-bromo-undecanoyl) amino-caprolactam (1.49 g, 79%); Melting point: (EtOAc) 73-74 ° C; K * (C = 1, CHCl3) +31.8; vma? / cnr1 3342, 3287 (NH), 1668, 1634 (CO), 1515 (NH); dH (500 MHz, d6-DMSO) 7.76 (1H, t, J 6.5, CH2NH), 7.67 (1H, d, J7, CHNH), 4.38 (1H, dd, J 11, 7, CHNH), 3.51 (2H , t, J 6.5, CH2Br), 3.15 (1H, ddd, J 15.5, 10.5, 5, CHHNH), 3.05 (1H, dt, J 14, 7, CHHNH), 2.17-2.06 (2H, m, CH2CONH), 1.85 (1H, dt, J14.3, C-5H), 1.82-1.68 (4H, m, C-4 H, C-6 H and CH2CH2Br), 1.62 (1H, qt, J 12, 3.5, C -5 H), 1.46 (2H, br qn J 6.5, CH2CH2CONH), 1.41-1.31 (3H, m, C-4 H and CH2 chain) and 1.31-1.13 (11H, m, (CH2) 5 + C-6 H); dc (125 MHz, d6-DMSO) 174.4 (CO-ring), 171.3 (CO-chain), 51.3 (NHCHCO), 40.7 (NCH2), 35.3, 35.2, 32.4, 31.3, 29.0, 28.9 (x3), 28.7, 28.2, 27.8, 27.6 and 25.4 (CH2); m / z (MH + BrC17H32N2O2 requires 375.1647) 375.1655.

EXAMPLE 26: fS) -3- (11'-AZIPO-UNDECANOIDAMINO- CAPROLACTAMA Sodium azide (650 mg, 10 mmol) was added to (S) -3- (11-bromo-undecanoyl) amine-caprolactam (375 mg, 1 mmol) in DMF (2 mL) and the mixture was heated to 0.degree. 60 ° C for 14 hours. The solvent was then removed in vacuo and the residue was partitioned between water (20 mL) and EtOAc (3 x 20 mL). The combined organic layers were washed with 1M HClq (2 x 20 mL) and then dried over Na2CO3 and reduced in vacuo. The residue was purified by recrystallization from EtOAc to give S -3- (11'-azido-undecanoyl) amino-caprolactam (221 mg, 66%); Melting point: (EtOAc) 71-72 ° C; ["£ (c = 1, CHCl3) +34.7; vmax / cm-1 3344, 3289 (NH), 2101 (N3) 1668, 1631 (CO), 1516 (NH); dH (500 MHz, d6-DMSO) 7.77 (1H, t, J 6, CH2NH), 7.67 (1H, d, J 7, CHNH), 4.38 (1H, dd, J 11.7, CHNH), 3.30 (2H, t, J 7, CH2N3), 3.15 (1H, ddd, J 15.5, 10.5, 5, CHHNH), 3.05 (1H, dt, J 14, . 5, CHHNH), 2.17-2.07 (2H, m, CH2CONH), 1.85 (1H, dt, J 14, 3.5, C-5 H), 1.82-1.68 (2H, m, C-4 H, C-6 H ), 1.62 (1H, qt, J 13, 3.5, C-5) H), 1.51 (4H, m, CH2CH2CONH and CH2CH2N3), 1.36 (1H, qd, J 13, 3, C-4 H), and 1.33-1.13 (13H, m, (CH2) 6 + C-6 H); dc (125 MHz, d6-DMSO) 174.4 (CO-ring), 171.3 (CO-chain), 51.3 (NHCHCO), 50.7 (CH2N3), 40.7 (NCH2), 35.3, 31.3, 29.0 (x2), 28.9, 28.7, 28.6, 28.3, 27.8, 26.2 and 25.4 (CH2); m / z (MNa + C17H31N5O2Na requires 360.2375) 360.2360.

EXAMPLE 27: 11'-SULPHONATE TETRAHYDRATE (S) 3- (UNDECANOIDAMINE-SODIUM CAPROLACTAMA) Sodium sulfite (630 mg, 5 mmol) in water (3 mL) was added to (S) -3- (11-bromo-undecanoyl) amino-caprolactam (375 mg, 1 mmol) in ethanol (2 mL) and The mixture was heated under reflux for 14 hours. Then, the cooled reaction mixture was added to ethanol (25 mL) and the reaction was filtered. The solvent was then removed in vacuo to give sodium (S) 3- (undecanoyl) amino-caprolactam 11'-sulfonate tetrahydrate (456 mg, 97%); Melting point: (EtOAc) 208-210 ° C; [«£? (c = 1, H2O) -15.5; vmax / cm "1 3430, 3344, 3289 (NH + H2O), 1667, 1643 (CO), 1530 (NH) 1195, 1183 (SO3, asym.), 1064 (SO3, sim.); dH (500 MHz, d6-DMSO) 7.76 (1H, t, J6, CH2NH), 7.70 (1H, d, J7, CHNH), 4.35. (1H, dd, J 10, 7.5, CHNH), 3.42 (8H, s, 4 x H2O) 3.17-3.00 (2H, m, CH2NH), 2.47-2.38 (2H, m, CH2SO3), 2.17-2.05 (2H, m, CH2CONH), 1.82 (1H, br s, J 13.5, C-5 H), 1.75-1.66 (2H, m, C -4 H, C-6 H), 1.65-1.50 (3H, m, C-5 H + CH2 chain), 1.47-1. 40 (2H, m, CH2 chain) 1. 35 (1H, qd, J 13, 3, C-4 H), and 1.30-1.11 (13H, m, (CH2) 6 + C-6 H); dc (125 MHz, d6-DMSO) 174.5 (CO-ring), 171.5 (CO-chain), 51.6 (CH2SO3), 51.4 (NHCHCO), 40.8 (NCH2), 35.3, 31.3, 29.1 (x3), 29.0 (x2), 28.8, 28.6, 27.8, 25.5 and 25.1 (CH2); m / z (MNa + C17H3? N2O5SNa2 requires 421.1749) 421.1748.

EXAMPLE 28: fS) -3- (DECANOSULFONLL) AMINO-CAPROLACTAMA FS,) - 3-amino-caprolactam hydrochloride (3 mmol) and Na2CO3 (9 mmol) in water (20 mL) were added to a solution of decanesulfonyl chloride (3 mmol) in dichloromethane (20 mL) at room temperature, and the reaction was stirred for 10 hours. The organic layer was then separated and the aqueous phase was extracted with additional dichloromethane (2x 25 mL). The combined organic layers were dried over Na2CO3 and reduced in vacuo. The residue was purified by recrystallization from EtOAc / hexanes to give (S) -3- (decanesulfonyl) amino-caprolactam (481 mg, 48%); Melting point: 98-99 ° C; M5 (c = 1, MeOH) +22.7; vmax / cm'1 3365, 3248 (NH), 1657 (CO), 1324, 1142 (SO2N); dH (500 MHz, CDCl 3) 6.35-6.18 (1 H, m, CH 2 NH), 5.71 (1 H, d, J 6, CHNH), 4.11 (1 H, ddd, J 11.5, 6, 2, CHNH), 3.31-3.18 (2H, m, CH2NH), 2.98-2.92 (2H, m, CH2SO2), 2.09 (1H, br d, J14, CH ring), 2.06-1.97 (1H, m, CH ring), 1.88-1.59 (5H , m, CH2CH2SO2 + 3 CH ring), 1.43-1.33 (3H, m, CH2 chain + CH ring), 1.32-1.18 (12H, m, CH3 (CH2) 6) and 0.86 (3H, m, CH3); dc (125 MHz, CDCl 3) 174.8 (CO) 55.5 (NHCHCO), 53.5 (CH2SO2), 40.7 (NCH2), 33.9, 31.8, 29.4, 29.3, 29.2, 29.1, 28.6, 28.3, 27.9, 23.5, 22.6 (CH2) , and 14.1 (CH3); m / z (MNa + C16H32N2O3SNa requires 355.2031) 355.2054; anal. (C 16 H 32 N 2 O 3 S requires C, 57.8, H, 9.7, N, 8.4) C, 57.8, H, 9.7, N, 8.3.

EXAMPLE 29: fS) -3- (DODECANOSULFONIL) AMINO- CAPROLACTAMA (6) -3-Amino-caproactam hydrochloride (2 mmol) and Na2CO3 (6 mmol) in water (20 mL) were added to a solution of dodecanesulfonyl chloride (2 mmol) in dichloromethane (20 mL) at room temperature, and the reaction was stirred for 10 hours.

The organic layer was then separated and the aqueous phase was extracted with additional dichloromethane (2 x 25 mL). The combined organic layers were dried over Na2CO3 and reduced in vacuo. The residue was purified by column chromatography on silica gel (3: 1 hexanes: EtOAc for 100% EtOAc) and then by recrystallization from heptane to give (SJ-S-iodocanesulfonyl) amino-caprolactam (302 mg, 42%). %); Melting point: 100-101 ° C; vmax / cm-1 3366, 3247 (NH), 1657 (CO), 1324, 1143 (SO2N); dH (500 MHz, CDCl 3) 6.66 (1H, t, J 6, CH 2 NH, 5.78 (1H, d, J 6, CHNH), 4.10 (1H, ddd, J 11, 6, 2, CHNH), 3.29-3.17 ( 2H, m, CH2NH), 2.97-2.90 (2H, m, CH2SO2), 2.12-2.03 (1H, m, CH ring), 2.03-1.96 (1H, m, CH ring), 1.88-1.59 (5H, m, CH2CH2SO2 + 3 CH ring), 1.43-1.32 (3H, m, CH + ring CH2 chain), 1.32-1.18 (16H, m) and 0.85 (3H, m, CH3); dc (125 MHz, CDCI3) 175.0 (CO ) 55.5 (NHCHCO), 53.5 (CH2SO2), 42.1 (NCH2), 33.8, 31.8, 29.6 (x2), 29.5, 29.3 (x2), 29.1, 28.6, 28.3, 27.9, 23.5, 22.6 (CH2), and 14.1 ( CH3); m / z (MNa + C18H36N2O3SNa requires 383.2339) 383.2351; anal. (C18H36N2O3S requires C, 60.0, H, 10.1, N, 7.8) C, 59.9, H, 10.2, N, 7.7.

