MX2008008670A

MX2008008670A - 1,3-dioxane carboxylic acids

Info

Publication number: MX2008008670A
Application number: MXMX/A/2008/008670A
Authority: MX
Inventors: Braj Bhushan Lohray; Vidya Bhushan Lohray; Harikishore Pingali; Pankaj Ramanbhai Patel; Pankaj Maganlal Makadia
Original assignee: Cadila Healthcare Limited; Braj Bhushan Lohray; Vidya Bhushan Lohray; Pankaj Maganlal Makadia; Pankaj Ramanbhai Patel; Harikishore Pingali
Priority date: 2006-02-27
Filing date: 2008-07-02
Publication date: 2008-09-26

Abstract

The present invention relates to novel 1,3-dioxane carboxylic acids of the general formula (I), their tautomeric forms, their stereoisomers, their pharmaceutically acceptable salts, pharmaceutical compositions containing them, methods for their preparation, use of these compounds in medicine and the intermediates involved in their preparation.

Description

LE.

CIDOS 1, 3-DIOXANCARBOXILICOS FIELD OF THE INVENTION The present invention relates to novel 1,3-dioxancarboxylic acids of general formula (I), their tautomeric forms, their stereoisomers, their pharmaceutically acceptable salts, the pharmaceutical compositions containing them, the methods for their preparation, the use of these compounds in medicine and the intermediates used in their preparation.

The compounds of general formula (I) lower blood glucose, lower or regulate triglyceride levels and / or cholesterol and / or low density lipoprotein (LDL) levels and increase plasma levels of high density lipoproteins (HDL) and therefore they are useful to combat different ailments, in which these reductions (and increases) are beneficial. So they could be used in the treatment and / or prophylaxis of obesity, hyperlipidemia, hypercholesterolemia, hypertension, atherosclerotic diseases, vascular restenosis, 52. 517 diabetes and many other related conditions. The compounds of general formula (I) are useful for preventing or reducing the risk of developing atherosclerosis, which leads to diseases and conditions such as arteriosclerotic diseases, cardiovascular diseases, cerebrovascular accidents, coronary diseases, cerebrovascular diseases, peripheral vessel diseases and related disorders. . These compounds of general formula (I) are useful for the treatment and / or prophylaxis of vaguely defined metabolic disorders such as syndrome X. The characteristics of syndrome X include the initial resistance to insulin followed by hyperinsulinemia, dyslipidemia and glucose intolerance. The glucose intolerance can lead to non-insulin-dependent diabetes mellitus (NIDDM, type 2 diabetes), which is characterized by hypergiukaemia, which if not controlled can lead to diabetic complications or metabolic disorders caused by insulin resistance. Diabetes is no longer considered associated only with glucose metabolism, but also affects anatomical and physiological parameters, whose intensity varies depending on the stages and / or duration and severity of diabetes status. The compounds of this invention have 52. 517 are useful for preventing, stopping or reducing the progress or risk of the above-mentioned disorders and the resulting secondary diseases such as cardiovascular diseases, such as arteriosclerosis, atherosclerosis; diabetic retinopathy, diabetic neuropathy and renopathies that include diabetic neuropathy, glomerulonephritis, glomerular sclerosis, nephrotic syndrome, hypertensive nephrosclerosis and terminal renal diseases, such as microalbuminuria and albuminuria, which can be derived from hypergiucemia or hyperinsulinemia. The compounds of the present invention may be useful as inhibitors of aldose reductase; to improve cognitive functions in dementia and in the treatment and / or prophylaxis of disorders such as psoriasis, polycystic ovary syndrome (PCOS), cancer, osteoporosis, leptin resistance, inflammation and inflammatory bowel disease, xanthoma, pancreatitis, myotonic dystrophy , endothelial cell dysfunction and hyperlipidemia.

BACKGROUND OF THE INVENTION Hyperlipidemia has been identified as the main risk factor in cardiovascular disease derived from atherosclerosis. Atherosclerosis and other peripheral vascular diseases affect the quality of 52. 517 life of a large population in the world. The therapy is aimed at lowering high plasma LDL cholesterol, low density lipoprotein and plasma triglycerides, in order to prevent or reduce the risk of cardiovascular diseases. The detailed etiology of atherosclerosis and coronary artery disease is analyzed by Ross and Glomset [New Engl. J. Med., 295, 369-377 (1976)]. Plasma cholesterol is found, usually, esterified with several serum lipoproteins and several studies suggest that there is an inverse relationship between the level of serum HDL cholesterol and the risk of cardiovascular disease. Many studies suggest that the risk of coronary artery disease (CAD) is greater due to elevated levels of LDL and VLDL cholesterol [Stampfer et al., N. Engl. J. Med., 325, 373-381 (1991)]. The other studies illustrate protective effects of HDL against the progression of atherosclerosis. In this way, HDL has become a crucial factor in the treatment of diseases that present high cholesterol levels [Miller et. al., Br. Med. J. 282, 1741-1744 (1981); Picardo et al., Arteriesclerosis, 6, 434-441 (1986); Macikinnon et al., J. Biol. Chem. 261, 2548-2552 (1986)]. Diabetes is associated with several complications and also affects a large population. This disease by 52. 517 is usually associated with other diseases such as obesity, hyperlipidemia, hypertension and angina. It is well established that inadequate treatment can aggravate glucose intolerance and insulin resistance, and lead to overt diabetes. On the other hand, patients with insulin resistance and type 2 diabetes often have high triglycerides and low concentrations of HDL cholesterol and therefore have a higher risk of cardiovascular disease. Current therapy for these diseases includes sulfonylureas and biguanides along with insulin. This type of pharmacological therapy can give rise to mild to severe hypoglycemia, which in turn can lead to coma or in some cases to death, as a result of unsatisfactory glycemic control by these medications. Recently other drugs have been added in the treatment of diabetes and are thiazolidinediones, drugs that have an action of sensitization to insulin. Thiazolidinediones such as troglitazone, rosiglitazone, and pioglitazone are prescribed alone or in combination with other antidiabetics. These are useful in the treatment of diabetes, and lipid metabolism, but are suspected to have the potential to induce tumors and cause liver dysfunction that can lead to liver failure. By 52. On the other hand, there have been serious undesirable side effects in studies with animals and / or people, including cardiac hypertrophy, hemodilution and hepatotoxicity in some glitazones in ongoing studies with people. The disadvantage is considered idiosyncratic. At present, there is a need for a safe and effective medication to treat insulin resistance, diabetes and hyperlipidemia. [Exp. Clin. Endocrinol Diabetes: 109 (4), S548-9 (2001)]. Obesity is another important health problem that is associated with higher morbidity and mortality. It is a metabolic disorder in which an excess of fat accumulates in the body. Although its etiology is unclear, in general terms, a caloric intake exceeding consumption is included. To combat obesity, several therapies have been used, such as diet, exercise, suppression of appetite, inhibition of fat absorption, etc. However, it is very important that there are more effective therapies to treat this disorder since obesity is closely related to several diseases such as coronary heart disease, stroke, diabetes, intestinal disease, osteoarthritis, hyperlipidemia and lower fertility. It also gives rise to social and psychological problems [Nature Reviews: Drug Discovery: 1 (4), 276-86 (2002)]. 52. 517 Peroxisome Proliferator Activated Receptor (PPAR) is a member of the family of steroid / retinoid / thyroid hormone receptors. The PPARoc, PPAR? and PPARd have been identified as subtypes of PPAR. There are numerous publications of comprehensive reviews on PPAR and its role in different clinical settings [Endocrine Reviews, 20 (5), 649-688 (1999); J. Medicinal Chemistry, 43 (4), 58-550 (2000); Cell, 55, 932-943 (1999); Na ture, 405, 421-424 (2000); Trends in Pharmacological Sci. , 469-473 (2000)]. It has been found that the activation of PPAR? it plays an essential role in the initiation and regulation of adipocyte differentiation [Endocrinology 135, 798-800, (1994)] and homeostatic energy, [Cell, 83, 803-812 (1995); Cell, 99, 239-242 (1999)]. The PPAR agonists? they would stimulate the terminal differentiation of the adipocyte precursors and cause morphological and molecular changes characteristic of a more differentiated, less malignant state. During the differentiation of adipocytes, several highly specialized proteins are induced, which participate in the storage and metabolism of lipids. It is admitted that the activation of PPAR? leads to expression of the CAP gene [Cell Biology, 95, 14751-14756, (1998)], however, the exact link of PPAR activation? for changes in glucose metabolism and the 52. 517 decrease in insulin resistance in muscles, has not been clarified. PPARa participates in the stimulation of ß-oxidation of fatty acids [Trends Endocrine. Metabolism, 4, 291-296 (1993)] which results in the reduction of circulating plasma fatty acids [Current Biol. , 5, 618-621 (1995)].

Recently, the activation function of PPAR? in the terminal differentiation of adipocyte precursors has been implicated in the treatment of cancer. [Cell, 79, 1147-1156 (1994); Cell, 377-389 (1996); Molecular Cell, 465-470 (1998); Carcinogenesis, 1949-1953 (1998); Proc. Na ti. Acad. Sci. , 94, 237-241 (1997); Cancer Research, 58, 3344-3352 (1998)]. Since the PPAR? is expressed in certain cells in a consistent manner, the PPAR agonists? would result in a non-toxic chemotherapy. There is growing evidence that PPAR agonists can also influence the cardiovascular system through the PPAR receptors and also directly by modulating the function of the vascular wall [Med. Res. Rev., 20 (5), 350-366 (2000)]. It has been found that PPAR agonists are useful in the treatment of obesity (WO 97/36579). It has been suggested that the double agonists of PPAR a and? they are useful in syndrome X (WO 97/25042). It has been observed that the PPAR agonists? and the HMG-CoA inhibitors 52. 517 reductase exhibit synergy and have shown the utility of the combination in the treatment of atherosclerosis and xanthoma (EP 0753298). Leptin is a protein that, when it binds to leptin receptors, participates in the delivery of the satiety signal to the hypothalamus. Therefore, resistance to leptin would result in excessive food intake, reduced energy expenditure, obesity, glucose intolerance and diabetes [Science, 269, 543-46 (1995)]. It has been reported that insulin sensitizers decrease the plasma concentration of leptin [Proc. Na ti. Acad. Sci. 93, 5793-5796 (1996): WO 98/02159)]. Several compounds that are double PPAR a and γ agonists have been reported. such as the alkoxy phenylpropanoic acid derivatives, the aryloxypropanoic acid derivatives, the benzyl glycine derivatives, etc. and they are in various stages of development. U.S. Patent No. 20030166697 (Nippon Shinayaku) discloses compounds with the following general formula: wherein 52. 517 Ri represents (un) substituted aryl, aromatic heterocyclic or cycloalkyl groups; and Het 'is an optionally substituted divalent aromatic heterocyclic group; W is -CH- or N; m = 1-10; n = 0-9; p = 0-2; Y = O or S; R3 is H or alkyl; Z = carboxyl, alkoxy carbonyl, etc. WO 2000004011 discloses compounds with the following general formula for the treatment of dyslipidemia, atherosclerosis and diabetes; wherein X, Y = CH2, O, S, NRa (Ra = H, alkyl, aryl, etc.); R = H, alkyl, cycloalkyl, etc .; R1 = H, alkyl, hydroxyalkyl, - (CH2) t-COORc where t = 0-6 and Rc represents H or an alkyl group, etc .; R2 and R3 = H, alkyl, cycloalkyl, (Cd-Cio) aryl, (Cd-Cio) aryl (C? -C) alkyl, an optionally substituted 3-10 membered heterocyclic group, etc .; or R2 and R3 optionally form a chain - (CH2) n (rI = 2-5), etc .; R4-R7 = H, alkyl, aryl 52. 517 (not) substituted, etc. However, the therapeutic potential of these compounds for the treatment of diseases has not yet been proven and the need continues to develop new drugs that are better or their efficacy comparable to that of the current treatment schemes, have fewer side effects and require a regimen of treatment. lower dosage. We hereby present new compounds of formula (I) which are useful as hypocholesterolemic, hypolipidemic, hypolipoproteinemic, anti-obesity and antihyperglycemic agents and can also have a body weight reducing effect and a beneficial effect in the treatment and / or prophylaxis of diseases caused by hyperlipidemia, diseases classified as part of syndrome X and atherosclerosis, and methods for their preparation are also exposed.

PREFERRED MODALITIES OF THE INVENTION The main objective of the present invention is to provide novel substituted 1,3-dioxancarboxylic acids and their derivatives represented by the general formula (I), their tautomeric forms, their stereoisomers, their pharmaceutically acceptable salts, and the pharmaceutical compositions that contain them or the mixtures of 52. 517 same. In one embodiment of the present invention, a process for the preparation of new substituted 1,3-dioxancarboxylic acid acids and their derivatives represented by the general formula (I), their tautomeric forms, their stereoisomers, their pharmaceutically acceptable salts is presented. In another embodiment of the present invention there are presented pharmaceutical compounds of compounds of general formula (I), their tautomeric forms, their stereoisomers, their pharmaceutically acceptable salts, or their mixtures in combination with vehicles, solvents, suitable diluents and other means of common use. in the preparation of this type of compositions.

DETAILED DESCRIPTION OF THE INVENTION Therefore, the present invention relates to compounds of general formula (I), its tautomeric forms, its stereoisomers, its pharmaceutically acceptable salts, and the pharmaceutical compositions containing them, wherein 52. 517? A 'represents an optionally substituted fused or unfused group selected from aryl, heteroaryl, heterocyclyl groups; ? B 'represents a substituted or unsubstituted linear or branched (C? -C6) alkyl group; ? m 'represents an integer of 2-6; Ri represents a group (C1-C3) alkyl, R2 represents hydrogen, linear or branched alkyl (C1-C3) alkyl group. The aryl group may be an aromatic system containing one, two or three rings wherein the three rings may be linked together without fusing or may be fused; in a preferred embodiment the aryl group can be selected from phenyl, naphthyl, tetrahydronaphthyl, indane, biphenyl; The heteroaryl group represents aromatic radicals of 5 to 8 members, which may be simple or fused and which contain one or more heteroatoms selected from 0, N or S; in a preferred embodiment these groups may be selected from pyridyl, thienyl, furyl, pyrrolyl, oxazolyl, thiazolyl, isothiazolyl, imidazolyl, isoxazolyl, oxadiazolyl, thiadiazolyl, triazolyl, tetrazolyl, benzopyranyl, benzopyranonyl, benzofuranyl, benzothienyl, indolinyl, indolyl, azaindolyl groups. , azaindolinyl, benzodihydrofuranyl, 52. 517 benzodihidrotienilo, pyrazolopyrimidinyl, pirazolopirimidonilo, azaquinazolinyl, azaquinazolinoilo, pyridofuranyl, pyridothienyl, thienopyrimidyl, tienopirimidonilo, quinolinyl, pyrimidinyl, pyrazolyl, quinazolinyl, quinazolonilo, pyrimidonyl, pyridazinyl, triazinyl, benzoxazinyl, benzoxazinonyl, benzothiazinyl, benzotiazinonilo, benzoxazolyl, benzothiazolyl, benzimidazolyl, benzotriazolyl , phthalazinyl, naphthylidinyl, purinyl, carbazolyl, phenothiazinyl, phenoxazinyl; The term "heterocyclyl" represents saturated, partially saturated and unsaturated ring-shaped radicals with heteroatoms selected from nitrogen, sulfur and oxygen; in a preferred embodiment these groups may be selected from pyrrolidinyl, imidazolidinyl, piperidinyl, piperazinyl, morpholinyl, oxazolidinyl, thiazolidinyl groups, and the like; Examples of partially saturated heterocyclic radicals include dihydrothiophene, dihydropyran, dihydrofuran, dihydrothiazole groups; When A is substituted, the substituents may be selected from hydroxyl, oxo, halo, thio, amino, or substituted or unsubstituted groups selected from alkyl, haloalkyl, aminoalkyl, alkoxy, alkoxyalkyl, haloalkoxy, cycloalkyl, alkoxy, 52. 517 cycloalkoxy, aryl, aryloxy, aralkyl, aralkoxy, heteroaryl, heteroaralkyl, heteroaryloxy, acyl, acyloxy, hydroxyalkyl, alkoxyalkyl, aryloxyalkyl, aralkoxyalkyl, alkylthio, thioalkyl, aminocarbonyl, arylthio, alkylsulfonyloxy, sulfenyl derivatives, sulfonyl derivatives. When the substituents of are also substituted, these substituents are selected from hydroxyl, oxo, halo, thio, or substituted or unsubstituted groups selected from alkyl, haloalkyl, alkoxy, haloalkoxy, acyl, acyloxy, alkylthio, thioalkyl, alkylsulfonyloxy, alkoxycarbonylamino, derivatives sulfenyl, sulfonyl derivatives. The various groups, radicals and substituents used in any part of the specification are described in the following paragraphs. In another preferred embodiment the groups, radicals described above, can be selected from: the "alkyl" group used alone or in combination with other radicals, represents a straight or branched radical having from one to six carbon atoms and select from methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, tert-butyl, amyl, t-amyl, n-pentyl, n-hexyl, n-heptyl, iso-heptyl, n- octyl, iso-octyl and the like; 52. 517 - the "cycloalkyl" or "alicyclic" group used alone or in combination with other radicals, is selected from a cyclic radical having from three to six carbon atoms, more preferably, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and the like; the term "bicycloalkyl" refers to more than one cycloalkyl group fused together; - the group "alkoxy" used alone or in combination with other radicals, is selected from groups containing an alkyl radical, as defined above, directly attached to an oxygen atom, more preferably, groups selected from methoxy, ethoxy, n-propoxy, iso-propoxy, n-butoxy, t-butoxy, iso-butoxy, pentyloxy, hexyloxy, and the like; - the group "haloalkyl" is selected from an alkyl radical, as defined above, suitably substituted with one or more halogens; as perhaloalkyl, more preferably perfluoro (Ci-Cβ) alkyl such as fluoromethyl, difluoromethyl, trifluoromethyl, fluoroethyl, difluoroethyl, trifluoroethyl, methyl, ethyl, propyl, butyl, pentyl or hexyl groups, mono or polyhalo substituted; - the group "haloalkoxy" is selected from a suitable haloalkyl, as defined above, directly attached to an oxygen atom, 52. 517 more preferably, groups selected from fluoromethoxy, chloromethoxy, fluoroethoxy, chloroethoxy and the like; - the "aryl" or "aromatic" group used alone or in combination with other radicals, is selected from a suitable aromatic system containing one, two or more rings and wherein these rings may be linked together without fusing or may be fused, more preferably, the groups are selected from phenyl, naphthyl, tetrahydronaphthyl, indane, biphenyl, and the like; the "heterocyclyl" or "heterocyclic" group used alone or in combination with other radicals, is selected from mono-, bi- or tricyclic aromatic or non-aromatic saturated, partially saturated or unsaturated radicals, which contain one or more heteroatoms selected from nitrogen, sulfur and oxygen, more preferably, selected from aziridinyl, azetidinyl, pyrrolidinyl, imidazolidinyl, piperidinyl, piperazinyl, 2-oxopiperidinyl, 4-oxopiperidinyl, 2-oxopiperazinyl, 3-oxopiperazinyl, morpholinyl, thiomorpholinyl, 2-oxomorpholinyl, azepinyl, diazepinyl, oxapinilo, thiazepinyl, oxazolidinyl, thiazolidinyl, dihydrothiophene, dihydropyran, dihydrofuran, dihydrothiazole, benzopyranyl, benzopyranonyl, benzodihidrofuranilo, benzodihidrotienilo, pirazolopirimidonilo, azaquinazolinoilo, tienopirimidonilo, quinazolonilo, pyrimidonyl, benzoxazinyl, benzoxazinonyl, benzothiazinyl, benzotiazinonilo, thieno piperidinyl, and the like; the "heteroaryl" or "heteroaromatic" group used alone or in combination with other radicals, is selected from suitable simple or fused aromatic, mono, bi or tricyclic heterocyclic radicals, containing one or more heteroatoms selected from 0, N or S, more preferably, the groups are selected from pyridyl, thienyl, furyl, pyrrolyl, oxazolyl, thiazolyl, isothiazolyl, imidazolyl, isoxazolyl, oxadiazolyl, thiadiazolyl, triazolyl, tetrazolyl, benzofuranyl, benzothienyl, indolinyl, indolyl, azaindolyl, azaindolinyl, pyrazolopyrimidinyl , azaquinazolinyl, pyridofuranyl, pyridothienyl, thienopyrimidyl, quinolinyl, pyrimidinyl, pyrazolyl, quinazolinyl, pyridazinyl, triazinyl, benzimidazolyl, benzotriazolyl, phthalazinyl, naphthylidinyl, purinyl, carbazolyl, phenothiazinyl, phenoxazinyl, benzoxazolyl, benzothiazolyl and the like; the groups "heteroaryloxy", "heteroaralkoxy", "heterocycloxy", "heterocyclylalkoxy" are selected from suitable groups heteroaryl, heteroarylalkyl, heterocyclyl, heterocylalylalkyl, respectively, as defined above, attached to an oxygen atom; the term "aralkyl" refers to an aryl group as defined above, directly attached to an alkyl group as defined above, in one or more positions; the term "aralkoxy" refers to an aralkyl group, as defined above, directly attached to an oxygen atom; - the terms "cycloalkoxy" and "aryloxy" refer to a cycloalkyl group and an aryl group respectively, as defined in the foregoing, attached directly to an oxygen atom; herein, the term "heteroaralkyl" used alone or in combination with other radicals, denotes a heteroaryl group, as defined above, attached to a saturated, straight or branched chain containing 1 to 6 carbon atoms, such as (2) -furyl) methyl, (3-furyl) methyl, (2-thienyl) methyl, (3-thienyl) methyl, (2-pyridyl) methyl, 1-methyl-1- (2-pyrimidyl) ethyl and the like; herein, the term "aryloxyalkyl" used alone or in combination with other radicals, includes phenoxymethyl, naphthyloxymethyl, and the like; herein, the term "aralkoxyalkyl" used alone or in combination with other radicals, includes C6H5CH2OCH2, C6H5CH2OCH2CH2, and the like; herein, the term "arylthio" used alone or in combination with other radicals, refers to an aryl group, as defined above, linked with a divalent sulfur atom and having a free valency of the sulfur atom, as phenylthio, naphthylthio and the like, the "acyl" group used alone or in combination with other radicals, is selected from a radical containing from one to eight carbon atoms, more preferably selected from formyl, acetyl, propanoyl, butanoyl , isobutanoyl, pentanoyl, hexanoyl, heptanoyl, benzoyl and the like, which may be substituted, in the present, the "acyloxy" group used alone or in combination with other radicals, is selected from a suitable acyl group, as defined above, directly linked to an oxygen atom, more preferably these groups are selected from acetyloxy, propionyloxy, butanoyloxy, iso-butanoyloxy, benzoyloxy and the like, the group "oxo" or "car" bonyl "used alone (-C = 0-) or in combination with other radicals such as the alkyl described above, for example," alkylcarbonyl ", denotes a carbonyl radical (-C = 0-) substituted with an alkyl radical described in previous as acyl or 52. 517 alkanoyl; the "carboxylic acid" group used alone or in combination with other radicals, denotes a -COOH group, and includes carboxylic acid derivatives such as esters and amides; the "ester" group used alone or in combination with other radicals, denotes a -C00- group, and includes carboxylic acid derivatives, more preferably, the ester entities are selected from alkoxycarbonyl, such as methoxycarbonyl, ethoxycarbonyl, and the like, which optionally it can be substituted; aryloxycarbonyl group such as phenoxycarbonyl, naphthyloxycarbonyl, and the like, which optionally may be substituted; aralkoxycarbonyl group such as benzyloxycarbonyl, phenethyloxycarbonyl, naphthylmethoxycarbonyl, and the like, which optionally may be substituted; heteroaryloxycarbonyl, heteroaralkoxycarbonyl, wherein the heteroaryl group is as defined above, which optionally may be substituted; heterocyclyloxycarbonyl, wherein the heterocyclic group is as defined above, which optionally may be substituted; the "aminocarbonyl" group used alone or in combination with other radicals can be selected from "aminocarbonyl", "aminocarbonylalkyl", "N-" 52. 517 alkylaminocarbonyl "," N-arylaminocarbonyl "," N, N-dialkylaminocarbonyl "," N-alkyl-N-arylaminocarbonyl "," N-alkyl-N-hydroxyaminocarbonyl ", and" N-alkyl-N-hydroxyaminocarbonylalkyl ", each one of which may optionally be substituted The terms "N-alkylaminocarbonyl" and "N, N-dialkylaminocarbonyl" denote aminocarbonyl radicals, as defined above, substituted with an alkyl radical and with two alkyl radicals, respectively. are "short chain alkylaminocarbonyls" having small alkyl radicals, as described above, attached to an aminocarbonyl radical The terms "N-arylaminocarbonyl" and "N-alkyl-N-arylaminocarbonyl" denote substituted aminocarbonyl radicals, respectively , with an aryl radical or an alkyl, and an aryl radical The term "aminocarbonylalkyl" includes alkyl radicals substituted with aminocarbonyl radicals, the "hydroxyalkyl" group used alone or in combination with In other radicals, it is selected from an alkyl group, as defined above, substituted with one or more hydroxyl radicals, more preferably, the groups are selected from hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxybutyl, hydroxypentyl, hydroxyhexyl and the like; - the "aminoalkyl" group used alone or in 52. 