EXAMPLE 30: ÍS) -3- (TETRADECANOSULFONIL) AMINO- CAPROLACTAMA SJ-3-amino-caprolactam hydrochloride (2 mmol) and Na2CO3 (6 mmol) in water (20 mL) were added to a solution of tetradecanesulfonyl chloride (2). mmol) in dichloromethane (20 mL) at room temperature, and the reaction was stirred for 10 hours. The organic layer was then separated and the aqueous phase was extracted with additional dichloromethane (2 x 25 mL). The combined organic layers were dried over Na2CO3 and reduced in vacuo. The residue was purified by column chromatography on silica gel (hexanes: EtOAc 3: 1 with respect to 100% EtOAc) then by recrystallization from heptane to give fSJ-3- (tetradecanesulfonyl) amino-caprolactam (373 mg, 48%); Melting point: 100-101 ° C; Vmax / cm "1 3361, 3250 (NH), 1658 (CO), 1324, 1140 (SO2N); dH (500 MHz, CDCI3) 6.64 (1H, t, J6, CH2NH), 5.74 (1H, d, J6, CHNH), 4.11 (1H, ddd, J 11.5, 6, 2, CHNH), 3.30-3.17 (2H, m, CH2NH), 2.97-2.92 (2H, m, CH2SO2), 2.12-2.05 (1H, m, ring CH), 2.05-1.96 (1H, m, CH ring), 1.87-1.59 (5H, m, CH2CH2SO2 + 3 CH ring), 1.42-1.32 (3H, m, CH + CH2 chain), 1.32-1.18 (20H , m, CH2 chain) and 0.86 (3H, m, CH3); dc (125 MHz, CDCI3) 174.9 (CO) 55.5 (NHCHCO), 53.4 (CH2SO2), 42.2 (NCH2), 33.8, 31.9, 29.6 (x4) , 29.5, 29.3 (x2), 29.1, 28.6, 28.3, 27.9, 23.5, 22.7 (CH2), and 14.1 (CH3); m / z (MNa + C20H4oN2O3SNa requires 411.2652) 411.2655; anal (C20H40N2O3S requires C, 61.8, H , 10.4, N, 7.2) C, 61.9, H, 10.5, N, 7.2.

EXAMPLE 31: fS) -3- (HEXADECANOSULFQNIL) AMlNQ- CAPRQLACTAMA: Hydrochloride of (SJ-3-amino-caprolactam (2 mmol) and Na2CO3 (6 mmol) in water (20 mL) was added to a solution of hexadecanesulfonyl chloride (2 mmol) in dichloromethane (20 mL) at room temperature, and The reaction was stirred for 10 hours, then the organic layer was separated and the aqueous phase was extracted with additional dichloromethane (2x 25 mL) The combined organic layers were dried over Na2CO3 and reduced in vacuo. The residue was purified by column on silica gel (hexanes: EtOAc 3: 1 for 100% EtOAc) and then by recrystallization from heptane to give fS,) - 3- (hexadecanesulfonyl) amine-caprolactam (553 mg, 66% ); Melting point: 100-101 ° C; vmax / cm-1 3356, 3249 (NH), 1659 (CO), 1323, 1140 (SO2N); dH (500 MHz, CDCl 3) 6.55 (1H, t, J 6, CH 2 NH), 5.76 (1H, d, J 6, CHNH), 4.11 (1H, ddd, J 11.5, 6.2, CHNH), 3.30-3.17 (2H, m, CH2NH), 2.94 (2H, t, J 8, CH2SO2), 2.12-2.04 (1H, m, CH ring), 2.04-1.97 (1H, m, CH ring), 1.87-1.58 (5H, m, CH2CH2SO2 + 3 CH ring), 1.42-1.32 (3H, m, CH + ring CH2 chain), 1.32-1.18 (24H, m, CH2 chain) and 0.86 (3H, m, CH3); dc (125 MHz, CDCl 3) 174.9 (CO) 55.5 (NHCHCO), 53.5 (CH2SO2), 42.1 (NCH2), 33.8, 31.9, 29.7 (x2), 29. 6 (x4), 29.5, 29.3 (x2), 29.1, 28.6, 28.3, 27.9, 23.5, 22.7 (CH2), and 14.1 (CH3); m / z (MNa + C20H40N2O3SNa requires 439.2965) 439.2980; anal. (C22H44N2O3S requires C, 63.4, H, 10.6, N, 6.7) C, 63.1, H, 10.6, N, 6.6.

EXAMPLE 32: (rS) -3- (OCTADECANOSULFONIL) AMINO- CAPROLACTAMA FSJ-3-amino-caprolactam hydrochloride (2 mmol) and Na2CO3 (6 mmol) in water (20 mL) were added to a solution of octadecanesulfonyl chloride (2 mmol) in dichloromethane (20 mL) at room temperature, and the reaction was stirred for 10 hours. The organic layer was then separated and the aqueous phase was extracted with additional dichloromethane (2 x 25 mL). The combined organic layers were dried over Na2CO3 and reduced in vacuo. The residue was purified by column chromatography on silica gel (3: 1 hexanes: EtOAc for 100% EtOAc) and then by recrystallization from heptane to darfSJ-S-ioctadecanesulphonamino-caprolactam (545 mg, 61%); Melting point: 99-100 ° C; vmax (cm "1): 3356, 3249 (NH), 1659 (CO), 1323, 1140 (SO2N); dH (500 MHz, CDCl 3) 6.15 (1H, t, J 6, CH 2 NH), 5.69 (1H, d , J 6, CHNH), 4.12 (1H, ddd, J 11.5, 6, 2, CHNH), 3.30-3.18 (2H, m, CH2NH), 2.97-2.92 (2H, m, CH2SO2), 2.12-2.07 (1H , m, CH ring), 2.06-1.97 (1H, m, CH ring), 1.87-1.56 (5H, m, CH2CH2SO2 + 3 CH ring), 1.42-1.32 (3H, m, CH + CH2 chain ring), 1.32 -1 .18 (28H, m, CH2 chain) and 0.86 (3H, m, CH3); m / z (MNa + C24H48N2O3SNa requires 467.3277852) 467. 330047.

EXAMPLE 33: ÍS) -AMlNOCAPROLACTAMA-GLYCIN- (L) -N (BOC) - TRYPTOPHAN: This tripeptide was made into a solid-phase automatic peptide synthesizer using fSJ-aminocaprolactam for the coupling step of the final peptide. Mr (Calc) = 471.5110. Mr observed by mass spectrometry 471.6. Purity (% TIC in molecular ion peak) = 90% EXAMPLE 34: ÍS) -AMINOCAPROLACTAMA- (L) -VALINA-ÍL) - DESAMINOTRIPTÓFANO This tripeptide was made into a solid-phase automatic peptide synthesizer using fSJ-aminocaprolactam for the coupling step of the final peptide. Mr (Calc) = 398.4600. Mr observed by mass spectrometry 398.3. Purity (% TIC in molecular ion peak) = 96% EXAMPLES 35-38 OF USEFUL INTERMEDIATE COMPOUNDS IN THE SYNTHESIS OF THE COMPOUNDS OF THE INVENTION EXAMPLE 35: INTERMEDIATE PRODUCT 2.2-DIMETHYL-DODEC-4- ENOATE OF < ?) - METlLO Butyl lithium (3.8 M, 10 mmol) was added to a solution of diisopropylamine (1.42 mL, 10 mmol) in dry THF at -78 ° C under N2. The reaction was stirred at -78 ° C for 20 minutes and then methyl isobutyrate (1.15 mL, 10 mmol) was added. The reaction was stirred at -78 ° C for one hour, and then (γJ-dec-2-enyl) (2.19g, 10 mmol) was added and the reaction allowed to warm to room temperature for 14 hours. the solvent was removed from the reaction in vacuo, and the residue was partitioned between aqueous buffer for a pH of 2 (0.5 M NaHSO 4 / 0.5 M Na 2 SO 4) (100 mL) and hexane (3 x 100 mL). organic layers were combined over Na2SO4 and the solvent was removed in vacuo to give crude methyl (2,2-dimethyl-dodec-4-enoate (> 90% pure) (2.27 g) as a colorless oil, vmax / cm-1. 1734 (CO); dH (400 MHz, CDCl 3) 5.42 (1H, br dt, J 15, 6.5, CH = CH), 5.30 (1H, dtt, J 15, 7, 1, CH = CH), 3.64 (3H, s, OCH3), 2.18 (2H, dd, J 7, 1, CH2CMe2) , 1.96 (2H, br q, J6.5, CH2CH2CH = CH), 1.35-1.20 (10H, m, (CH2) 5CH3), 1.14 (6H, s, C (CH3) 2), 0.87 (3H, t, J 6.5, CH2CH3); dc (125 MHz, CDCI3) 178.2 (CO), 134.1, 125.2 (HC = CH), 51.5 (OCH3), 43.6 (CH2), 42.6 (Me2CCO), 32.6, 31.8, 29.5, 29.1, 29.0 (CH2), 24.7 (C (CH3) x2), 22.6 (CH2), 14.1 (CH2CH3); m / z (MH + C15H29N2O2 requires 241.2168) 241.2169.

EXAMPLE 36: INTERMEDIATE PRODUCT CHLORIDE OF (E) -2.2- DIMETHYL-DODEC-4-ENOYLENE The complete product of the above reaction was subsequently dissolved in ethanol (50 mL) and added to a solution of NaOH (2.0 g, 50 mmol) in water (25 mL). The mixture was heated under reflux for 6 hours, allowed to cool and the solvents were removed in vacuo. The residue was partitioned between aqueous buffer for a pH of 2 (0.5 M NaHSO 4 / 0.5 M Na 2 SO 4) (100 mL) and diethyl ether (3 x 100 mL). The combined organic layers were dried over Na2SO4 and the ether solvent was removed in vacuo to give crude (? J-2,2-dimethyl-dodec-4-enoic acid (> 90% pure) as a colorless oil. MHz, CDCl 3) 5.46 (1H, br dt, J 15, 6.5, CH = CH), 5.35 (1H, dtt, J 15, 7, 1, CH = CH), 2.22 (2H, dd, J7, 1, CH2CMe2 ), 1.98 (2H, br q, J 6.5, CH2CH2CH = CH), 1.37-1.21 (10H, m, (CH2) 5CH3), 1.17 (6H, s, C (CH3) 2), 0.87 (3H, t, J 6.5, CH2CH3) The crude acid was dissolved in dichloromethane (50 mL) and oxalyl chloride (3 mL) was added along with a drop of DMF The reaction was stirred for 1 hour and the solvent was removed in vacuo give (?) - 2,2-dimethyl-dodec-4-enoyl chloride, which was used all without purification in the next step.

EXAMPLE 37: INTERMEDIATE PRODUCT 2.2.5-TRIMET1L-HEX-4- METHYL ENOATE Butyl lithium (2.9 M, 50 mmol) was added to a solution of diisopropylamine (7.2 mL, 50 mmol) in dry THF (200 mL) at -78 ° C under N2. The reaction was stirred at -78 ° C for 20 minutes and then methyl isobutyrate (5.7 mL, 50 mmol) was added. The reaction was stirred at -78 ° C for 1 hour, and then 3-methyl-but-2-enyl bromide (5.8 mL, 50 mmol) was added and the reaction allowed to warm to room temperature for 14 hours. The solvent was then removed in vacuo, and the residue was partitioned between aqueous buffer with pH2 (0.5 M NaHSO4 / 0.5 M Na2SO4) and hexane (3 x 250 mL). The combined organic layers were dried over Na2SO4 and the hexane solvent was removed in vacuo to give methyl 2,2,5-trimethyl-hex-4-enoate as a colorless oil (6.93 g, 81%).; vmax / cm-1 1732 (CO); dH (400 MHz, CDCl 3) 5.04 (1H, tsept, J 7.5, 1.5, CH = C), 3.63 (3H, s, OCH3), 2.20 (2H, d, J 7.5, CHCH2), 1.68 (3H, br s , CH = CMeMe), 1.58 (3H, br s, CH = CMeMe), 1.14 (6H, s, (CH3) 2CO); dc (125 MHz, CDCI3) 178.4 (CO), 134.1 (Me2C = CH), 119.8 (Me2C = CH), 51.6 (OCH3), 42.8 (Me2CCO), 38.7 (CH2), 25.9, 24.7 (x2), 17.8 ( CCH3); m / z (MH + C10H19O2 requires 171.1385) 171.1388.