517 combination with other radicals, denotes an amino entity (-NH2) attached to an alkyl radical, as defined above, which may be substituted, for example, substituted mono- and diaminoalkyl. Here, the term "alkylamino" used alone or in combination with other radicals, denotes an alkyl radical, as defined above, attached to an amino group, which may be substituted, for example, mono- and dialkylamino substituted; the "alkoxyalkyl" group used alone or in combination with other radicals, denotes an alkoxy group, as defined above, attached to an alkyl group, as defined above, more preferably, the group may be selected from methoxymethyl, ethoxymethyl , methoxyethyl, ethoxyethyl and the like; the "alkylthio" group used alone or in combination with other radicals, denotes a straight or branched or cyclic monovalent substituent containing an alkyl group, as defined above, linked through a divalent sulfur atom, having a free valence for the sulfur atom, more preferably, the groups can be selected from methylthio, ethylthio, propylthio, butylthio, pentthylthio and the like or cyclic alkylthio selected from cyclopropylthio, cyclobutylthio, cyclopentylthio, cyclohexylthio and the like, which 52. 517 optionally may be substituted; the "thioalkyl" group used alone or in combination with other radicals, denotes an alkyl group, as defined above, attached to a group of formula -SR ', wherein R' represents hydrogen, alkyl or aryl group, for example, thiomethyl, methylthiomethyl, phenylthiomethyl and the like, which optionally may be substituted. the "alkoxyamino" group used alone or in combination with other radicals, represents a suitable alkoxy group, as defined above, attached to an amino group; the "hydroxyamino" group used alone or in combination with other radicals, represents an -NHOH entity and may optionally be substituted with suitable groups selected from those described above; the group "sulfenyl" or "sulfenyl derivatives" used alone or in combination with other radicals, represents a bivalent group, -SO- or RxSO, wherein Rx is an alkyl, aryl, heteroaryl, heterocyclyl group, optionally substituted, selected from the group consisting of that were described in the above; the group "sulfonyl" or "sulfone derivatives" used alone or in combination with other radicals, with others 52. 517 terms such as alkylsulfonyl, represents a divalent radical -S02- or RxS02-, wherein Rx is as defined above. More preferably, the groups can be selected from "alkylsulfonyl" wherein the suitable alkyl radical, selected from those described above, is bonded to a sulfonyl radical, eg, methylsulfonyl, ethylsulfonyl, propylsulfonyl and the like , "arylsulfonyl" wherein an aryl radical, as defined above, is attached to a sulfonyl radical, eg, phenylsulfonyl and the like; the "alkylsulfonyloxy" group used alone or in combination, refers to an alkylsulfonyl group as defined above, directly attached to an oxygen atom. Suitable groups and substituents in the groups can be selected from those described elsewhere in the specification. Particularly useful compounds can be selected from: methyl 2-Methyl-5- [4- (1-phenyl-ethylidenaminooxy) -butyl] - [1,3] dioxan-2-carboxylate; 2-Methyl-5- [4- (1-phenyl-pentylideneaminooxy) -butyl] - [1,3] dioxan-2-carboxylic acid methyl ester; 5- (4-Benzylidene-aminooxy-butyl) -2-methyl- 52. 517 [1,3] dioxan-2-carboxylic acid methyl; 2-Methyl-5-. { 4- [1- (4-trifluoromethyl-phenyl) -ethylidenaminooxy] -butyl} - [1,3] Methyl dioxan-2-carboxylate; 5-. { 4- [1- (4-Fluoro-phenyl) -ethylidenaminooxy] -butyl} Methyl -2- [1,3] dioxan-2-carboxylate; 5-. { 4- [1- (4-Chloro-phenyl) -ethylidenaminooxy] -butyl} Methyl -2- [1,3] dioxan-2-carboxylate; 5-. { 4- [1- (4-Methanesulfonyl-phenyl) -ethylidenaminooxy] -butyl} Methyl -2- methyl- [1,3] dioxan-2-carboxylate; (2-Methyl-5- [4- (1-m-tolyl-ethylideneaminooxy) -butyl] - [1,3] dioxan-) -2-carboxylate. 5-. { 4- [1- (4-Butyl-phenyl) -ethylidenaminooxy] -butyl} Methyl -2- [1,3] dioxan-2-carboxylate; 2-Methyl-5- [4- (1-p-tolyl-ethylidenaminooxy) -butyl] - [1,3] dioxan-2-carboxylic acid methyl ester; 2-Methyl-5-. { 4- [1- (4-methylsulfanyl-phenyl) -ethylidenaminooxy] -butyl} - [1,3] dioxan-2-carboxylic acid methyl; 5-. { 4- [1- (4-Ethyl-phenyl) -ethylidenaminooxy] -butyl} Methyl -2- [1,3] dioxan-2-carboxylate; 5-. { 4- [1- (4-Ethoxy-phenyl) -ethylidenaminooxy] -butyl} Methyl -2- [1,3] dioxan-2-carboxylate; 5-. { 4- [1- (4-Isopropoxy-phenyl) -ethylidene-aminooxy] - 52. 517 butyl} Methyl -2- [1,3] dioxan-2-carboxylate; 2-Methyl-5-. { 4- [1- (4-phenoxy-phenyl) -ethylidenaminooxy] -butyl} - [1,3] dioxan-2-carboxylic acid methyl; 5-. { 4- [1- (4-Isobutyl-phenyl) -ethylidenaminooxy] -butyl} Methyl -2- [1,3] dioxan-2-carboxylate; 5-. { 4- [1- (4-Methoxy-phenyl) -ethylidenaminooxy] -butyl} Methyl -2- [1,3] dioxan-2-carboxylate; 5- [4- (1-Biphenyl-4-yl-ethylidenaminooxy) -butyl] -2-methyl- [1,3] dioxan-2-carboxylic acid methyl ester; 5-. { 4- [1- (3-Chloro-4-fluoro-phenyl) -ethylidene-aminooxy] -butyl} Methyl -2- methyl- [1,3] dioxan-2-carboxylate; 5-. { 4- [1- (3, 4-Dimethyl-phenyl) -ethylidenaminooxy] -butyl} Methyl -2- [1,3] dioxan-2-carboxylate; 5- . { 5- [1- (3, 4-Dimethyl-phenyl) -ethylidenaminooxy] -pentyl} Methyl -2- [1,3] dioxan-2-carboxylate; 5-. { 4- [1- (4-Methoxy-3-methyl-phenyl) -ethylidenaminooxy] -butyl} Methyl -2- methyl- [1,3] dioxan-2-carboxylate; 5-. { 4- [1- (3, 4-Dimethoxy-phenyl) -ethylidenaminooxy] -butyl} Methyl -2- [1,3] dioxan-2-carboxylate; 5-. { 4- [1- (3-Fluoro-4-methoxy-phenyl) -ethylidenaminooxy] -butyl} Methyl -2- methyl- [1,3] dioxan-2-carboxylate; 52. 517 (5-. {4- [1- (4-Methoxy-phenyl) -propylideneaminooxy] -butyl} -2-methyl- [1,3] dioxan-) -2-carboxylate; . { 2-Methyl-5- [4- (1-p-tolyl-propylidenaminooxy) -butyl] - [1,3] dioxan} -2-carboxylate; . { 2-Methyl-5- [4- (l-pyridin-2-yl-ethylidenaminooxy) -butyl] - [1,3] dioxan-} -2-carboxylate; . { 2-Methyl-5- [4- (l-pyridin-3-yl-ethylidenaminooxy) -butyl] - [1,3] dioxan-} -2-carboxylate; . { 2-Methyl-5- [4- (l-pyridin-4-yl-ethylidenaminooxy) -butyl] - [1,3] dioxan-} -2-carboxylate; 5- [4- (1-Benzo [1,3] dioxol-5-yl-ethylidenaminooxy) -butyl] -2-methyl- [1,3] dioxan-2-carboxylic acid methyl; Methyl-2-methyl-5- [4- (1-thiophen-2-yl-ethylidenaminooxy) -butyl] - [1,3] dioxan-2-carboxylic acid methyl ester; 5- [4- (1-Benzofuran-2-yl-ethylidenaminooxy) -butyl] -2-methyl- [1,3] dioxan-2-carboxylic acid methyl ester; 5- [5- (1-Benzofuran-2-yl-ethylidenaminooxy) -pentyl] -2-methyl- [1,3] dioxan-2-carboxylic acid methyl ester; 5-. { 4- [1- (2, 3-Dimethyl-benzofuran-6-yl) -ethylidenaminooxy] -butyl} Methyl -2- methyl- [1,3] dioxan-2-carboxylate; 2-Methyl-5-. { 4- [1- (1-methyl-1H-indol-3-yl) -ethylidene-aminooxy] -butyl} - [1,3] Methyl dioxan-2-carboxylate; 52. 517 methyl 2-methyl-5- [5- (1-naphthalen-2-yl-ethylidenaminooxy) -pentyl] - [1,3] dioxan-2-carboxylate; 2-Methyl-5- [4- (1-naphthalen-2-yl-ethylidenaminooxy) -butyl] - [1,3] dioxan-2-carboxylic acid methyl ester; 2-Methyl-5-. { 4- [1- (5, 6, 7, 8-tetrahydro-naphthalen-2-yl) -ethylidenaminooxy] -butyl} - [1,3] dioxan-2-carboxylic acid methyl; 5- . { 4- [1- (4-Methoxymethoxy-phenyl) -ethylidenaminooxy] -butyl} Methyl -2- [1,3] dioxan-2-carboxylate; 5-. { 4- [1- (4-Hydroxy-phenyl) -ethylidenaminooxy] -butyl} Methyl -2- [1,3] dioxan-2-carboxylate; 5-. { 4- [1- (4-Methanesulfonyloxy-phenyl) -ethylidenaminooxy] -butyl} Methyl -2- methyl- [1,3] dioxan-2-carboxylate; 2-Methyl-5- [4- (1-naphthalen-2-yl-ethylidenaminooxy) -butyl] - [1,3] dioxan-2-carboxylic acid octyl ester; 2-Methyl-5- [4- (1-phenyl-ethylidenaminooxy) -butyl] - [1, 3] dioxan-2-carboxylic acid and its pharmaceutically acceptable salts; 5- (4-Benzylideneaminooxy-butyl) -2-methyl- [1, 3] dioxan-2-carboxylic acid and its pharmaceutically acceptable salts; 2-Methyl-5-acid. { 4- [1- (4-trifluoromethyl-phenyl) -ethylidenaminooxy] -butyl} - [1, 3] dioxan-2-carboxylic acid and its pharmaceutically acceptable salts; 52. 517 Acid 5-. { 4- [1- (4-fluoro-phenyl) -ethylidenaminooxy] -butyl} -2-methyl- [1,3] dioxan-2-carboxylic acid and its pharmaceutically acceptable salts; Acid 5-. { 4- [1- (4-chloro-phenyl) -ethylidenaminooxy] -butyl} -2-methyl- [1,3] dioxan-2-carboxylic acid and its pharmaceutically acceptable salts; Acid 5-. { 4- [1- (4-methanesulfonyl-phenyl) -ethylidenaminooxy] -butyl} -2-methyl- [1,3] dioxan-2-carboxylic acid and its pharmaceutically acceptable salts; 2-Methyl-5- [4- (1-p-tolyl-ethylideneaminooxy) -butyl] - [1, 3] dioxan-2-carboxylic acid and its pharmaceutically acceptable salts; Acid 5-. { 4- [1- (3-Chloro-4-fluoro-phenyl) -ethylidenaminooxy] -butyl} -2-methyl- [1,3] dioxan-2-carboxylic acid and its pharmaceutically acceptable salts; Acid 5-. { 4- [1- (4-Butyl-phenyl) -ethylidenaminooxy] -butyl} -2-methyl- [1,3] dioxan-2-carboxylic acid and its pharmaceutically acceptable salts; 2-methyl-5-acid. { 4- [1- (4-Methylsulphane-phenyl) -ethylidene-aminooxy] -butyl} - [1, 3] dioxan-2-carboxylic acid and its pharmaceutically acceptable salts; Acid 5-. { 4- [1- (4-ethyl-phenyl) -ethylidenaminooxy] -butyl} -2-methyl- [1,3] dioxan-2-carboxylic acid and its pharmaceutically acceptable salts; Acid 5-. { 4- [l- (3,4-dimethyl-phenyl) - 52. 517 ethylidenaminooxy] -butyl} -2-methyl- [1,3] dioxan-2-carboxylic acid and its pharmaceutically acceptable salts; Acid 5-. { 5- [1- (3, 4-dimethyl-phenyl) -ethylidenaminooxy] -pentyl} -2-methyl- [1,3] dioxan-2-carboxylic acid and its pharmaceutically acceptable salts; 5-. { 4- [1- (4-Ethoxy-phenyl) -ethylidenaminooxy] -butyl} -2-methyl- [1,3] dioxan-2-carboxylic acid and its pharmaceutically acceptable salts; Acid 5-. { 4- [1- (4-isopropoxy-phenyl) -ethylidenaminooxy] -butyl} -2-methyl- [1,3] dioxan-2-carboxylic acid and its pharmaceutically acceptable salts; Acid 5-. { 4- [1- (4-methoxy-3-methyl-phenyl) -ethylidenaminooxy] -butyl} -2-methyl- [1,3] dioxan-2-carboxylic acid and its pharmaceutically acceptable salts; 2-methyl-5-acid. { 4- [1- (4-phenoxy-phenyl) -ethylidenaminooxy] -butyl} - [1, 3] dioxan-2-carboxylic acid and its pharmaceutically acceptable salts; Acid 5-. { 4- [1- (3, 4-dimethoxy-phenyl) -ethylidenaminooxy] -butyl} -2-methyl- [1,3] dioxan-2-carboxylic acid and its pharmaceutically acceptable salts; Acid 5-. { 4- [1- (4-Isobutyl-phenyl) -ethylidenaminooxy] -butyl} -2-methyl- [1,3] dioxan-2-carboxylic acid: 5- Acid. { 4- [1- (3-fluoro-4-methoxy-phenyl) -ethylidenaminooxy] -butyl} -2-methyl- [1,3] dioxan-2-carboxylic acid and its pharmaceutically acceptable salts; 52. 517 2-Methyl-5- [5- (1-naphthalen-2-yl-ethylidenaminooxy) -pentyl] - [1, 3] dioxan-2-carboxylic acid and its pharmaceutically acceptable salts; 2-Methyl-5- [4- (1-naphthalen-2-yl-ethylidenaminooxy) -butyl] - [1, 3] dioxan-2-carboxylic acid and its pharmaceutically acceptable salts; 2-methyl-5-acid. { 4- [1 - (5, 6, 7, 8-tetrahydro-naphthalen-2-yl) -ethylidene-aminooxy] -butyl} - [1,3] dioxan-2-carboxylic acid and its pharmaceutically acceptable salts; Acid 5-. { 4- [1- (4-hydroxy-phenyl) -ethylidenaminooxy] -butyl} -2-methyl- [1,3] dioxan-2-carboxylic acid and its pharmaceutically acceptable salts; Acid 5-. { 4- [1- (4-methoxy-phenyl) -ethylidenaminooxy] -butyl} -2-methyl- [1,3] dioxan-2-carboxylic acid and its pharmaceutically acceptable salts; Acid 5-. { 4- [1- (4-methanesulfonyloxy-phenyl) -ethylidenaminooxy] -butyl} -2-methyl- [1,3] dioxan-2-carboxylic acid and its pharmaceutically acceptable salts; 2-Methyl-5- [4- (1-thiophen-2-yl-ethylideneaminooxy) -butyl] - [1, 3] dioxan-2-carboxylic acid and its pharmaceutically acceptable salts; 5- [4- (1-Benzo [1,3] dioxol-5-yl-ethylidenaminooxy) -butyl] -2-methyl- [1,3] dioxan-2-carboxylic acid and its pharmaceutically acceptable salts; 5- [4- (1-biphenyl-4-yl-ethylidene-aminooxy) - acid 52. 517-butyl] -2-methyl- [1,3] dioxan-2-carboxylic acid and its pharmaceutically acceptable salts; 2-Methyl-5- [4- (1-phenyl-pentilideneaminooxy) -butyl] - [1, 3] dioxan-2-carboxylic acid and its pharmaceutically acceptable salts; 5- [4- (1-Benzofuran-2-yl-ethylidenaminooxy) -butyl] -2-methyl- [1, 3] dioxan-2-carboxylic acid and its pharmaceutically acceptable salts; 5- [5- (1-Benzofuran-2-yl-ethylidenaminooxy) -pentyl] -2-methyl- [1, 3] dioxan-2-carboxylic acid and its pharmaceutically acceptable salts; Acid 5-. { 4- [1- (2, 3-dimethyl-benzofuran-6-yl) -ethylidenaminooxy] -butyl} -2-methyl- [1,3] dioxan-2-carboxylic acid and its pharmaceutically acceptable salts; 2-methyl-5-acid. { 4- [1- (1-methyl-1H-indol-3-yl) -ethylidene-aminooxy] -butyl} - [1, 3] dioxan-2-carboxylic acid and its pharmaceutically acceptable salts; 2-Methyl-5- [4- (1-m-tolyl-ethylideneaminooxy) -butyl] - [1, 3] dioxan-2-carboxylic acid and its pharmaceutically acceptable salts; Acid 5-. { 4- [1- (4-methoxy-phenyl) -propylideneaminooxy] -butyl} -2-methyl- [1,3] dioxan-2-carboxylic acid and its pharmaceutically acceptable salts; 2-Methyl-5- [4- (1-p-tolyl-propylideneaminooxy) -butyl] - [1, 3] dioxan-2-carboxylic acid and its 52. 517 pharmaceutically acceptable salts; 2-Methyl-5- [4- (1-pyridin-2-yl-ethylidenaminooxy) -butyl] - [1, 3] dioxan-2-carboxylic acid and its pharmaceutically acceptable salts; 2-Methyl-5- [4- (1-pyridin-3-yl-ethylideneaminooxy) -butyl] - [1, 3] dioxan-2-carboxylic acid and its pharmaceutically acceptable salts; 2-Methyl-5- [4- (1-pyridin-4-yl-ethylidenaminooxy) -butyl] - [1, 3] dioxan-2-carboxylic acid and its pharmaceutically acceptable salts; 2-methyl-5-acid. { 4- [1- (5-methyl-furan-2-yl) -ethylidenaminooxy] -butyl} - [1, 3] dioxan-2-carboxylic acid and its pharmaceutically acceptable salts. The new compounds of this invention can be prepared using the reactions and techniques shown in the following scheme and described in this section. The reactions are carried out in appropriate solvents for the reagents and materials used and are suitable for the transformations that take place. One skilled in the art will realize that the nature and order of the synthetic steps presented may vary in order to optimize the formation of the compounds of the present invention.