EXAMPLE 38: INTERMEDIATE PRODUCT CHLORIDE OF 2.2.5- TRIMETHYL-HEX-4-ENOYLENE Methyl 2,2,5-trimethyl-hex-4-enoate (2.74 g, 16 mmol) was dissolved in ethanol (50 mL) and added to a solution of NaOH (3.0 g, 75 mmol) in water (35 g). mL). The mixture was heated under reflux for 6 hours, allowed to cool and the solvents were removed in vacuo. The residue was partitioned between aqueous buffer for a pH of 2 (0.5 M NaHSO 4 / 0.5 M Na 2 SO 4) and diethyl ether (3 x 150 mL). The combined organic layers were dried over Na2SO4 and the ether solvent was removed in vacuo to give 2,2,5-trimethyl-hex-4-enoic acid (> 95% pure) as a colorless oil; dH (400 MHz, CDCl 3) 5.12 (1H, tsept, J 7.5, 1.5, CH = C), 2.25 (2H, d, J 7.5, CHCH2), 1.71 (3H, br s, CH = CMeMe), 1.60 (3H , br s, CH = CMe / We), 1.18 (6H, s, (CH3) 2CO). The crude acid was dissolved in dichloromethane (50 mL) and oxalyl chloride (3 mL) was added along with a drop of DMF. The reaction was stirred for 1 hour and the solvent was removed in vacuo to give 2,2,5-trimethyl-hex-4-enoyl chloride, which was used all without purification in the next step.

EXAMPLE 39: This compound has two head groups on each side of a 2,2,6,6-tetramethyl heptanoic acid. In effect it is a dimer of the corresponding 2,2-dimethyl compound of the invention.

(S.S) N, N'-BIS- (2'-OXO-AZEPAN-3'-IL) 2,2,6,6-TETRAMETILHEPTADI AMIDA Hydro-pyrrolidine-5-carboxylate of (S, S) -3-amino-caprolactam (2 mmol) and Na 2 CO 3 (6 mmol) in water (25 mL) were added to a dichloride solution of 2,2,6,6 -tetramethyl-heptanedioyl (1 mmol) in dichloromethane (25 mL) at room temperature, and the reaction was stirred for 2 hours. The organic layer was then separated and the aqueous phase was extracted with additional dichloromethane (2x 25 mL). The combined organic layers were dried over Na2CO3 and reduced in vacuo. The residue was purified by recrystallization from EtOAc to give the dimer (S.S) - (199 mg, 46%); Melting point: 234-236 ° C; W? (c = 1, CHCl3) +29.4; vmax / cm-1 3379, 3255 (NH), 1683, 1637 (CO), 1507, 1497 (NH); dH (500 MHz, CDCl 3) 7.07 (2H, d, J 5.5, CHNH), 6.42 (2H, br s, CH2NH), 4.44 (2H, ddd, J 11, 5.5, 1.5, CHNH), 3.31-3.17 (4H , m, CH2NH), 2.04-1.94 (4H, m, CH ring), 1.86-1.73 (4H, m, CH ring), 1.51-1.31 (8H, br m, 2x ring CH + CH2CMe2) and 1.12 (14H, m, CH2CH2CH2 + CMe2 chain); dc (125 MHz, CDCl 3) 176.9, 175.9 (CO), 52.1 (NHCH), 42.0 (CMe2), 42.1, 41.5, 31.5, 28.9, 28.0 (CH2), 25.3, 25.1 (CH3) and 20.0 (CH2); m / z (M + C23H40N4O requires 436.30496) 436.30437.

EXAMPLE 40: fS) -3- (1 M '-DIMETILUNDECANOSULFONIDAMINO- CAPROLACTAMA This compound is the sulfonamide analog of Example 12.

EXAMPLE 41: fS) -3- (2'-PROPYLPENTANOIL) AMINO- CAPROLACTMA Hydro-pyrrolidine-5-carboxylate of (S, S) -3-amino-caprolactam (5 mmol) and Na2CO3 (15 mmol) in water (15 mL) were added to a solution of 2-propylpentanoyl chloride (5 mmol) in dichloromethane (15 mL) at room temperature, and the reaction was stirred for 12 hours. The organic layer was then separated and the aqueous phase was extracted with additional dichloromethane (2x 25 mL). The combined organic layers were dried over Na2SO4 and reduced in vacuo. The residue was recrystallized from hexane to give (rSj-3- (2'-propylpentanoyl) amino-caprolactam (1.02 g, 80%); Melting point: (hexanes) 114-118 ° C; M (c = 1 , CHCl3) +29.4; vmax / cm-1 3303 (NH), 1686, 1633 (CO), 1537 (NH); dH (500 MHz, CDCI3) 6.88 (1H, d, J 5.5, CHNH), 6.52 (1H , br s, CH2NH), 4.52 (1H, ddd, J 11, 6, 1.5, CHNH), 3.30-3.16 (2H, m, CH2NH), 2.13-2.02 (2H, m, (CH2) 2CHCO and lactam ring CH ), 2.02-1.92 (1H, m, lactama CH ring), 1.86-1.74 (2H, m, lactam ring CH x2), 1.57-1.50 (2H, m, CH2 side chain), 1.42 (1H, br qd, J 13.5, 3.5, lactam ring CH), 1.38-1.29 (2H, m, lactam ring CH + side chain CH2), 1.29-1.19 (4H, m, side chain CH x4), 0.85 (3H, t, J 7.5, CH3 ) and 0.84 (3H, t, J 7.5, CH3), dc (125 MHz, CDCI3) 175.8, 175.2 (CO), 51.9 (NHCHCO), 47.2 (CH), 42.1, 35.3, 35.1, 31.7, 28.9, 27.9, 20.7 (x2) (CH2) and 14.1 (x2) (CH3); m / z (MH + C14H27N2O2 requires 255.2073) 255.2083.

EXAMPLE 42 (A): (3S, 2'R) AND EXAMPLE 42 (B): (3S, 2'S) -3- (2'- ETHYL-HEXANOIDAMINE-CAPROLACTAMA: Hydro-pyrrolidine-5-carboxylate of (S, S) -3-amino-caprolactam (5 mmol) and Na2CO3 (15 mmol) in water (15 mL) were added to a solution of (+/-) 2- chloride. ethylhexanoyl (5 mmol) in dichloromethane (15 mL) at room temperature, and the reaction was stirred for 12 hours. The organic layer was then separated and the aqueous phase was extracted with additional dichloromethane (2 x 25 mL). The combined organic layers were dried over Na2SO4 and reduced in vacuo. The residue was recrystallized from hexane to give a mixture of (3S, 2'R) and (3S, 2'S) -3- (2'-ethylhexanoyl) amino-caprolactam (328 mg, 26%); vmax / cm-13306 (NH), 1686, 1633 (CO), 1537 (NH); dH (500 MHz, CDCl 3) 6.89 (2 H, d, J 5, CHNH, both isomers), 6.53 (2 H, br s, CH 2 NH, both isomers), 4.52 (2 H, ddd, J 11, 6, 1.5, CHNH, both isomers), 3.30-3.16 (4H, m, CH2NH, both isomers), 2.06 (2H, br d, J 13.5, lactam CH x2, both isomers), 2.02-1.92 (4H, m, (CH2) 2CHCO x2 and ring lactam CH x2, both isomers), 1.86-1.74 (4H, m, lactam ring CH x4, both isomers), 1.63-1.50 (4H, m, CH2 side chain), 1.50-1.30 (8H, m, lactam ring CH x4 + side chain CH2 x4, both isomers), 1.30-1.14 (8H, m, side chain CH2 x8, both isomers), 0.85 (3H, t, J 7.5, CH3, one isomer) and 0.82 (3H, t, J 7.5 , CH3, an isomer); dc (125 MHz, CDCI3) 175.8, 175.1 (CO), 52.0, 51.9 (NHCHCO), 49.3 (x2) (CH), 42.0 (x2), 32.5, 32.3, 31.7 (x2), 29.7 (x2), 28.8 ( x2), 27.9 (x2), 26.1, 25.9, 22.7 (x2), 14.0, 13.9 (CH3) and 12.0 (x2) (CH3); m / z (M + C14H26N2O2 requires 254.1994) 254.1995.

EXAMPLE 43: ACID 3.3-DIMETILDODECANOICO (INTERMEDIATE PRODUCT) Cul (2 mmol), trimethylsilyl chloride (24 mmol) and methyl 3,3-dimethylacrylate (20 mmol) in THF (25 mmol) were cooled to -15 ° C, and a solution of nonylmagnesium bromide ( 24 mmol) in THF (80 mL) for one hour. The reaction was allowed to warm to room temperature overnight, and then the reaction was quenched by the addition of saturated aqueous ammonium chloride. The THF was removed in vacuo and the residue partitioned between hexanes and water. The organic layer was reduced in vacuo and the crude methyl 3,3-dimethyldodecanoate dissolved in ethanol (50 mL). KOH (100 mmol) in water (10 mL) was added and the reaction was heated by reflux for 18 hours. The reaction was allowed to cool and the solvent removed in vacuo, and the residue partitioned between hexane and water. The aqueous layer was then acidified to a pH of 2 with aqueous HCl, and extracted with diethyl ether. The ether layer was dried over Na2SO4 and then the solution was reduced in vacuo to give 3,3-dimethyldodecanoic acid as an oil (3.47 g, 76%); vmax / cm "1 1702 (CO); dH (500 MHz, CDCl 3) 11.12 (1 H, br s, OH), 2.21 (2 H, s, CH 2 CO); 1.32-1.20 (16 H, m, (CH 2) 8), 1.00 (6H, s, C (CH3) 2) and 0.87 (3H, t, J 7, CH2CH3); dc (125 MHz, CDCl 3) 179.1 (CO), 45.9, 42.3 (CH2), 33.2 (C (CH3) 2), 31.9, 30.3, 29.6 (x2), 29.3, 27. 1 (x2) (C (CH3) 2), 24.0, 22.6 (CH2) and 14.1 (CH3); m / z (M + C14H28O2 requires 228.2089) 228.2082.

EXAMPLE 44: CHLORIDE OF 3.3-DIMETILDODECANOILO (INTERMEDIATE PRODUCT) 3,3-Dimethyldodecanoic acid (5 mmol) was dissolved in CH 2 Cl 2 (20 mL), oxalyl chloride (1 mL) and dimethyl formamide (1 drop) were added. After 1 hour, the reaction was reduced in vacuo to give 3,3-dimethyldodecanoyl chloride, which was used directly in the synthesis of fSJ-3- (3 ', 3'-dimethyldodecanoyl) amino-caprolactam.

EXAMPLE 45: fS) -3- (3 ', 3'-DIMETLDLDODECANOIL) AMINO-CAPROLACTMA Hydro-pyrrolidine-5-carboxylate of (S, S) -3-amino-caprolactam 2 (5 mmol) and Na 2 CO 3 (15 mmol) were added. mmol) in water (15 mL) was added to a solution of 3,3-dimethyldodecanoyl chloride (5 mmol) in dichloromethane (15 mL) at room temperature, and the reaction was stirred for 12 hours. The organic layer was then separated and the aqueous phase was extracted with additional dichloromethane (2x 25 mL). The combined organic layers were dried over Na2SO4 and reduced in vacuo. The residue was recrystallized from hexane to give (S) -3-, 3, -dimethyldodecanoyl) amino-caprolactam (1.14 g, 68%); Melting point: (hexanes) 123-125 ° C; C * £ (c = 1, CHCl3) +28.6; Vmax / cm "1 3279 (NH), 1646 (CO), 1498 (NH); dH (500 MHz, CDCl 3) 6.81 (1H, d, J 5.5, CHNH), 6.59-6.42 (1H, br m, CH2NH) , 4.50 (1H, ddd, J 11, 6, 1.5, CHNH), 3.30-3.16 (2H, m, CH2NH), 2.08-2.02 (3H, m, CH2CO + lactama CH ring), 2.00-1.90 (1H, m, lactam ring CH), 1.86-1.75 (2H, m, lactam ring CH x2), 1.47-1.31 (2H, br m, lactam ring CH x2), 1.30-1.17 (16H, m, (CH2) 8), 0.89 ( 6H, s, C (CH3) 2) and 0.84 (3H, t, J7, CH2CH3), dc (125 MHz, CDCI3) 175.8, 170.9 (CO), 52.0 (NHCH), 48.4, 42.6, 41.1 (CH2) , 33.3 (CMe2), 31.9, 31.7, 30.4, 29.7, 29.6, 29.3, 29.3, 28.9, 27.9 (CH2), 27.3 (x2) (CH3), 24.1, 22.6 (CH2) and 14.1 (CH3); m / z (M + C2oH38N2O2 requires 338.2933) 338.2928.

EXAMPLE 46: 2-METILDODEC-2-ENOATE OF EMI-ETHYL (INTERMEDIATE PRODUCT) Decanal (5 mmol) and (carbethoxyethylidene) triphenylphosphorane (10 mmol) were dissolved in CH 2 Cl 2 (20 mL) and the reaction mixture was stirred for 18 hours. The solvent was then removed in vacuo and the residue was filtered through a plug of silica gel with the aid of 5% diethyl ether in hexanes. The collected eluent was reduced in vacuo to give 2-methyldodec-2-enoate (? J-ethyl as an oil (1.02 g, 88%); vmax / cm'1 1709 (CO), 1651 (C = C); dH (500 MHz, CDCl 3) 6.73 (1H, tq, J 7.5, 1.5, CH = C), 4.16 (2H, q, J 7, OCH 2), 2.13 (2H, br q, J 7.5, CH 2 CH = C), 1.80 (3H, d, J 1.5, CH3C = CH), 1.45-1.37 (2H, m, CH2 chain), 1.32-1.19 (15H, m, (CH2) 6 + OCH2CH3) and 0.85 (3H, t, J 7 (CH2) 8CH3) dc (125 MHz, CDCl3) 168.3 (CO), 142.4 (CH = C), 127.6 (CH = C), 60.3 (OCH2), 31.8, 29.5, 29.4 (x2), 29.3, 28.6 , 28.5, 22.6 (CH2), 14.3, 14.1 and 12.3 (CH3); m / z (MH + C15H29O2 requires 241.2168) 241.2165.

EXAMPLE 47: ACID < ?) - 2-METILDODEC-2-ENOIC (INTERMEDIATE PRODUCT) 2-Methyldodec-2-enoate of (E) -Et \\ o (1.43 mmol) was dissolved in ethanol (10 mL), and KOH (10 mmol) in water (5 mL) was added. The reaction was heated by reflux for 18 hours and then cooled. The solvent was removed in vacuo and the residue partitioned between water and hexane. The aqueous layer was acidified with aqueous HCl, and extracted with diethyl ether. The diethyl ether layer was dried over Na2SO4 and reduced in vacuo to give (? J-2-methyldodec-2-enoic acid as a solid (308 mg,> 95%); Melting point: 28-31 ° C; dH (400 MHz, CDCI3) 6.91 (1H, tq, J 7.5, 1.5, CH = C), 2.18 (2H, br q, J 7.5, CH2CH = C), 1.82 (3H, d, J 1.5, CH3C = CH), 1.48-1.39 (2H, m, CH2 chain), 1.36-1.19 (12H, m, (CH2) 6) and 0.88 (3H, t, J7, (CH2) 8CH3) (no OH peak observed) .

EXAMPLE 48: CHLORIDE OF?) - 2-METILDODEC-2-ENOYL (INTERMEDIATE PRODUCT) Acid (? -2-methyldodec-2-enoic (1.43 mmol) was dissolved in CH2Cl2 (20 mL), oxalyl chloride (1 mL) and dimethyl formamide (1 drop) were added, after one hour the reaction was reduced in vacuo to give crude (EJ ~ 2-methyldodec-2-enoyl) chloride, which was used directly in the syn- thesis of ('S) - (? &); -3- (2, -metldodec-2, -enoil) amino-caprolactam.

EXAMPLE 49: ÍSl -? L-S-fa'-METILDODEC-S'-ENOIL) AMINO- CAPROLACTAMA Hydro-pyrrolidin-5-carboxylate of (S, S) -3-amino-caprolactam 2 (2 mmol) and Na 2 CO 3 (6 mmol) in water (15 mL) were added to a solution of (? J-2-) chloride. methyldodec-2-enoyl (1.43 mmol) in dichloromethane (15 mL) at room temperature, and the reaction was stirred for 12 hours, then the organic layer was separated and the aqueous phase was extracted with additional dichloromethane (2x 25 mL). The combined organic layers were dried over Na2SO4 and reduced in vacuo.The residue was recrystallized from hexane to give (S) - (E) -Z- (2'-methyldodec-2'-enoyl) amino-caprolactam (297 mg , 65%); Melting point: (hexanes) 99-100 ° C; vmax / cm-13282 (NH), 1656, 1622 (CO and C = C), 1497 (NH); [«? (c = 1, CHCl3) +38.2; dH (500 MHz, CDCl 3) 7.15 (1H, d, J 5.5, NHCH), 6.48-6.35 (2H, m, NHCH 2 + CH = C), 4.54 (1H, ddd, J 11, 5.5, 1.5, NHCH), 3.33-3.17 (2H, m, CH2NH), 2.14-2.05 (3H, m, CH2CH = C + lactama CH ring), 2.02-1.93 (1H, m, lactama CH ring), 1.88-1.77 (5H, m, ring lactam CH x2 + CH3C = CH), 1.47-1.31 (4H, br m, lactam ring CH x2 + CH2 chain), 1.31-1.17 (12H, m, (CH2) 6) and 0.85 (3H, t, J 7, CH2CH3); dc (125 MHz, CDCI3) 175.9, 168.2 (CO), 136.9 (CH = C), 130.2 (CH = C), 52.3 (NHCH), 42.2 (NHCH2), 31.8, 31.6, 29.5, 29.4 (x2), 29.3 , 28.9, 28.7, 28.3, 27.9, 22.6 (CH2), 14.1 and 12.4 (CH3).

EXAMPLE 50 (A): (3S, 2'R) AND EXAMPLE 50 (B): (3S, 2'S) -3- (2'- METILDODECANOIDAMINO-CAPROLACTAMA: S > ) - (E >) -3- (2, -Methyldodec-2, -enoyl) amino-caprolactam (0. 5 mmol) and Pd (OH) 2 (20% on carbon) to methanol (10 mL) and the mixture was stirred for 18 hours at room temperature under an atmosphere of hydrogen. The reaction was then filtered, and the solvent was removed in vacuo to give (3S, 2'R) and (3S, 2'S) -3- (2'-methydiodecanoyl) amino-caprolactam as a solid (160 mg, >; 95%); vmax / cm'1 3313 (NH), 1671, 1636 (CO), 1515 (NH); dH (500 MHz, CDCl 3) 6.91 (2 H, d, J 5.5, CHNH, both isomers), 6.55 (2 H, br s, CH 2 NH, both isomers), 4.57-4.47 (2 H, m, CHNH, both isomers), 3.34 -3.18 (4H, m, CH2NH, both isomers), 2.29-2.14 (2H, CH3CHCO, both isomers), 2.07 (2H, br d, J 13.5, lactam ring CH, both isomers), 2.02-1. 94 (2H, m, lactam CH ring, both isomers), 1.89-1.76 (4H, m, lactam ring CH x2, both isomers), 1.67-1.57 (2H, m, CH chain, both isomers), 1.51-1.33 ( 6H, m, lactam ring CH x2 + side chain CH2, both isomers), 1.32-1.18 (32H, m, (CH2) 8, both isomers), 1.13 (3H, d, J 7, CHCH3, one isomer), 1.11 (3H, d, J 7, CHCH 3, one isomer) and 0.87 (6H, t, J 7.5, CH 3, both isomers); dc (125 MHz, CDCl 3) 175.9 (x2), 175.8 (x2) (CO, both isomers), 52.0, 51.9 (NCH), 42.1 (x2) (NCH2, both isomers), 41.3, 41.2 (CHCH3), 34.5, 34.1, 31.9 (x2), 31.8, 31.7, 29.6 (x6), 29.5 (x2), 29.3 (x2), 28.9 (x2), 28.0, 27.9, 27.4 (x2), 22.6 (x2) (CH2) 17.8, 17.6 and 14.1 (x2) (CH3); m / z (MH + C19H37N2O2 requires 325.2855) 325.2858.