Scheme: 52. 517 i. reaction of the compounds of general formula (II), wherein all symbols are as defined above, with compounds of general formula (III), wherein all symbols are as defined above, and L represents a leaving group as halogen, mesylate, tosylate, triflate and the like and R2 represents an alkyl group, and the compound of general formula (I) is obtained, wherein all the symbols are as defined above, and R2 represents an alkyl group. ii. hydrolysis of the compound of general formula (I), wherein R2 is alkyl and all other symbols are as defined above, to give another compound of general formula (I) wherein R2 is H all other symbols are as defined previously. iii. the compounds of formula (I) optionally can be converted to their pharmaceutically salts 52. 517 acceptable by techniques known in the art. Step I: The compound of formula (I) can be prepared by reacting the compound of formula (II) with the compound of formula (III) under the appropriate conditions. The reaction can be carried out in the presence of solvents such as acetone, tetrahydrofuran, dimethyl sulfoxide, dioxane, acetonitrile, dimethyl formamide, dimethoxy ethane, benzene, toluene, petroleum ester, heptane, hexane, 2-butanone, xylene, alcohols as methanol, ethanol, propanol, butanol, iso-butanol, tert-butanol, pentanol and the like or mixtures thereof. Bases such as alkali metal carbonates, for example, K2C03, Na2C03, CsC03 and the like can be used in this reaction; or alkali metal hydroxides such as NaOH, KOH and the like. Alkali metal hydrides such as NaH, KH may be used when the solvent used is not protic or contains a carbonyl group. The reaction can be carried out at a temperature in the range of 0 ° C to the reflux temperature of the solvent (s) used and the reaction time can vary from 1 to 48 hours. Step II: The compound of formula (I) can be hydrolyzed to obtain another compound of formula (I) by means of a suitable base, for example, NaOH, LiOH, KOH and the like. The reaction can be carried out in solvents 52. 517 suitable, for example, alcohols such as methanol, ethanol and the like, THF, water or mixtures thereof. The reaction can be carried out at a temperature in the range of 20 ° C at the reflux temperature of the solvent (s) used and the reaction time can vary from 1 to 48 hours. The invention is explained in more detail by the examples described below, which are presented for illustrative purposes only and which will therefore not be considered as limiting the scope of the invention. The spectroscopic data of 1H NMR presented in the following examples were obtained by means of a 300 MHz spectrometer (Bruker AVANCE-300) and reported on an S-scale. Unless otherwise mentioned, the solvent used for NMR is CDCI3 and tetramethylsilane was used as the internal standard.