EXAMPLE 51: (4S, 2, S, 3'R) -4-BENCIL-3- (3'-HYDROXY-2B ° METTILDECANOID-OXAZOLIDIN- 2-QNA (INTERMEDIATE PRODUCT) This reaction with aldo was carried out according to the published method (Crimmins, M. T; She, J .; Synlett, 2004, 1371- 1374). FSJ-4-benzyl-3-propionyl-oxazoIidin-2-one (5 mmol) (synthesized according to the method of Evans and co-authors, Tetrahedron Lett., 1987, 28.1123) was dissolved in CH2Cl2 (25 mL ) and the solution was cooled to -20 ° C under an atmosphere of dry nitrogen and TiCl 4 (5.25 mmol) was added. After 15 minutes, diis-propylethylamine (5.5 mmol) was added. After an additional 40 minutes, N-methyl-pyrrolidin-2-one (5.25 mmol) was added. After an additional 10 minutes, decanal (5.5 mmol) was added and the reaction was stirred for 1 hour. Ammonium chloride solution was added and the reaction mixture was washed with regulator for a pH of 2. (0.5 M Na2SO4 / 0.5 M NaHSO4). The organic layer was dried over Na2SO and reduced in vacuo. The crude product was chromatographed on silica gel (10% to 33% ethyl acetate in hexane) to give (4S, 2'S, 3'R) -4-benzyl-3- (3'-hydroxy-2, -met-decanoan) -oxazolidin-2-one as an oil (1.34 g, 69%); vmax / cm-1 1778 (NCO2), 1697 (CON); dH (500 MHz, CDCI3) 7. 35-7.30 (2H, m, meta-Ph), 7.29-7.24 (1H, m, para-Ph), 7.21-7.17 (2H, m, ortho-Ph), 4.69 (1H, ddt, J 9.5, 7.5, 3.5, CHN), 4.21 (1H, t, J9, OCHH), 4.17 (1H, dd, J 9, 3, OCHH), 3.93 (1H, ddd, J 7, 4.5, 3, CHOH), 3.75 (1H, qd, J7, 2.5, CHCH3), 3.24 (1H, dd, J 13.5, 3.5, CHHPh), 2.87 (1H, br s, CHOH), 2.78 (1H, dd, J 13.5, 9.5, CHHPh), 1.56-1.20 (19H, m, (CH2) 8 + CHCH3) and 0.86 (3H, t, J7, CH2CH3); dc (125 MHz, CDCl 3) 177.6 (CCO), 153.0 (OCO), 135.0 (ipso-Ph), 129.4, 129.0 (ortho- + meta-Ph), 127.4 (para-Ph), 71.5 (CHOH), 66.1 ( OCH2), 55.1 (NCH), 42.1 (CHCH3), 37.8, 33.8, 31.9, 29.6 (x3), 29.3, 26.0, 22.7 (CH2), 14.1 and 10.3 (CH3); m / z (MH + C23H36NO4 requires 390.2644) 390.2641.

EXAMPLE 52: (4R, 2'R.3'S) -4-BENClL-3- 3'-HYDROXY-2'-METHYLDECANOIL) -OXAZOLIDIN-2-ONA (INTERMEDIATE PRODUCT) It was converted (rRJ-4-benzyl-3-propionyl-oxazolidin-2-one into (4R, 2, R, 3'S) -4-benzyl-3- (3'-hydroxy-2, -methyldecanoyl) -oxazoIidin-2 -one according to the above procedure.The spectroscopic NMR data are identical, m / z (MH + C23H36NO4 requires 390.2644) 390.2638.

EXAMPLE 53: ACID (2S.3R) -3-HYDROXY-2-METLLDECANOIC (INTERMEDIATE PRODUCT) It was dissolved (4S, 2, S, 3, R) -4-Benzyl-3- (3, -hydroxy-2'-methydacanoyl) -oxazolidin-2-one (1.42 mmol) in THF (10 mL). Water (2 mL), aqueous hydrogen peroxide (8M, 0.5 mmol) was added and LiOH.H2O (3 mmol) was added, and the reaction mixture was stirred for 18 hours. Na 2 SO 3 (10 mmol) was added and the reaction was extracted with ethyl acetate.

The aqueous layer was then acidified with a regulator for a pH of 2 (0.5 M Na2SO4 / 0.5 M NaHSO4), and extracted with diethyl ether. The diethyl ether layer was dried over Na2SO4 and reduced in vacuo to give (2S, 3R) -3-hydroxy-2-methyldecanoic acid; dH (400 MHz, CDCl 3) 3.96-3.89 (1H, m, CHOH), 2.59 (1H, dq, J7, 3, CHCH3), 1.54-1.36 (2H, m, CH2), 1.36-1.22 (14H, m, (CH2) 7) and 1.20 (3H, d, J 7, CHCH3). This material was used directly in the synthesis of (3S, 2 'S, 3' R) -3- (3'-h id roxi -2'- met i id eca n oil) to my non-captaincy ma.

EXAMPLE 54: ACID (2R, 3S) -3-HYDROXY-2-METHYLDECANOIC (INTERMEDIATE PRODUCT) (2R, 3S) -3-Hydroxy-2-methyldecanoic acid was prepared from (4R, 2'R, 3, S) -4-benzyl-3 (3'-hydroxy-2, -methyldecanoyl) -oxazolidin- 2-one according to the previous procedure.

EXAMPLE 55: Í3S.2'S.3'R) -3- (3'-HYDROXY-2'-METHYLDECANOIL) AMINO-CAPROLACTMA (2S, 3R) -3-Hydroxy-2-methyldecanoic acid (1.40 mmol) was dissolved in MeOH (10 mL), and (S) -3-amino-caprolactam hydrochloride (1.50 mmol) and triethylamine (2 mL) were added. mmol). The reaction was cooled to 0 ° C and 4- (4,6-dimethoxy [1, 3,5] triazin-2-yl) -4-methyl-morpholinium chloride (1.40 mmol) was added. The reaction was partitioned between 4 times and then the solvent was removed in vacuo.The residue was partitioned between ethyl acetate and water, the ethyl acetate layer was washed with dilute aqueous HCl and dilute aqueous NaOH, and then dried over Na2SO4. The solvent was removed in vacuo and the residue was recrystallized from ethyl acetate / hexane to give (3S, 2'S, 3 '/?) - 3- (3'-hydroxy-2'-methydecanoyl) aminocaprolactam as a solid (341 mg, 72%) Melting point (hexanes = 88-91 ° C vmax / cm "13313 (NH), 1628 (CO), 1480 (NH); M (C = 0.5, CHCl3) +40.8; dH (500 MHz, CDCl 3) 7.08 (1H, d, J 5.5, NHCH), 6.51 (1H, br s, NHCH 2), 4.57 (1H, ddd, J 11, 6.5, 1, NCH), 3.83 (1H, dt , J 8, 4, CHOH, 3.36-3.21 (2H, m, NCH2), 2.40 (1H, dq, J 7, 3, CHCH3), 2.12- 1.96 (2H, m, lactam CH x2), 1.90-1.76 ( 2H, m, lactam CH x2), 1.55-1.34 (4H, m, lactam CH x2 + chain (CH2), 1.34-1.21 (14H, m (CH2) 7), 1.17 (3H, d, J 7, CHCH3) and 0.88 (3H, t, J 7, CH 2 CH 3) (OH not observed), dc (125 MHz, CDCl 3) 175.8, 175.7 (CO), 72.1 (CHOH), 52.0 (NCH), 44.6 (CHCH3), 42.1 (NCH2 ), 33.4, 31.9, 31.3, 29.6 (x2), 29.5, 29.3, 28.8, 27.9, 26.1, 22.7 (CH2), 14.1 and 11.2 (CH3); m / z (MH + C19H37N2O3 requires 341.2804) 341.2773.

EXAMPLE 56: (3S.2'ft.3'S) -3- (3'-HYDROXY-2'-METHYLDECANOIDAMINE-CAPROLACTMA Acid (2, R, 3S) -3-hydroxy-2-methyldecanoic acid (1.40 mmol), fSJ-3-amino-caprolactam hydrochloride (1.50 mmol), triethylamine (2 mmol) and chloride of 4- ( 4,6-dimethoxy [1,3,5] triazin-2-yl-4-methyl-morphoinium (1.40 mmol), as above, to produce (3S, 2'R, 3'S) -3- (3'- hydroxy-2'-methydacanoyl) amino-caprolactam, which was recrystallized from ethyl acetate / hexane (86 mg, 18%); melting point (hexanes) 118-121 ° C; vma? / cm-13294 (NH ), 1667, 1613 (CO), 1533 (NH); MD (C = 0.5, CHCl3) +14.8; dH (500 MHz, CDCl 3) 7.11 (1H, d, J 6, NHCH), 6.54 (1H, br s, NHCH 2, 4.53 (1H, ddd, J 11, 6.5, 1.5, NCH), 3.87-3.80 (1H, m, CHOH), 3.70 (1H, br s, OH), 3.34-3.20 (2H, m, NCH2), 2.37 (1H, dq, J7, 3, CHCH3), 2.11-1.96 (2H, m, lactam CH x2 ), 1.90-1.76 (2H, m, lactam CH x2), 1.55-1.21 (18H, m, lactam CH x2 + chain (CH2) 8), 1.16 (3H, d, J 7, CHCH3) and 0.88 (3H, t, J 7, CH 2 CH 3), dc (125 MHz, CDCl 3) 175.9, 175.7 (CO), 72.0 (CHOH), 52.1 (NCH), 44.8 (CHCH3), 42.1 (NCH2), 33.7, 31.9, 31.4, 29.6 ( x2), 29.5, 29.3, 28.8, 27.9, 26.0, 22.7 (CH2), 14.1 and 10.7 (CH3); m / z (MH + C19H37N2? 3 requires 341.2804) 341.2803.

EXAMPLE 57: 2.2-DIMETHYL-3-H1DROXY METHYL DECANATE (INTERMEDIATE PRODUCT) Butyl lithium (2.5 M in hexanes, 50 mmol) was added to a solution of diisopropylamine (50 mmol) in dry THF (200 mL) at -78 ° C under an atmosphere of dry nitrogen. The reaction was stirred for 30 minutes and then methylbutyrate (50 mmol) was added. After 45 minutes, decanal (50 mmol) was added and the reaction allowed to warm to room temperature for 18 hours. After addition of saturated aqueous ammonium chloride (10 mL), the solvent was removed from the reaction in vacuo and the residue was partitioned in hexanes and regulator for a pH of 2 (0.5 M Na 2 SO 4 / 0.5 M NaHSO 4). The organic layer was dried over Na2SO4 and the solvent was removed to give methyl 2,2-dimethyl-3-hydroxy decanoate as an oil (9.98g, 77%); dH (400 MHz, CDCl 3) 3.70 (3H, s, OCH 3), 3.69 (1H, dd, J 10, 2, CHOH), 1.68-1.20 (16H, m, (CH 2) ß), 1-19 (3H, s, CCH3), 1.17 (3H, s, CCH3) and 0.88 (3H, t, J 7, CH2CH3) (no OH was observed).

EXAMPLE 58: 2.2-DIMETHYL-3-HYDROXY DECANOIC ACID (INTERMEDIATE PRODUCT) Methyl 2,2-dimethyl-3-hydroxy decanoate (20 mmol) was dissolved in EtOH (80 mL) and a solution of KOH (40 mmol) in water (20 mL) was added. The reaction was heated by reflux for 18 hours, and then allowed to cool. The solvent was removed in vacuo and the residue partitioned between water and diethyl ether. The aqueous layer was then acidified with a pH2 regulator (0.5 M Na2SO4 / 0.5 M NaHSO4) and extracted with diethyl ether. The solution was dried over Na2SO4 and reduced in vacuo to give 2,2-dimethyl-3-hydroxy decanoic acid, which solidified on standing; Melting point: 39-41 ° C; dH (400 MHz, CDCl 3) 3.64 (1H, dd, J 10, 2, CHOH), 1.67-1.12 (22H, m, (CH 2) 8 + C (CH 3) 2) and 0.88 (3H, t, J 7, CH2CH3).

EXAMPLE 59 (A): (3S, 3'R) AND EXAMPLE 59 (B): (3S, 3'S) -3- (3'-HYDROXY-2'.2'-DIMETHYLENECANOIL) AMINO-CAPROLACTMA 2,2-Dimethyl-3-hydroxy decanoic acid (1.77 mmol) and 1-hydroxybenzotriazole monohydrate (1.77 mmol) were dissolved in THF (10 mL). 1- [3- (Dimethylamino) propyl] -3-ethylcarbodiimide hydrochloride (1.77 mmol) was added and the reaction was stirred at room temperature for 4 hours. A solution of hydropyrrolidin-5-carboxylate (S) was added to it., S) -3-amino-caprolactam 2 (2 mmol) and Na 2 CO 3 (6 mmol) in water (15 mL) and the reaction mixture was stirred for 18 hours. The solvent was then removed from the reaction in vacuo and the reaction residue partitioned between water and ethyl acetate. The ethyl acetate layer was washed with buffer for a pH of 2 (0.5 M Na 2 SO 4 / 0.5 M NaHSO 4) and dilute aqueous sodium hydroxide, and then dried over Na 2 SO 4 and reduced in vacuo. The residue was chromatographed on silica gel (25% ethyl acetate in hexanes for 100% ethyl acetate), to give an emulsion of (3S, 3'R) and (3S, 3'S) -3- (3'- hydroxy-2 ', 2, -dimetildecanocanoyl) amino-caprolactams (557 mg, 88%); dH (500 MHz, CDCl 3) 7.28 (1 H, d, J 6, NHCH an isomer), 7.25 (1 H, d, J 6, NHCH, one isomer), 6.62-6.48 (1 H, br m, NHCH 2, both isomers) , 4.53-4.42 (1H, m, NCH, both isomers), 3.77 (1H, br d, J, 6, OH, one isomer), 3.63 (1H, br d, J, 6, OH, one isomer), 3.47 -3.36 (1H, m, CHOH, both isomers), 3.32-3.17 (2H, m, NCH2, both isomers), 2.07-1.92 (2H, m, lactam CH x2, both isomers), 1.87-1.71 (2H, m , lactam CH x2, both isomers), 1.60-1.17 (21H, m, lactam CH x2 + chain (CH2) 8 + CH3, both isomers), 1.14 (3H, s, CCH3, both isomers) and 0.84 (3H, t , J 7, CH 2 CH 3, both isomers); dc (125 MHz, CDCI3) 177.6, 177.2, 175.8 (CO, both isomers), 77.8, 77.4 (CHOH), 52.1 (NCH, both isomers), 45.9, 45.8 (C (CH3) 2), 42.1, 42.0 (NCH2 ), 31.9 (x2) 31.6, 31.3, 30.9, 29.6 (x4), 29.3, 28.8, 27.9, 26.7, 26.6, 22.6 (CH2), 23.7, 23.5, 21.1, 20.4 and 14.1 (CH3); EXAMPLE 60: ACID 2.2-DIMETHYL-3- (TETRAHIDROPIRAN-2-ILOXD- PROPIONIC (INTERMEDIATE PRODUCT) 2,2-Dimethyl-3-hydroxypropionic acid (100 mmol) and 3,4-dihydro-2H-pyran (210 mmol) were dissolved in dichloromethane (50 mL), and para-toluenesulfonic acid (10 mg) was added. and the reaction was stirred at room temperature for 3 hours, then the solvent was removed from the reaction and the residue was dissolved in ethanol (100 mL), a solution of KOH (120 mmol) in water (30 mL) was added, and the reaction was heated under reflux for 18 hours.The solvent was removed from the reaction in vacuo, and the residue was partitioned between water and diethyl ether.The aqueous layer was acidified with buffer for a pH of 2. (0.5 M Na2SO4 0.5 M NaHSO4) and then extracted with diethyl ether, then the diethyl ether layer was dried over Na2SO and the solvent was removed in vacuo to give 2,2-dimethyl-3- (tetrahydropyran-2-yloxy) acid. propionic as an oil (20.0 g,> 95%), dH (400 MHz, CDCI3) 4.62 (1H, t, J 3.5, CHO2), 3.82 (1H, ddd, J 12, 9, 3, ring CH2O), 3.75 (1H, d, J 12, CH2O chain), 3.55-3.46 (1H, m, CH2O ring), 3.40 (1H, d, J 12, CH2O chain), 1.90-1.45 (6H, m, (CH2) 3), 1.25 (3H, s , CH3) and 1.23 (3H, s, CH3).

EXAMPLE 61: rS) - (2'.2'-DIMETHYL-3'-HYDROXY-PROPIONIL) AMINO- CAPROLACTMA 2,2-Dimethyl-3- (tetrahydropyran-2-yloxy) -propionic acid (4.65 mmol), 1-hydroxybenzotriazole monohydrate (4.65 mmol) and carbonyldiimidazole (4.50 mmol) were dissolved in THF (30 mL) and the reflux reaction for 4 hours. After the reaction was cooled to room temperature, a solution of (S, S) -3-amino-caprolazine hydro-pyrrolidine-5-carboxylate 2 (5 mmol) and Na 2 CO 3 (15 mmol) in water ( 30 mL), and the reaction was stirred for 18 hours. The THF was then removed from the reaction by distillation in vacuo and the aqueous layer was extracted with ethyl acetate. The ethyl acetate layer was dried over Na2SO4 and reduced in vacuo.

The residue was dissolved in MeOH, and acetyl chloride (1 mL) was added. The reaction was stirred at room temperature for 18 hours, and then reduced in vacuo to give fSj- (2'-dimethyl-3'-hydroxypropionyl) aminocaprolactam as a solid (854 mg, 83%); Melting point: 97-99 ° C; MD (c = 0.5, CHCl3) +30.0; dH (400 MHz, CDCl 3) 7.24 (1H, d, J 5.0, CHNH), 6.38 (1H, br s, CH 2 NH), 4.49 (1H, dd, J 10, 6, CHNH), 3.54 (1H, d, J 11, CHHOH), 3.49 (1H, d, J 11, CHHOH), 3.33-3.20 (2H, m, CH2NH), 2.03-1.96 (2H, m, 2x CH ring), 1.87-1.72 (2H, m, 2x CH ring), 1.50-1.30 (2H, m, 2x CH ring), 1.20 (3H, s, CH3) and 1.18 (3H, s, CH3); dc (125 MHz, CDCl 3) 177.2, 176.0 (CO), 69.9 (CHOH), 52.1 (NHCHCO), 43.2 (CCO), 41.9 (CH2N), 31.1, 28.8, 27.9 (CH2 lactam), 22.4 and 22.3 (CH3); EXAMPLE 62: (5) -f3'-CHLORO-2 '- (CHLOROMETHYL) -2'- METILPROPIONIDAMINE- CAPROLACTAMA Hydro-pyrrolidine-5-carboxylic acid (S, S) -3-amino-caprolactam 2 (5 mmol) and Na 2 CO 3 (15 mmol) in water (15 mL) were added to a solution of 3,3'-dichloropivaloyl chloride (5 mmol) in dichloromethane (15 mL) at room temperature, and the reaction was stirred for 12 hours. The organic layer was then separated and the aqueous phase was extracted with additional dichloromethane (2x 25 mL). The combined organic layers were dried with Na2SO4 and reduced in vacuo. The residue was recrystallized from hexane to give (S) - (3'-c \ oro-2'- (chloromethyl) -2'-methylpropionyl) amino-caprolactam (973 mg, 69%); Melting point: (hexanes) 95-96 ° C; MS (c = 0.5, CHCl3) +16.4; dH (500 MHz, CDCI3) 7.33 (1H, d, J 5.0, CHNH), 6.82-6.62 (1H, br m, CH2NH), 4.49 (1H, ddd, J 11, 5.5, 1.5, CHNH), 3.78 (1H, d, J 11, CHHCl), 3.74 (1H, d, J 11, CHHCl), 3.69 (1H, d, J 11, CHHCl), 3.66 (1H, d, J 11, CHHCl), 3.29-3.17 (2H, m, CH2NH), 2.05 (1H, br s, J 13.5, CH ring), 2.01- 1.93 (1H, m, CH ring), 1.87-1.71 (2H, m, 2x CH ring) and 1.49-1.31 (5H, m, 2x CH + CH3 ring); dc (125 MHz, CDCI3) 175.4, 170.6 (CO), 52.6 (NHCHCO), 49.1 (CCO), 48.7, 48.6 (CH2CI), 42.1 (CH2N), 31.1, 28.8, 27.9 (CH2 lactam) and 18.9 (CH3) .

PHARMACOLOGICAL STUDY OF THE PRODUCTS OF THE INVENTION INHIBITION OF MUCRATION OF LEUKOCYTES INDUCED BY MCP-1 PRINCIPLE OF THE ASSAY The biological activity of the compounds of the present invention can be demonstrated using any of a wide range of in vitro leukocyte migration functional assays, including, without limitation, Boyden chamber and related transreceptor migration assays, migration assays with agarose and Direct viewing cameras such as the Dunn Chamber. For example, to demonstrate the inhibition of leukocyte migration in response to chemokines (but not to other chemoattractants), the transceptacle micro assay system has been used in 96-well Neuroprobe format (Gaithersburg, MD, United States) . In principle, this test consists of two chambers separated by a porous membrane. The chemoattractant is placed in the lower compartment and the cells are placed in the upper compartment. After incubation for a period at 37 ° C, the cells move towards the chemoattractant, and the amount of cells in the lower compartment is proportional to the chemoattractant activity (relative to a series of controls). This assay can be used with a range of different leukocyte populations. For example, freshly prepared peripheral blood leukocytes can be used. Alternatively, subsets of leukocytes, including polymorphonuclear cells or lymphocytes or monocytes, may be prepared using methods well known to those skilled in the art, such as density gradient centrifugation or magnetic bead separations. Alternatively, immortal cell lines that have been extensively validated as human peripheral blood leukocyte models can be used, including, but not limited to, THP-1 cells as a monocyte model or Jurkat cells as a T cell model without prior treatment. . While a range of conditions for the assay is available to demonstrate the inhibition of leukocyte migration induced by chemokines, a specific example is provided herein.

MATERIALS The trans-receptor migration systems are manufactured by Neuroprobe, Gaithersburg, MD, USA. The plates used are ChemoTx plates (Neuroprobe 101-8), and transparent plates of 30 μL (Neuroprobe MP30). Geys balanced salt solution is purchased at Sigma (Sigma G-9779). Fatty acid-free BSA is purchased from Sigma (Sigma A-8806). MTT, ie, 3- (4,5-dimethylthiazol-2-yl) -2,5-diphenyltetrasolium bromide, is purchased from Sigma (Sigma M-5655). The RPMI-1640 without phenol red is purchased from Sigma (Sigma R-8755). The THP-1 cell line (Collection of European Cell Cultures) was used as a leukocyte cell population.