Example 1 Methyl 2-methyl-5- [4- (1-phenyl-ethylidenaminooxy) -butyl] - [1, 3] dioxan-2-carboxylate A mixture of 1-phenyl-ethanone oxime (1.13 g), 5- (4-chloro-butyl) -2-methyl- [1,3] dioxan-2-carboxylic acid methyl (prepared by known processes) (2.5 g) and cesium carbonate (4.0 g) in anhydrous dimethyl formamide was kept under stirring at 60 ° C for 18 hours in an inert atmosphere. The 52. 517 reaction mixture was cooled to room temperature, poured into ice water and extracted with ethyl acetate. The combined organic extract was washed with water, brine solution, dried over sodium sulfate and evaporated under reduced pressure. The crude product was run by flash chromatography on silica gel using 7% ethyl acetate in petroleum ether as eluent and 2.5 g of the pure product was obtained. XH NMR: 1.1 (2H, m), 1.4 (2H, m), 1.5 (3H, s), 1.7 (2H, m), 2.0 (1H, m), 2.2 (3H, s), 3.4 (2H, t , J = 12.5 Hz), 3.8 (3H, s), 3.9 (2H, dd, J = 12.0 and 4.6 Hz), 4.1 (2H, t, J = 6.4 Hz), 7.3 (3H, m), 7.6 (2H , m). Yield: 85% The following compounds were prepared by procedures similar to that described in Example 1 with appropriate variations of reagents, reaction conditions and amounts of reagents.

Example 2 Methyl 2-methyl-5- [4- (1-phenyl-pentylideneaminooxy) -butyl] - [1,3] dioxan-2-carboxylate XH NMR: 0.9 (3H, t, J = 7.2 Hz), 1.0 (2H, m), 1.4 (4H, m), 1.5 (5H, m), 1.7 (2H, m), 2.0 (1H, m), 2.7 (2H, t, J = 7.4 Hz), 3.4 (2H, t, J = 11.5 Hz), 3.8 (3H, s), 4.0 (2H, dd, J = 12.1 and 4.9 Hz), 4.2 (2H, t, J = 6.4 Hz) , 7.3 (3H, m), 7.6 (2H, m). Performance: 54% 52. 517 Example 3 Methyl 5- (4-benzylideneaminooxybutyl) -2-methyl- [1,3] dioxan-2-carboxylate 1H NMR: 1.1 (2H, m), 1.4 (2H, m), 1.5 (3H, s), 1. 73 (2H, m), 2.0 (1H, m), 3.4 (2H, t, J = 11.7 Hz), 3.8 (3H, s), 3.9 (2H, dd, J = 12.1 and 4.6 Hz), 4.1 (2H , t, J = 6.4 Hz), 7.3 (3H, m), 7.5 (2H, m), 8.0 (1H, s). Performance: 82% Example 4 2-methyl-5-. { 4- [1- (4-trifluoromethyl-phenyl) -ethylidenaminooxy] -butyl} - [1, 3] Methyl dioxan-2-carboxylate XH NMR: 1.0 (2H, m), 1.3 (2H, m), 1.5 (3H, s), 1.7 (2H, m), 2.0 (1H, m) , 2.2 (3H, s), 3.4 (2H, t, J = 11.8 Hz), 3.8 (3H, s), 4.0 (2H, dd, J = 12.1 and 4.6 Hz), 4.2 (2H, t, J = 6.5 Hz), 7.6 (2H, d, J = 8.3 Hz), 7.7 ( 2H, d, J = 8.2 Hz).