PROCEDURE OF THE PROOF The following procedure is used to test the compounds of the invention to determine the migration of leukocytes induced by MCP-1: First, the cell suspension to be placed in the upper compartment is prepared. The THP-1 cells are pelleted by centrifugation (770 x g, 4 min), and washed with balanced saline solution of Geys with 1 mg / mL of BSA (GBSS + BSA). This washing is then repeated, and the cells are pelleted again before being suspended in a small volume of GBSS + BSA to count them, for example using a standard hemocytometer. Then the volume of GBSS + BSA is adjusted depending on the amount of cells present, so that the cells have a final density of 4.45 x 106 cells per mL of GBSS + BSA This ensures that there are 100,000 THP-1 cells in each 25 μL of the solution that will be placed in the upper chamber of the plate. To test a single compound for its ability to inhibit migration induced by MCP-1, it is necessary to prepare two batches of cells. The THP-1 cell suspension at 4.45 x 106 cells / mL is divided into two containers. The inhibitor under test is added to a container, at an appropriate final concentration, in an appropriate vehicle (for example at 1 μM in no more than 1% DMSO). To the second vessel is added an equal volume of GBSS + BSA plus vehicle as appropriate (eg, no more than 1% DMSO), to act as a control. Then, the chemoattractant solution to be placed in the lower compartment is prepared. MCP-1 is diluted in GBSS + BSA to give a final concentration of 25 ng / mL. This is divided into two containers, such as cell suspension. The test compound is added to a vessel in the same final concentration as that in which the test suspension was added, after which a further volume of GBS + BSA plus vehicle as appropriate is added to the other vessel ( example, no more than 1% DMSO). Note that the volume of liquid that needs to be added to make the addition of the test compound has to be taken into account, when establishing the final concentration of MCP-1 in the solution for the lower compartment and the final concentration of cells in the the upper compartment. Once the chemoattractant solutions for the lower receptacles and the cell collutions for the upper chambers have been prepared, the vibration chamber must be assembled. Place 29 μL of the appropriate chemoattractant solution in the ingerior receptacle of the chamber. Trials should be performed at least with triplicate determinations for each condition. Once all the lower chambers have been filled, the porous membrane is applied to the chamber according to the manufacturer's instructions. Finally, 25 μL of the appropriate cell solution is applied to each upper chamber. A plastic lid is placed over the entire apparatus to prevent evaporation. The assembled chamber is incubated at 37 ° C, 5% CO2, for 2 hours. A suspension of cells in BSS + BSA is also incubated under identical conditions in a tube: these cells will be used to construct a standard curve to determine the amount of cells that have migrated into the lower chamber under each condition. At the end of the incubation, the liquid cell suspension is gently removed from the lower chamber, and 20 μL of ice-cold EDTA in 20 mM PBS is added to the upper chamber, and the apparatus is incubated at 4 ° C. during 15 minutes. This procedure causes any cells to adhere to the underside of the membrane to fall into the lower chamber. After this incubation, the filter is carefully washed with BBSS + BSA to wash the EDTA off, and then the filter is removed. The number of cells that migrated to the lower chamber under each condition can then be determined by a number of methods, including direct counting, labeling with fluorescent or radioactive labels or by using a vital dye. Typically, we use the MTT vital dye. 3 μL of mother MTT solution is added to each well, and then the plate is incubated at 37 ° C for 1-2 hours, during which time the dehydrogenase enzymes inside the cells convert the soluble MTT into an insoluble blue formazan product. that can be measured quantitatively. In parallel, a standard curve of 8 points is established.

Starting with the amount of cells added to each upper chamber (100,000) and continuing downwards in 2-fold serial dilutions in GBSS + BSA, the cells are added to a plate in 25 μL, with 3 μL of added MTT stock solution. The plate with standard curve is incubated together with the migration plate. At the end of this incubation, the liquid is carefully removed from the lower chambers, taking care not to disturb the precipitated formazan product. After briefly air-drying, 20 μL of DMSO is added to each lower chamber to solubilize the blue dye, and the absorbance at 595 nm is determined using a 96-well plate reader. The absorbance of each receptacle is then interpolated with the standard curve to estimate the number of cells in each lower chamber. Migration stimulated by MCP-2 is determined by subtracting the average number of cells that reached the lower compartment in receptacles where MCP-1 was not added, from the average number of cells that reached the lower compartment where MCP-1 was present in 25 ng / mL. The impact of the test substance is calculated by comparing the migration induced by MCP-1 that occurred in the presence or absence of various concentrations of the test substance. Typically, the inhibition of migration is expressed as a percentage of the total migration induced by MCP-1, which was blocked by the presence of the compound. For most compounds, a dose response plot is constructed by determining the inhibition of indicted migration by MCP-1 occurring in a range of different concentrations of the compound (typically ranging from 1 nM to 1 μM or more in the case of compounds with low activity). The inhibitory activity of each compound is then expressed as the concentration of compound required to reduce migration induced by MCP-1 by 50% (the ED50 concentration).

RESULTS The compounds of examples 1 to 7 and 9 to 34, and 39, 41, 42, 45, 49, 50, 55, 56, 61 and 62 were tested, where they demonstrated to have an ED50 of 100 nM or less in this test.

ENANTIOSELECTIVITY The (S) - and (R) enantiomers of three different members of the aminocaprolactam series were synthesized to determine if the biological activity showed enantioselectivity. The comparison was made between the compounds of examples 1 and 7, between the compounds of examples 10 and 11, and between the compounds of examples 12 and 17. The dose response curves for each of the four compounds of Examples 1, 7, 10 and 11 as inhibitors of migration of THP-1 cells induced by MCP-1 were determined using the transreceptor migration assay and are shown in Figure 1. In both cases, the (S) enantiomer was significantly (10 to 50 times) more active than the (R) enantiomer. Very similar data were obtained using the compounds of Examples 12 and 17, such that the (S) -enantiomer was significantly (10-50 times) more active than the (R) -enantiomer.

IN VIVO ACTIVITY OF THE COMPOUNDS OF THE INVENTION The anti-inflammatory activity of the compounds of the invention was determined in vivo using a model of sub-lethal endotoxemia induced by LPS. Male adult CD-1 mice (n = 6 per group) were previously treated with various agents (vehicle, compounds of the invention or positive control agents such as steroid dexamethasone) by subcutaneous injection 30 minutes before acute inflammatory exposure with 750 μg of bacterial lipopolysaccharide (from E. Coli 01 1: B4; Sigma Catalog # L-4130) by the intraperitoneal route. The vehicle in each case was 0.6% DMSO, 1% carboxymethyl cellulose, or alternatively 1% carboxymethylcellulose alone. For some of the compounds, this formulation results in a finely divided suspension or mixture, instead of a clear solution. Two hours after exposure to LPS, the animals were sacrificed and blood was drawn by cardiac puncture. The level of the pro-inflammatory cytokine TNF-alpha was determined using the Quantikine M ELISA (R & amp; amp; amp;; D Systems) for murine FNT-alpha, and was reported as the mean ± standard error for each group. Mice that did not receive exposure to LPS had low levels of circulating TNF-alpha (typically 10 pg / mL). At 2 hours after exposure to LPS, these had increased by more than 1000 expires to an average of 20,000 pg / mL, which represents a sensitive index of inflammatory activation. Previous treatment with known anti-inflammatory drugs (such as the steroid dexamethasone) reduced the stimulation of TNF-alpha by up to 85-95%, depending on the dose provided. Compounds 7, 9, 10, 12 and 20 were all tested in this model. The five compounds were able to block the stimulation of TNF-alpha to a similar extent to dexamethasone, when provided in an appropriate dose. All five compounds were active to a maximum extent with a dose below 1 mg / kg. In a separate series of experiments, the compounds of the invention were administered to animals as an oral suspension, formulated in the same manner as for subcutaneous dosing experiments, followed one hour later with exposure to LPS exactly as described previously. Compounds 7, 9, 10, 12 and 20 were tested in this model, and all five compounds were able to block the stimulation of TNF-alpha when administered orally at an appropriate dose. All five compounds were active to a maximum extent in a dose below 30 mg / kg.

Claims

1. Use of a compound of the general formula (I) or a salt thereof acceptable for pharmaceutical use, for the preparation of a medicament directed to treat an inflammatory disorder: (0 characterized in that X is -CO-R1 or -SO2-R2, R1 is an alkyl, haloalkyl, alkoxy, haloalkoxy, alkenyl, alkynyl or alkylamino radical having 4 to 20 carbon atoms (for example 5 to 20 carbon atoms) , from 8 to 20 carbon atoms, from 9 to 20 carbon atoms, from 10 to 18 carbon atoms, from 12 to 18 carbon atoms, from 13 to 18 carbon atoms, from 13 to 17 carbon atoms); and R2 is an alkyl radical of 4 to 20 carbon atoms (for example 5 to 20 carbon atoms, 8 to 20 carbon atoms, 9 to 20 carbon atoms, 10 to 18 carbon atoms, 12 to 18 carbon atoms, 13 to 18 carbon atoms, 14 to 18 carbon atoms, and 13 to 17 carbon atoms); and alternatively, R1 and R2 are independently selected from a peptide moiety, having 1 to 4 peptide moieties linked together by the peptides.

2. Use of a compound of the formula (I ') or of a salt thereof acceptable for pharmaceutical use, for the preparation of a medicament directed at treating an inflammatory disorder:

Ql characterized in that X has the same meaning as indicated above. 3. A pharmaceutical composition containing, as an active ingredient, a compound of the formula (I) or a salt thereof acceptable for pharmaceutical use, and at least one excipient and / or carrier acceptable for pharmaceutical use: characterized in that X is -CO-R1 or -SO2-R2, R1 is an alkyl, haloalkyl, alkoxy, haloalkoxy, alkenyl, alkynyl or alkylamino radical having from 4 to 20 carbon atoms (for example from 5 to 20 carbon atoms). carbon, from 8 to 20 carbon atoms, from 9 to 20 carbon atoms, from 1 0 to 1 8 carbon atoms, from 12 to 18 carbon atoms, from 13 to 18 carbon atoms, from 14 to 18 carbon atoms carbon, from 13 to 17 carbon atoms); and R2 is an alkyl radical of 4 to 20 carbon atoms (for example 5 to 20 carbon atoms, 8 to 20 carbon atoms, 9 to 20 carbon atoms, 10 to 18 carbon atoms, 12 to 18 carbon atoms, 13 to 18 carbon atoms, 14 to 18 carbon atoms, and 13 to 17 carbon atoms); or alternatively, R1 and R2 are independently selected from a peptide moiety, having from 1 to 4 peptide moieties linked together by einacious peptides (e.g., a peptide moiety of 1 to 4 amino acid residues). 4. A pharmaceutical acceptable composition containing an active ingredient, a compound of the formula (I ') or a salt thereof acceptable for pharmaceutical use, and at least one excipient and / or an acceptable acceptor for pharmaceutical use:

(P)

5. A compound of the general formula (I): Wherein X is -CO-R1 or -SO2-R2, R1 is an alkyl, haloalkyl, alkoxy, haloalkoxy, alkenyl, alkynyl or alkylamino radical of 4 to 20 carbon atoms (for example 5 to 20 carbon atoms, from 8 to 20 carbon atoms, from 9 to 20 carbon atoms, from 10 to 18 carbon atoms, from 12 to 18 carbon atoms, from 13 to 18 carbon atoms, from 14 to 18 carbon atoms, from 13 to 17 carbon atoms); and R2 is an alkyl radical of 4 to 20 carbon atoms (for example 5 to 20 carbon atoms, 8 to 20 carbon atoms, 9 to 20 carbon atoms, 10 to 18 carbon atoms, 12 to 18 carbon atoms, 13 to 18 carbon atoms, 14 to 18 carbon atoms, and 13 to 17 carbon atoms); or alternatively, R1 and R2 are independently selected from a peptide moiety, having from 1 to 4 peptide moieties linked together by peptide bonds.

6. A compound of the general formula (I '): Q1 characterized in that X has the same meaning as in claim 5.

7. Compounds, compositions and uses of the compounds of the general formula (I) or (T), or their pharmaceutically acceptable salts, according to any preceding claim, further characterized in that the alkyl, haloalkyl, alkoxy, haloalkoxy, alkenyl, alkynyl or alkylamino part of the radical R1 is linear.

8. Compounds, compositions and uses of the compounds of the general formula (I) or (I '), or their pharmaceutically acceptable salts, according to any of claims 1 to 6, further characterized in that the alkyl, haloalkyl part , alkoxy, haloalkoxy, alkenyl, alkynyl or alkylamino of the radical R1 is branched.

9. Compounds, compositions and uses of the compounds of the general formula (I) or (I '), or their pharmaceutically acceptable salts, according to any preceding claim, wherein the alkyl, haloalkyl, alkoxy, haloalkoxy, alkenyl, alkynyl or alkylamino of the radical R1 is linear or branched, but contains a linear chain of at least 8 or at least 10 carbon atoms.

10. Compounds, compositions and uses according to claim 8 or 9, further characterized in that the radical R1 has an alpha-carbon (position 2 in X), which is substituted with one or two of the same or different groups selected from : alkyl, haloalkyl, alkoxy, haloalkoxy, alkenyl, alkynyl and alkylamino radicals.

11. Compounds, compositions and uses according to claim 8, 9 or 10, further characterized in that the radical R1 has an alpha-carbon (position 2 in X) that is di-substituted with the same or with different groups selected from: alkyl, haloalkyl, alkoxy, haloalkoxy, alkenyl, alkynyl and alkylamino radicals.

12. Compounds, compositions and uses according to claim 10 or 11, further characterized in that the alpha-carbon is chiral.

13. Compounds, compositions and uses according to claim 12, further characterized in that the alpha-carbon has sp3 annealed bonds.

14. Compounds, compositions and uses according to claim 12, further characterized in that the alpha-carbon has essentially tetrahedral bond angles.

15. A use according to claim 1 or a pharmaceutical composition according to claim 3, or a compound according to claim 5, further characterized in that the compound is selected from the group consisting of: - (SJ-3- hexadecanoylamino-caprolactam; - (S,) - 3-undecanoila? T? Ino-caprolactam; - SJ-3- (undec-10-enoyl) amino-caprolactam; - (SJ-3- (undec-10-ynyl) amino-caprolactam; -fS -3-dodecanoylamino-caprolactam; - SJ-3-tetradecanoylamino-caprolactam; -fRJ-3-hexadecanoylamino-caprolactam; - (SJ-3- octad eca noi lam i no-ca pro lactama; - (S) - (Z) -3- (hexadec-9-enoyl) amino-caprolactam; - SJ- (Z) -3- (octadec-9-enoyl) amino-caprolactam; -ff?,) - (Z) -3- (octadec-9-enel) amino-caprolactam; - (5) -3- (2 ', 2'-dimethyl-dodecanoyl) amino-caprolactam; -fSJ-3- (decyloxycarbonyl) amino-caprolactam; - (, SJ - (? Y) -3- (dodec-2-enoyl) amino-caprolactam; -fS,) - 3- (dec-9-enylaminocarbonyl) amino-caprolactam; - SJ-S-idecylaminocarboni amino-caprolactam; and its salts acceptable for pharmaceutical use.

16. A use according to claim 1, or a pharmaceutical composition according to claim 3, or a compound according to claim 5, further characterized in that the compound is selected from the group consisting of: - (RJ-3) - (2 ', 2'-D-methyl-dodecanoyl) amino-caprolactam; -fSJ-3- (2', 2'tDimethyl-pentanoyl) amino-caprolactam; - SJ-3- (2 ', 2'-Dimethyl) -pent-4-enoyl) amino-caprolactam; - ('SJ-3- (2', 2'-Dimethyl-propionyl) amino-caprolactam; - S -3- (2 ', 2'-Dimethyl-butyryl) amino -caprolactam; -CS, £ 3- (2 ', 2' -Di meti-dodec-4'-enoyl) at min o-ca pro lactama; -fSJ-3- (2 ', 2', 5'- Trimethyl-hex-4'-enoyl) amino-capro! Actama; - (S) -3- (2 ', 2', 5, -Trimethyl-hexanoyl) amino-caprolactam; - (S) -3- (11 ' -bromo-undecanoyl) amino-caprolactam; - (S) -3- (11'-azido-undecanoyl) amino-caprolactam; -11-Sulfonate hydroxide of sodium (S) -3- (undecanoyl) amino-caprolactam; - (SJ-S-ÍDecanosulfoniOamino-caprolactam; -f S,) - 3- (Dodecanos ulfon ¡l) amino-caprola cta ma, • - (S) -3- (Tet rad eca n or u Ifon i I) am i no-ca pro lactama; - (SJ-S-ΔH-adedecanesulfoni amino-caprolactam; -fSJ-3- (Octadecanesulfonyl) am-no-ca prolactam; and its pharmaceutically acceptable salts

17. A use according to claim 1, or a composition pharmaceutical according to claim 3, or a compound according to claim 5, further characterized in that the compound is selected from the group consisting of: (S) -3- (2 ', 2'-dimethyl-dodecanoyl) amino- caprolactam, SJ-3- (2 ', 2'-dimethyl-propionyl) amine-caprolactam and its pharmaceutically acceptable salts

18. A use according to claim 1 or a pharmaceutical composition according to claim 3 , or a compound according to claim 5, further characterized in that the compound is selected from the group consisting of: - CS /) - 3- (2'-Propyl-pentanoyl) amino-caprolactam; - (3S, 2'R) and (3S, 2'Sj-3- (2'-ethylhexanoyl) amino-ca? Rolac-tama; -fS -3- (3 ', 3'-D-methyldodecanoyl) amino- caprolactam; - (S) - (E) -3- (2'-Meti l dodec-2'-enoi I) to my no-cap rola cta ma; - (3S, 2'R) and (3S, 2 ' SJ-3- (2'-Methyldodecanoyl) amino-caprolactam; - (3S, 2'S, 3'f? J-3- (3'-H, droxy-2'-methyl decacanoyl) amino- caprolactam; - (3S, 2 'R, 3' SJ-3- (3'-H-droxy-2'-methyl decanoyl) aminocaprolactam; (3S, 3'R) and (3S, 3'SJ-3 - (3'-Hydroxy-2 ', 2'-dimethyl-decanoyl) amino-caprolactam; - SJ- (2', 2-Dimethyl-3, -hydroxy-propionyl) amino-caprolactam; -CSJ- (3 , Chloro-2 '- (chloromethyl) -2, -methylpropionyl) amino-caprolactam and its pharmaceutically acceptable salts

19. Use of a compound of the formula (I) or (I') in accordance with any of claims 1, 2, 15, 16, 17 and 18 further characterized because the inflammatory disorder is selected from the group consisting of autoimmune diseases, vascular disorders, infection or viral replication, asthma, osteorporosis (low density of my bones), tumor growth, rheumatoid arthritis, rejection of organ transplants and / or graft or delayed organ function, a disorder characterized by a high level of TNF-a, psoriasis, skin wounds, disorders caused by parasites intracellular, allergies, Alzheimer's disease, antigen-induced rejection response, suppression of immune response, multiple sclerosis, ALS, fibrosis, and adhesion formation.

20. A method for the treatment, amelioration or prophylaxis of the symptoms of an inflammatory disease (including an adverse inflammatory reaction to any agent) by administering to a patient an anti-inflammatory amount of a joint., composition or medicament as described in any of claims 1 to 1 8.

21. Compounds, compositions and uses of the compounds of the general formula (I) or (I '), or their pharmaceutically acceptable salts, or a method of treatment according to any preceding claim, except claim 7, further characterized in that the Substituent R1 is not a straight chain alkyl group.

22. Compounds, compositions and uses of the compounds of the general formula (I) or (I '), or their pharmaceutically acceptable salts, or a method of treatment according to any preceding claim, except claim 7, further characterized because the substituent R is a branched chain alkyl group.

23. Compounds, compositions and uses of the compounds of the general formula (I) or (I '), or their pharmaceutically acceptable salts, or a method of treatment according to any preceding claim, further characterized in that the substituent R1 is not it is an alkyl group.

24. A pharmaceutical composition for the treatment of an inflammatory disorder containing, as an active ingredient, (S, SJ? /,? '-bis- (2, -oxo-azepan-3'-i 1) 2,2, 6 , 6-tetramethylheptadiamide, or a salt thereof acceptable for pharmaceutical use, and at least one excipient and / or carrier acceptable for pharmaceutical use.

25. A synthetic intermediate useful in the synthesis of compounds of the general formula (I) or (I '), selected from the group consisting of: - 2,2-dimethyl-dodec-4-enoate of (E) -methi \or; - (?) - 2,2-dimethyl-dodec-4-enoyl chloride; - Methyl 2,2,5-trimethyl-hex-4-enoate; - 2,2,5-trimethyl-hex-4-enoyl chloride; - 3,3-dimethyldodecanoic acid; - 3, 3-D-imethyldodecanoyl chloride; - 2-methyldodec-2-enoate of (E) -Et \ o; - (£,) - 2-Methododec-2-enoic acid; - (? J-2-Methyldodec-2-enoyl chloride; -f4S, 2'S, 3'R; -4-Benzyl-3- (3, -hydroxy-2'-methydecanoyl) -oxazolidin-2-one; - (4R, 2'R, 3'S; -4-Benzyl-3- (3, -hydroxy-2'-methyldecanoyl) -oxazolidin-2-one; - (2S, 3? J-3) acid Hydroxy-2-methoxydecanoic acid - (2R, 3S-3-Hydroxy-2-methyldecanoic acid - 2,2-dimethyl-3-hydroxy decanoate - 2,2-Dimethyl-3-hydroxy decanoic acid - 2,2-Dimethyl-3- (tetrahydropyran-2-yloxy) -propionic acid and its pharmaceutically acceptable salts

26. A use according to claim 1, or a pharmaceutical composition according to claim 3 , or a compound according to claim 5, further characterized in that the compound is fSJ-S-1'-1'-dimethylundecanosulfoniOamino-caprolactam or a salt thereof acceptable for pharmaceutical use.