Performance: 47% Example 5 5-. { 4- [1- (4-fluoro-phenyl) -ethylidenaminooxy] -butyl} Methyl -2- [1, 3] dioxan-2-carboxylate XH NMR: 1.1 (2H, m), 1.4 (2H, m), 1.5 (3H, s), 1. 7 (2H, m), 2.0 (1H, m), 2.2 (3H, s), 3.4 (2H, t, J = 11.5 Hz), 3.8 (3H, s), 3.9 (2H, dd, J = 12.0 and 4.6 Hz), 4.1 (2H, 52. 517 t, J = 6.4 Hz), 7.0 (2H, m), 7.6 (2H, m). Performance: 79% Example 6 5-. { 4- [1- (4-chloro-phenyl) -ethylidenaminooxy] -butyl} Methyl -2- [1,3] dioxan-2-carboxylic acid 1ti NMR: 1.1 (2H, m), 1.4 (2H, m), 1.5 (3H, s), 1. 7 (2H, m), 2.0 (1H, m), 2.2 (3H, s), 3.4 (2H, t, J = 11.7 Hz), 3.8 (3H, s), 3.9 (2H, dd, J = 12.0 and 4.6 Hz), 4.1 (2H, t, J = 6.4 Hz), 7.3 (2H, dd, J = 6.7 and 2.0 Hz), 7.6 (2H, dd, J = 6.7 and 1.9 Hz). Performance: 86% Example 7 5-. { 4- [1- (4-methanesulfonyl-phenyl) -ethylidenaminooxy] -butyl} Methyl -2- [1, 3] dioxan-2-carboxylic acid XH NMR: 1.12 (2H, m), 1.4 (2H, m), 1.5 (3H, s), 1. 7 (2H, m), 2.0 (1H, m), 2.2 (3H, s), 3.0 (3H, s), 3.4 (2H, t, J = 11.7 Hz), 3.8 (3H, s), 4.0 (2H, dd, J = 12.0 and 4.6 Hz), 4.2 (2H, t, J = 6.4 Hz), 7.8 (2H, dd, J = 6.9 and 1.8 Hz), 7.9 (2H, d, J = 8.5 Hz). Performance: 66% Example 8 (Methyl 2-methyl-5- [4- (1-m-tolyl-ethylidenaminooxy) -butyl] - [1,3] dioxan-) -2-carboxylate xti NMR: 1. 0 (2H, m), 1. 37 (2H, m), 1. 51 (3H, s), 52 517 1.67 (2H, m), 2.06 (1H, m), 2.2 (3H, s), 2.37 (3H, s), 3.4 (2H, t, J = 11.5 Hz), 3.83 (3H, s), 3.98 ( 2H, dd, J = 4.38 and 11.7 Hz), 4.1 (2H, t, J = 6.43Hz), 7.1 (2H, m), 7.4 (2H, m). Performance: 49% Example 9 5-. { 4- [1- (4-Butyl-phenyl) -ethylidenaminooxy] -butyl} Methyl -2- methyl- [1,3] dioxan-2-carboxylate 1H NMR: 0.91 (3H, t, J = 7.26 Hz), 1.07 (2H, m), 1.36 (4H, m), 1.51 (3H, s), 1.60 (2H, m), 1.68 (2H, m), 2. 04 (1H, m), 2.19 (3H, s), 2.61 (2H,, t, J = 7.53 Hz), 3.40 (2H, t, J = 11.58 Hz), 3.82 (3H, s), 3.97 (2H, dd, J = 11.88 and 4. 5 Hz), 4.14 (2H, t, J = 6.39 Hz), 7.16 (2H, d, J = 8.1 Hz), 7.53 (2H, d, J = 8.07 Hz). Performance: 46% Example 10 Methyl 2-methyl-5- [4- (1-p-tolyl-ethylidenaminooxy) -butyl] - [1,3] dioxan-2-carboxylate XH NMR: 1.04-1.11 (2H, m), 1.37- 1.40 (2H, m), 1.51 (3H, s), 1.64-1.71 (2H, m) 2.09 (1H, m), 2.19 (3H, s), 2. 35 (3H, s), 3.40 (2H, t, J = 11.61 Hz), 3.82 (3H, s),, 3.96 (2H, dd, J = 12.06 and 4.65 Hz), 4.14 (2H, t, J = 7.42 Hz), 7.16 (2H, d, J = 6.27 Hz), 7.52 (2H, d, J = 8.13 Hz). Performance: 52% 52. 517 Example 11 2-methyl-5-. { 4- [1- (4-methylsulfanyl-phenyl) -ethylidenaminooxy] -butyl} - [1,3] dioxan-2-carboxylic acid methyl 1Ü NMR: 1.04-1.11 (2H, m), 1.34-1.42 (2H, m), 1. 51 (3H, s), 1.66-1.71 (2H, m) 2.08 (1H, m), 2.38 (3H, s), 2.49 (3H, s), 3.40 (2H, t, J = 11.67 Hz), 3.82 ( 3H, s), 3.96 (2H, dd, J = 12.03 and 4.56 Hz), 4.14 (2H, t, J = 6.42 Hz), 7.22 (2H, d, J = 8.4 Hz), 7.55 (2H, d, J = 8.4 Hz). Performance: 58% Example 12 5-. { 4- [1- (4-ethyl-phenyl) -ethylidenaminooxy] -butyl} Methyl -2- [1, 3] dioxan-2-carboxylate XH NMR: 1.06-1.11 (2H, m), 1.23 (3H, t, J = 7.59 Hz), 1.34-1.40 (2H, m), 1.51 (3H, s), 1.69 (2H, m), 2.00 (1H, m), 2.20 (3H, s), 2.64 (2H, q, J = 15.18 and 7.62 Hz), 3.40 (2H, t, J = 11.76 Hz), 3.83 (3H, s), 3.97 (2H, dd, J = 12.09 and 4.68 Hz), 4.14 (2H, t, J = 6.45 Hz), 7.18 (2H, d, J = 8.25 Hz), 7.55 (2H, d, J = 1.74 Hz). Performance: 54% Example 13 5-. { 4- [1- (4-Ethoxy-phenyl) -ethylidenaminooxy] -butyl} Methyl -2- [1,3] dioxan-2-carboxylate XH NMR: 1.09 (2H, m), 1.3 (2H, m), 1.4 (3H, t, 52. 517 J = 6.9 Hz), 1.51 (3H, m), 1.68 (2H, m), 2.04 (1H, m), 2.18 (3H, s), 3.40 (2H, t, J = 11.67 Hz), 3.82 (3H , s), 3.96 (2H, dd, J = 12.03 and 4.53 Hz), 4.04 (2H, q, J = 13.98 and 6.99 Hz), 4.13 (2H, t, J = 6.42 Hz), 6.86 (2H, d, J = 8.76 Hz), 7.56 (2H, d, J = 8.76 Hz). Performance: 38% Example 14 5-. { 4- [1- (4-isopropoxy-phenyl) -ethylidenaminooxy] -butyl} Methyl -2- methyl- [1,3] dioxan-2-carboxylate XH NMR: 1.05 (2H, m), 1.32 (3H, s), 1.34 (3H, s), 1.4 (2H, m), 1.51 ( 3H, s), 1.66 (2H, m), 2.04 (1H, m), 2.18 (3H, s), 3.40 (2H, t, J = 11.64 Hz), 3.82 (3H, s), 3.96 (2H, dd , J = 11.94 and 4.56 Hz), 4.13 (2H, t, J = 6.42 Hz), 4.56 (1H, m), 6.86 (2H, d, J = 8.76 Hz), 7.56 (2H, d, J = 8.76 Hz ). Performance: 47% Example 15 2-methyl-5-. { 4- [1- (4-phenoxy-phenyl) -ethylidene-aminooxy] -butyl} - [1,3] dioxan-2-methyl carboxylate XH NMR: 1.04-1.11 (2H, m), 1.34-1.40 (2H, m), 1. 51 (3H, s), 1.64-1.73 (2H, m), 2.05 (1H, m), 2.20 (3H, s), 3.40 (2H, t, J = 11.61 Hz), 3.83 (3H, s), 3.96 (2H, dd, J = 12.09 and 4.65 Hz), 4.15 (2H, t, J = 6.42 Hz), 6.97-7.03 (4H, m), 7.12 (1H, m), 7.32-7.37 (2H, m), 7.60 (2H, dd , 52. 517 J = 6.81 and 2.01 Hz). Performance: 58% Example 16 5-. { 4- [1- (4-Isobutyl-phenyl) -ethylidenaminooxy] -butyl} Methyl -2- methyl- [1,3] dioxan-2-carboxylate XH NMR: 0.88 (3H, s), 0.90 (3H, s), 1.06-1.11 (2H, m), 1.37 (2H, m), 1.51 (3H, s), 1.66-1.71 (2H, m), 1.84 (1H, m), 2.04 (1H, m), 2.20 (3H, s), 2.47 (2H, d, J = 7.17 Hz), 3.40 (2H, t, J = 11.67 Hz), 3.83 (3H, s), 3.97 (2H, dd, J = 12.06 and 4.68 Hz), 4.15 (2H, t, J = 6.24 Hz), 7.12-7.15 (2H, d, J = 8.22 Hz), 7.52-7.55 (2H, d, J = 8.22 Hz). Performance: 50% Example 17 5-. { 4- [1- (4-methoxy-phenyl) -ethylidenaminooxy] -butyl} Methyl -2- [1, 3] dioxan-2-carboxylate XH NMR: 1.04-1.11 (2H, m), 1.34-1.40 (2H, m), 1. 51 (3H, s), 1.64-1.71 (2H, m) 2.04 (1H, m), 2.19 (3H, s), 3. 40 (2H, t, J = 11.61 Hz), 3.82 (3H, s), 3.83 (3H, s) 3.96 (2H, dd, J = 12.06 and 4.68 Hz), 4.13 (2H, t, J = 6.42 Hz) , 7.87-6.91 (2H, m), 7.56-7.60 (2H, m). Performance: 43% Example 18 5- [4- (1-biphenyl-4-yl-ethylidenaminooxy) -butyl] -2-methyl- [1,3] dioxan-2-carboxylic acid methyl ester 52. 517 XH NMR: 1.1 (2H, m), 1.4 (2H, m), 1.5 (3H, s), 1. 7 (2H, m), 2.0 (1H, m), 2.2 (3H, s), 3.4 (2H, t, J = 11.7 Hz), 3.8 (3H, s), 4.0 (2H, dd, J = 12.1 and 4.7 Hz), 4.2 (2H, t, J = 6.4 Hz), 7.3 (1H, m), 7.4 (2H, m), 7.6 (4H, m), 7.7 (2H, m). Performance: 67% Example 19 5-. { 4- [1- (3-Chloro-4-fluoro-phenyl) -ethylidenaminooxy] -butyl} Methyl -2- methyl [1, 3] dioxan-2-carboxylate XH NMR: 1.04-1.12 (2H, m), 1.34-1.39 (2H, m), 1.51 (3H, s), 1.64-1.71 (2H , m), 2.04 (1H, m), 2.18 (3H, s), 3.40 (2H, t, J = 11.7 Hz), 3.83 (3H, s), 3.96 (2H, dd, J = 12.03y 4.62 Hz) , 4.15 (2H, t, J = 6.45 Hz), 7.1 (1H, t, J = 8.7 Hz), 7.47-7.53 (1H, m), 7.69-7.72 (1H, dd, J = 7.17 and 2.4 Hz). Performance: 39% Example 20 5-. { 4- [1- (3, 4-dimethyl-phenyl) -ethylidenaminooxy] -butyl} Methyl -2- [1, 3] dioxan-2-carboxylic acid XH NMR: 1.04-1.11 (2H, m), 1.34-1.40 (2H, m), 1. 51 (3H, s), 1.56-1.71 (2H, m), 2.05 (1H, m), 2.19 (3H, s), 2.26 (3H, s), 2.27 (3H, s), 3.40 (2H, t, J = 11.73 Hz), 3. 83 (3H, s), 3.96 (2H, dd, J = 12.27 and 4.68 Hz), 4.14 (2H, t, J = 6.45 Hz), 7.12 (1H, d, J = 7.89 Hz), 7.33 (1H, dd , J = 52. 517 7.83 and 1.71 Hz), 7.41 (1H, s). Performance: 45% Example 21 5-. { 5- [1- (3,4-dimethyl-phenyl) -ethylidenaminooxy] -pentyl} Methyl -2- methyl [1, 3] dioxan-2-carboxylate XH NMR: 1.02-1.07 (2H, m), 1.25-1.37 (4H, m), 1.51 (3H, s), 1.64-1.71 (2H , m), 2.02 (1H, m), 2.19 (3H, s), 2.26 (3H, s), 2.27 (3H, s), 3.40 (2H, t, J = 11.64 Hz), 3.83 (3H, s) , 3.96 (2H, dd, J = 12.03 and 4.62 Hz), 4.14 (2H, t, J = 6.57 Hz), 7.12 (1H, d, J = 7.86 Hz), 7.34 (1H, d, J = 7.83 Hz) , 7.41 (1H, s). Performance: 48% Example 22 5-. { 4- [1- (4-methoxy-3-methyl-phenyl) -ethylidenaminooxy] -butyl} Methyl -2- methyl [1, 3] dioxan-2-carboxylate? R NMR: 1.06-1.11 (2H, m), 1.34-1.40 (2H, m), 1.51 (3H, s), 1.57-1.71 ( 2H, m), 2.05 (1H, m), 2.18 (3H, s), 2.22 (3H, s), 3.40 (2H, t, J = 11.73 Hz), 3.83 (3H, s), 3.84 (3H, s ), 3.99 (2H, dd, J = 13.95 and 6.51 Hz), 4.13 (2H, t, J = 6.45 Hz), 6.79 (1H, d, J = 8.46 Hz), 7.39-7.45 (2H, m,). Performance: 54% Example 23 5-. { 4- [l- (3,4-dimethoxy-phenyl) -ethylidene-aminooxy] - 52. 517 butyl} Methyl -2- methyl- [1,3] dioxan-2-carboxylate 1H NMR: 1.04-1.12 (2H, m), 1.33-1.40 (2H, m), 1.51 (3H, s), 1.64-1.71 (2H , m) 2.05 (1H, m), 2.19 (3H, s), 3.40 (2H, t, J = 11.64 Hz), 3.83 (3H, s), 3.90 (3H, s), 3.92 (3H, s), 3.97 (2H, dd, J = 12.06 and 4.68 Hz), 4.15 (2H, t, J = 6.42 Hz), 6.85 (1H, d, J = 8.52 Hz), 7.13 (1H, dd, J = 8.37 and 2.04 Hz ), 7.27 (1H, d, J = 2.01Hz). Performance: 47% Example 24 5-. { 4- [1- (3-Fluoro-4-methoxy-phenyl) -ethylidenaminooxy] -butyl} Methyl -2- methyl [1, 3] dioxan-2-carboxylate XH NMR: 1.04-1.11 (2H, m), 1.34-1.39 (2H, m), 1.51 (3H, s), 1.65-1.71 (2H , m), 2.04 (1H, m), 2.17 (3H, s), 3.40 (2H, t, J = 11.67 Hz), 3.83 (3H, s), 3.90 (3H, s), 3.96 (2H, dd, J = 12.06 and 4.65 Hz), 4.14 (2H, t, J = 6.45 Hz), 6.93 (1H, t, J = 8.64 Hz), 7.31-7.35 (1H, m), 7.42-7.47 (1H, dd, J = 12.75 and 2.13 Hz). Performance: 50% Example 25 (5-. {[4- [1- (4-methoxy-phenyl) -propylideneaminooxy] -butyl} -2-methyl- [1,3] dioxan-) -2-carboxylic acid methyl ester 1H NMR: 1.1 (5H, m), 1.4 (2H, m), 1.51 (3H, s), 1.7 (2H, m), 2.1 (1H, m), 2.7 (2H, q, J = 7.59Hz), 3.4 (2H , t, J = 11.67 Hz), 3.8 (6H, s), 3.98 (2H, dd, J = 4.56 and 52. 517 12.03 Hz), 4.1 (2H, t, J = 6.36Hz), 6.9 (2H, d, J = 8.79 Hz), 7.55 (2H, d, J = 8.79 Hz). Performance: 35% Example 26 { 2-methyl-5- [4- (1-p-tolyl-propylideneaminooxy) -butyl] - [1,3] dioxan} Methyl-2-carboxylate XH NMR: 1.1 (5H, m), 1.4 (2H, m), 1.51 (3H, s), 1. 7 (2H, m), 2.0 (1H, m), 2.35 (3H, s), 2.7 (2H, q, J = 7. 6Hz), 3.4 (2H, t, J = 11.56 Hz), 3.82 (3H, s), 3.95 (2H, dd, J = 4.5 and 12.02 Hz), 4.1 (2H, t, J = 6.3 Hz), 7.15 ( 2H, J = 8.0 Hz), 7.5 (2H, J = 8.0 Hz). Performance: 58% Example 27 { 2-methyl-5- [4- (l-pyridin-2-yl-ethylidenaminooxy) -butyl] - [1, 3] dioxan-} -2-methyl carboxylate XH NMR: 1.0 (2H, m), 1.38 (2H, m), 1.51 (3H, s), 1.7 (2H, m), 2.0 (1H, m), 2.31 (3H, s) , 3.4 (2H, t, J = 11.42), 3.83 (3H, s), 3.9 (2H, dd, J = 4.56 and 12.15 Hz), 4.2 (2H, t, J = 6.47), 7.22 (1H, m) , 7.6 (1H, m), 7.8 (1H, d, J = 8.1Hz), 8.6 (1H, d, J = 4.71 Hz). Performance: 49% Example 28 { 2-methyl-5- [4- (1-pyridin-3-yl-ethylidenaminooxy) -butyl] - [1, 3] dioxan-} -2-methyl carboxylate 52. 517 H NMR: 1.0 (2H, m), 1.4 (2H, m), 1.51 (3H, s), 1.7 (2H, m), 2.0 (1H, m), 2.23 (3H, s), 3.4 (2H, t, J = 11.4Hz), 3.83 (3H, s), 3.9 (2H, dd, J = 4.6 and 12.0 Hz), 4.2 (2H, t, J = 6.47), 7.29 (1H, m), 7.96 (1H , dd, J = 1.7 and 7.9 Hz), 8.57 (1H, d, J = 4.7Hz), 8.86 (1H, s). Performance: 39% Example 29 { 2-methyl-5- [4- (1-pyridin-4-yl-ethylidenaminooxy) -butyl] - [1, 3] dioxan-} Methyl-2-carboxylate XH NMR: 1.0 (2H, m), 1.35 (2H, m), 1.51 (3H, s), 1. 7 (2H, m), 2.0 (1H, m), 2.19 (3H, s), 3.4 (2H, t, J = 11. 73 Hz), 3.82 (3H, s), 3.9 (2H, dd, J = 4.44 and 11.79 Hz), 4. 2 (2H, t, J = 6.4 Hz), 7.5 (2H, d, J = 6.0 Hz), 8.6 (2H, d, J = 6.0Hz). Performance: 38% EXAMPLE 30 5- [4- (l-Benzo [l, 3] dioxol-5-yl-ethylidenaminooxy) -butyl] -2-methyl- [1,3] dioxan-2-carboxylic acid methyl ester XH NMR: 1.03-1.11 (2H, m), 1.31-1.39 (2H, m), 1. 51 (3H, s), 1.63-1.70 (2H, m), 2.04 (1H, m), 2.16 (3H, s), 3.40 (2H, t, J = 11.61 Hz), 3.83 (3H, s), 3.96 (2H, dd, J = 12.06 and 4.65 Hz), 4.13 (2H, t, J = 6.42 Hz), 5.97 (2H, s) 6.79 (1H, d, J = 8.1 Hz), 7.08 (1H, dd, J = 8.1 and 2.22 Hz), 7.19 (1H, d, J = 1.65 Hz). Performance: 54% 52. 517 EXAMPLE 31 Methyl 2-methyl-5- [4- (l-thiophen-2-yl-ethylidenaminooxy) -butyl] - [1,3] dioxan-2-carboxylate 1ti NMR: 1.03-1.11 (2H, m) , 1.34-1.42 (2H, m), 1. 51 (3H, s), 1.62-4.72 (2H, m) 2.04 (1H, m), 2.22 (3H, s), 3.40 (2H, t, J = 11.41 Hz), 3.83 (3H, s), 3.97 ( 2H, dd, J = 12 and 4.62 Hz), 4.21 (2H, t, J = 6.39 Hz), 7.00 (1H, dd, J = 5.07 and 3.75 Hz), 7.20 (1H, dd, J = 4.56 yl.05 Hz), 7.24 (1H, m). Performance: 46% EXAMPLE 32 5- [4- (l-Benzofuran-2-yl-ethylidenaminooxy) -butyl] -2-methyl- [1,3] dioxan-2-carboxylic acid methyl ester XH NMR: 1.1 (2H, m), 1.4 ( 2H, m), 1.5 (3H, s), 1. 7 (2H, m), 2.0 (1H, m), 2.2 (3H, s), 3.4 (2H, t, J = ll.l Hz), 3.8 (3H, s), 4.0 (2H, dd, J = 12.1 and 4.6 Hz), 4.2 (2H, t, J = 6.5 Hz), 6.9 (1H, s), 7.2-7.3 (2H, m), 7.5 (2H, m). Performance: 39% Example 33 5- [5- (1-benzofuran-2-yl-ethylidenaminooxy) -pentyl] -2-methyl- [1,3] dioxan-2-methylcarboxylate XH NMR: 1.0 (2H, m), 1.4 ( 4H, m), 1.5 (3H, s), 1.7 (2H, m), 2.0 (1H, m), 2.2 (3H, s), 3.4 (2H, t, J = 11.7 52. 517 Hz), 3.8 (3H, s), 3.9 (2H, dd, J = 12.0 and 4.6 Hz), 4.2 (2H, t, J = 6.6 Hz), 6.9 (1H, s), 7.2-7.3 (2H, m), 7.5 (2H, m). Performance: 62% Example 34 5-. { 4- [1- (2, 3-dimethyl-benzofuran-6-yl) -ethylidenaminooxy] -butyl} Methyl -2- methyl- [1,3] dioxan-2-carboxylate XH NMR: 1.06 (2H, m), 1.41 (2H, m), 1.57 (3H, s), 1.74 (2H, m), 2.05 ( 1H, m), 2.14 (3H, s), 2.26 (3H, s), 2. 38 (3H, s), 3.40 (2H, t, J = 11.53 Hz), 3.83 (3H, s), 3.97 (2H, s), 4.17 (2H, t, J = 6.13 Hz), 7.35 (lH, d, J = 8.1 Hz), 7.51 (1H, d, J = 8.01 Hz), 7.62 (1H, s). Performance: 39% Example 35 2-methyl-5-. { 4- [1- (1-methyl-1H-indol-3-yl) -ethylidene-aminooxy] -butyl} - [1,3] Methyl dioxan-2-carboxylate XH NMR: 1.05-1.13 (2H, m), 1.35-1.46 (2H, m), 1. 50 (3H, s), 1.70-1.77 (2H, m), 2.05 (1H, m), 2.23 (3H, s), 3.40 (2H, t, J = 11.46 Hz), 3.79 (3H, s), 3.82 (3H, s), 3. 97 (2H, dd, J = 11.95 and 4.032 Hz), 4.19 (2H, t, J = 6.42 Hz), 7. 17-7.31 (4H, m), 8.27 (1H, d, J = 7.71 Hz). Yield: 47% Example 36 Methyl 2-methyl-5- [5- (1-naphthalen-2-yl-ethylidenaminooxy) -pentyl] - [1,3] dioxan-2-carboxylate 1ti NMR: 1.06 (2H, m ), 1.25-1.41 (4H, m), 1.51 (3H, s), 1.73 (2H, m), 2.04 (1H, m), 2.32 (3H, s), 3.40 (2H, t, J = 11.76 Hz) , 3.82 (3H, s), 3.96 (2H, dd, J = 12.06 and 4.59 Hz), 4.21 (2H, t, J = 6.57 Hz), 7.47 (2H, m), 7.78-7.92 (4H, m), 7.98 (1H, s). Performance: 33% Example 37 Methyl 2-methyl-5- [4- (1-naphthalen-2-yl-ethylidenaminooxy) -butyl] - [1, 3] dioxan-2-carboxylate 1ti NMR: 1.06-1.14 (2H, m), 1.40 (2H, m), 1.51 (3H, s), 1.71-1.75 (2H, m) 2.06 (1H, m), 2.33 (3H, s), 3. 37-3.51 (2H, t, J = 11.6 Hz), 3.82 (3H, s), 4.00 (2H, q, J = 11.91 and 4.56 Hz), 4.21 (2H, t, J = 6.39 Hz), 7.48 (2H, m), 7. 79-7.92 (4H, m), 7.99 (1H, m). Performance: 52% Example 38 2-methyl-5-. { 4- [1- (5, 6, 7, 8-tetrahydro-naph talen-2-yl) -ethylidenaminooxy] -butyl} - [1,3] dioxan-2-methyl carboxylate XH NMR: 1. 06- 1. 11 (2H, m), 1. 38 (2H, m), 1. 51 (3H, s), 1.68 (2H, m), 1.76-1.81 (4H, m), 2.04 (1H, m), 2.18 (3H, s), 2.77 (4H, m), 3.40 (2H, t, J = 11.61 Hz), 3.83 (3H, s), 3.96 (2H, dd, J = 11.91 and 4.47 Hz), 4.14 (2H, t, J = 6.45 Hz), 7.03-7.06 (1H, d, J = 7.74 Hz), 7.32-7.35 (2H, m). Performance: 50% Example 39 5-. { 4- [1- (4-methoxymethoxy-phenyl) -ethylidenaminooxy] -butyl} Methyl -2- methyl- [1,3] dioxan-2-carboxylate XH NMR: 1.09 (2H, m), 1.34-1.39 (2H, m), 1.51 (3H, s), 1.66-1.71 (2H, m) 2.04 (1H, m), 2.18 (3H, s), 3.40 (2H, t, J = 11.8 Hz), 3.47 (3H, s), 3.83 (3H , s), 3.96 (2H, dd, J = 12.06 and 4.65 Hz), 4.13 (2H, t, J = 6.45 Hz), 5.19 (2H, s), 6.99-7.04 (2H, m) 7.54-7.58 (2H , m) Yield: 47% Example 40 5-. { 4- [1- (4-hydroxy-phenyl) -ethylidenaminooxy] -butyl} Methyl -2- methyl- [1,3] dioxan-2-carboxylate To a solution of 5-. { 4- [1- (4-methoxymethoxy-phenyl) -ethylidenaminooxy] -butyl} Methyl 2-methyl- [1,3] dioxan-2-carboxylate (prepared as in Example 39) (1.5 g) in isopropyl alcohol was added concentrated hydrochloric acid and the reaction mixture was kept under stirring at 50 ° C. C for approximately 20 hours. The reaction mixture was cooled to room temperature and the solvent was evaporated under reduced pressure in a rotary evaporator. Water was added to the residue and extracted with ethyl acetate. The combined organic extract was washed with water and then with brine solution, dried over sodium sulfate and evaporated under reduced pressure on a rotary evaporator. The crude product was run by flash chromatography on silica gel using 15% ethyl acetate in petroleum ether as eluent and 200 mg of the pure product was obtained. XH NMR: 1.04-1.11 (2H, m), 1.32-1.42 (2H, m), 1. 51 (3H, s), 1.63-1.70 (2H, m) 2.04 (1H, m), 2.18 (3H, s), 3.40 (2H, t, J = 11.8 Hz), 3.83 (3H, s), 3.96 ( 2H, dd, J = 12.06 and 4.68 Hz), 4.13 (2H, t, J = 6.42 Hz), 6.81 (2H, dd, J = 6.69 and 2.01 Hz), 7.54 (2H, dd, J = 6.69 and 1.95 Hz ). Performance: 15% Example 41 5-. { 4- [1- (4-methanesulfonyloxy-phenyl) -ethylidenaminooxy] -butyl} Methyl -2- methyl- [1,3] dioxan-2-carboxylate To an ice-cold solution of 5-. { 4- [1- (4-hydroxy-phenyl) -ethylidenaminooxy] -butyl} Methyl 2-methyl- [1,3] dioxan-2-carboxylate (prepared as in Example 40) (200 mg) in anhydrous dichloromethane was added triethylamine (82 mg) and methanesulfonyl chloride (75 mg) and the The reaction mixture was kept under stirring at the same temperature for about one hour. The reaction mixture was diluted with dichloromethane, washed with water, dried over sodium sulfate and evaporated under reduced pressure in a rotary evaporator. The crude product was run by flash chromatography on silica gel using 20% ethyl acetate in petroleum ether as eluent and 200 mg of pure product was obtained. XH NMR: 1.04-1.12 (2H, m), 1.34-1.42 (2H, m), 1.51 (3H, s), 1.56-1.71 (2H, m) 2.04 (1H, m), 2.21 (3H, s), 3. 14 (3H, s), 3.40 (2H, t, J = 11.8 Hz), 3.83 (3H, s), 3.96 (2H, dd, J = 12.06 and 4.68 Hz), 4.16 (2H, t, J = 6.48 Hz), 7.27- 7.29 (2H, m), 7.67-7.70 (2H, m). Performance: 83% Example 42 2-Methyl-5- [4- (1-phenyl-ethylidenaminooxy) -butyl] - [1, 3] dioxan-2-carboxylic acid To a solution of methyl-2-methyl-5- [4- (1 methyl phenyl-ethylidenaminooxy) -butyl] - [1,3] dioxan-2-carboxylate (prepared as in Example 1) (1.38 g) in a mixture of tetrahydrofuran and methanol was added another solution of LiOH.H20 ( 332 mg) in water and the reaction mixture was kept stirring at room temperature for about 18 hours. The solvent was evaporated under reduced pressure, water was added to the residue, acidified 52. 517 with 1N HCl at pH 6 and extracted with ethyl acetate. The combined organic extract was washed with water and then with brine solution, dried over sodium sulfate and evaporated under reduced pressure. The crude product was run by flash chromatography on silica gel using 25% ethyl acetate in hexane as eluent and 1 g of pure product was obtained. XH NMR: 1.1 (2H, m), 1.4 (2H, m), 1.5 (3H, s), 1.7 (2H, m), 2.0 (1H, m), 2.2 (3H, s), 3.4 (2H, t , J = 11.5 Hz), 4.0 (2H, dd, J = 12.0 and 4.5 Hz), 4.1 (2H, t, J = 6.4 Hz), 7.3 (3H, m), 7.6 (2H, m). Yield: 79% The following compounds were prepared by a procedure similar to that described in Example 42 with appropriate variations of reagents, reaction conditions and amounts of reagents.

EXAMPLE 43 5- (4-Benzylideneaminooxy-butyl) -2-methyl- [1,3] dioxan-2-carboxylic acid XH NMR: 1.1 (2H, m), 1.4 (2H, m), 1.5 (3H, s) , 1. 73 (2H, m), 2.0 (1H, m), 3.4 (2H, t, J = 11.6 Hz), 4.0 (2H, dd, J = 11.9 and 4.5 Hz), 4.1 (2H, t, J = 6.4 Hz ), 7.3 (3H, m), 7.5 (2H, m), 8.0 (1H, s). Performance: 96% Example 44 52. 517 2-methyl-5-acid. { 4- [1- (4-trifluoromethyl-phenyl) -ethylidenaminooxy] -butyl} - [1, 3] dioxan-2-carboxylic XH NMR: 1.1 (2H, m), 1.4 (2H, m), 1.5 (3H, s), 1. 7 (2H, m), 2.0 (1H, m), 2.2 (3H, s), 3.4 (2H, t, J = 11.6 Hz), 4.0 (2H, dd, J = 12.0 and 4.7 Hz), 4.1 (2H , t, J = 6.4 Hz), 7. 6 (2H, t, J = 8.2 Hz), 7.7 (2H, d, J = 8.0 Hz). Performance: 97% Example 45 Acid 5-. { 4- [1- (4-fluoro-phenyl) -ethylidenaminooxy] -butyl} -2-methyl- [1,3] dioxan-2-carboxylic XH NMR: 1.1 (2H, m), 1.4 (2H, m), 1.5 (3H, s), 1. 7 (2H, m), 2.0 (1H, m), 2.2 (3H, s), 3.4 (2H, t, J = 11.6 Hz), 4.0 (2H, dd, J = 11.9 and 4.5 Hz), 4.1 (2H , t, J = 6.4 Hz), 7.0 (2H, t, J = 8.6 Hz), 7.6 (2H, m). Performance: 83% Example 46 Acid 5-. { 4- [1- (4-chloro-phenyl) -ethylidenaminooxy] -butyl} -2-methyl- [1,3] dioxan-2-carboxylic acid XH NMR: 1.1 (2H, m), 1.3 (2H, m), 1.5 (3H, s), 1. 7 (2H, m), 2.0 (1H, m), 2.2 (3H, s), 3.5 (2H, t, J = 11.5 Hz), 4.0 (2H, m), 4.1 (2H, t, J = 6.3 Hz ), 7.3 (2H, d, J = 8.5 Hz), 7.6 (2H, d, J = 8.5 Hz). Performance: 79% Example 47 52. 517 Acid 5-. { 4- [1- (4-methanesulfonyl-phenyl) -ethylidenaminooxy] -butyl} -2-methyl- [1,3] dioxan-2-carboxylic XH NMR: 1.1 (2H, m), 1.4 (2H, m), 1.5 (3H, s), 1. 7 (2H, m), 2.0 (1H, m), 2.2 (3H, s), 3.0 (3H, s), 3.4 (2H, t, J = 11.6 Hz), 4.0 (2H, dd, J = 11.9 and 4.4 Hz), 4.2 (2H, t, J = 6.4 Hz), 7.8 (2H, d, J = 8.5 Hz), 7.9 (2H, d, J = 8.5 Hz).

Performance: 80% Example 48 2-Methyl-5- [4- (1-p-tolyl-ethylidenaminooxy) -butyl] - [1, 3] dioxan-2-carboxylic acid XH NMR: 1.07-1.14 (2H, m), 1.33-1.41 (2H, m), 1. 52 (3H, s), 1.64-1.72 (2H, m) 2.05 (1H, m), 2.19 (3H, s), 2. 35 (3H, s), 3.47 (2H, m), 3.99 (2H, dd, J = 12.03 and 4.56 Hz), 4.15 (2H, t, J = 6.45 Hz), 7.16 (2H, d, J = 8.07 Hz ), 7. 52 (2H, d, J = 8.19 Hz). Performance: 22% Example 49 Acid 5-. { 4- [1- (3-Chloro-4-fluoro-phenyl) -ethylidenaminooxy] -butyl} -2-methyl- [1, 3] dioxan-2-carboxylic acid? H NMR: 1.07-1.15 (2H, m), 1.35 (2H, m), 1.56 (3H, s), 1.65-1.71 (2H, m), 2.05 (1H, m), 2.18 (3H, s), 3. 43-3.57 (2H, m), 3.99 (2H, dd, J = 11.48 and 4.56 Hz), 4.16 (2H, t, J = 6.42 Hz), 7.12 (1H, m), 7.47-7.69 (1H, m), 7.70 (1H, dd, J = 7.08 and 2.16 Hz). Performance: 89% 52. 517 Example 50 Acid 5-. { 4- [1- (4-Butyl-phenyl) -ethylidenaminooxy] -butyl} -2-methyl- [1,3] dioxan-2-carboxylic XH NMR: 0.91 (3H, t, J = 7.29Hz), 1.12 (2H, m), 1. 36 (4H, m), 1.56-1.61 (5H, s), 1.69 (2H, m), 2.04 (1H, m), 2.17 (3H, s), 2.61 (2H,, t, J = 7.53 Hz), 3.46 (2H, t, J = 11.46 Hz), 3.99 (2H, dd, J = 11.88 and 4.5 Hz), 4.15 (2H, t, J = 6.33 Hz), 7.16 (2H, d, J = 8.07 Hz), 7.53 (2H, d, J = 8.04 Hz). Performance: 98% Example 51 2-methyl-5-acid. { 4- [1- (4-methylsulfanyl-phenyl) -ethylidenaminooxy] -butyl} - [1, 3] dioxan-2-carboxylic XH NMR: 1.07-1.15 (2H, m), 1.33-1.43 (2H, m), 1. 57 (3H, s), 1.65-1.72 (2H, m) 2.06 (1H, m), 2.19 (3H, s), 2.49 (3H, s), 3.46 (2H, t, J = 11.52 Hz), 3.99 ( 2H, dd, J = 12.06 and 4.68 Hz), 4.15 (2H, t, J = 6.42 Hz), 7.22 (2H, d, J = 8.46 Hz), 7.54-7.57 (2H, d, J = 8.43 Hz). Performance: 76% Example 52 Acid 5-. { 4- [1- (4-ethyl-phenyl) -ethylidenaminooxy] -butyl} -2-methyl- [1,3] dioxan-2-carboxylic acid x NMR: 1.09-1.14 (2H, m), 1.22 (3H, t, J = 7.59 Hz), 1.38 (2H, m), 1.56 (3H, s), 1.64-1.74 (2H, m), 2.05 52. 517 (1H, m), 2.20 (3H, s), 2.63 (2H, q, J = 15.06 and 7.53 Hz), 3.46 (2H, t, J = 10.2 Hz), 3.99 (2H, dd, J = 11.46 and 4.23 Hz), 4.15 (2H, t, J = 6.36 Hz), 7.18 (2H, d, J = 8.07 Hz), 7.54 (2H, d, J = 8.16 Hz). Performance: 91% Example 53 5-. { 4- [1- (3, 4-dimethyl-phenyl) -ethylidenaminooxy] -butyl} -2-methyl- [1,3] dioxan-2-carboxylic acid XH NMR: 1.07-1.14 (2H, m), 1.35-1.42 (2H, m), 1.56 (3H, s), 1.67-1.71 (2H, m ), 2.05 (1H, m), 2.19 (3H, s), 2.26 (3H, s), 2.27 (3H, s), 3.46 (2H, t, J = 10.2 Hz), 3.99 (2H, dd, J = 11.46 and 4.23 Hz), 4.15 (2H, t, J = 6.42 Hz), 7.12 (1H, d, J = 7.83 Hz), 7.32-7.36 (1H, m), 7.60 (1H, m). Performance: 84% Example 54 Acid 5-. { 5- [1- (3, 4-dimethyl-phenyl) -ethylidenaminooxy] -pentyl} -2-methyl- [1,3] dioxan-2-carboxylic acid 1H NMR: 1.05-1.10 (2H, m), 1.28-1.38 (4H, m), 1.56 (3H, s), 1.69 (2H, m), 2.03 (1H, m), 2.19 (3H, s), 2.26 (3H, s), 2.27 (3H, s), 3.45 (2H, t, J = 11.8 Hz), 3.99 (2H, dd, J = 11.96 and 4.53 Hz), 4.15 (2H, t, J = 6.51 Hz), 7.12 (1H, d, J = 7.86 Hz), 7.33 (1H, d, J = 7.98 Hz), 7.41 (1H, s). Performance: 89% 52. 517 Example 55: Acid 5-. { 4- [1- (4-ethoxy-phenyl) -ethylidenaminooxy] -butyl} -2-methyl- [1,3] dioxan-2-carboxylic 1ti NMR: 1.06-1.14 (2H, m), 1.25-1.43 (5H, m), 1.56 (3H, s), 1.68 (2H, m), 2.04 (1H, m), 2.18 (3H, s), 3. 46 (2H, t, J = 11.52 Hz), 3.96-4.08 (4H, m), 4.13 (2H, t, J = 6.39 Hz), 6.86 (2H, d, J = 8.79 Hz), 7.56 (2H, d, J = 8.79 Hz). Performance: 90% Example 56 Acid 5-. { 4- [1- (4-isopropoxy-phenyl) -ethylidenaminooxy] -butyl} -2-methyl- [1,3] dioxan-2-carboxylic acid 1H NMR: 0.86 (2H, m), 1.06-1.24 (8H, m), 1.56 (3H, s), 1.66 (2H, m), 2.04 (1H, m), 2.18 (3H, s), 3.46 (2H, t, J = 10.59 Hz), 3.96 (2H, dd, J = 11.70 and 4.56 Hz), 4.13 (2H, t, J = 6.36 Hz), 4.56 (1H, m), 6.86 (2H, d, J = 8.58 Hz), 7.56 (2H, d, J = 8.58 Hz). Performance: 87% Example 57: Acid 5-. { 4- [1- (4-methoxy-3-methyl-phenyl) -ethylidenaminooxy] -butyl} -2-methyl- [1, 3] dioxan-2-carboxylic acid XH NMR: 1.09-1.14 (2H, m), 1.35-1.43 (2H, m), 1. 56 (3H, s), 1.64-1.74 (2H, m), 2.05 (1H, m), 2.18 (3H, s), 2.22 (3H, m), 3.46 (2H, t, J = 10.32 Hz), 3.84 (3H, s), 3.99 (2H, dd, J = 11.88 and 4.50 Hz), 4.14 (2H, t, J = 6.39 Hz), 52. 517 6.80 (1H, d, J = 8.46 Hz), 7.44 (1H, dd, J = 8.46 and 2.06 Hz), 7.45 (1H, m). Performance: 82% Example 58 2-methyl-5-acid. { 4- [1- (4-phenoxy-phenyl) -ethylidenaminooxy] -butyl} - [1, 3] dioxan-2-carboxylic acid XH NMR: 1.09-1.14 (2H, m), 1.36-1.41 (2H, m), 1.56 (3H, s), 1.65-1.74 (2H, m), 2.05 ( 1H, m), 2.20 (3H, s), 3.46 (2H, m), 3.99 (2H, dd, J = 12.03 and 4.59 Hz), 4.15 (2H, t, J = 6.39 Hz), 6.97-7.035 (4H , m), 7.12 (1H, d, J = 7.35 Hz), 7.33 (2H, m), 7.60 (2H, d, J = 6.81 and 2.01 Hz). Performance: 78% Example 59 Acid 5-. { 4- [1- (3, 4-dimethoxy-phenyl) -ethylidenaminooxy] -butyl} -2-methyl- [1, 3] dioxan-2-carboxylic acid XH NMR: 1.09-1.15 (2H, m), 1.36-1.41 (2H, m), 1.56 (3H, s), 1.67-1.72 (2H, m ) 2.05 (1H, m), 2.19 (3H, s), 3.46 (2H, t, J = 11.58 Hz), 3.89 (3H, s), 3.92 (3H, s), 3.99 (2H, dd, J = 12.06 and 4.50 Hz), 4.15 (2H, t, J = 6.42 Hz), 6.85 (1H, d, J = 8.4 Hz), 7.13 (1H, dd, J = 8.37 and 2.04 Hz), 7.27 (1H, d, J = 2.01Hz). Performance: 81% Example 60 Acid 5-. { 4- [1- (4-isobutyl-phenyl) - 52. 517 ethylidenaminooxy] -butyl} -2-methyl- [1, 3] dioxan-2-carboxylic acid 1H NMR: 0.88 (3H, s), 0.90 (3H, s), 1.09-1.14 (2H, m), 1.38 ((2H, m), 1.56 (3H, s), 1.62 (2H, m), 1.85 (1H, m) 2.01 (1H, m), 2.20 (3H, s), 2.47 (2H, d, J = 7.17 Hz), 3.46 (2H, t , J = 9.48 Hz), 3.99 (2H, dd, J = 12.06 and 4.56 Hz), 4.15 (2H, t, J = 6.45 Hz), 7.12 (2H, d, J = 8.28 Hz), 7.53 (2H, d , J = 8.16 Hz) Yield: 97% Example 61 Acid 5-. { 4- [1- (3-fluoro-4-methoxy-phenyl) -ethylidenaminooxy] -butyl} -2-methyl- [1, 3] dioxan-2-carboxylic acid 1H NMR: 1.07-1.14 (2H, m), 1.33-1.40 (2H, m), 1.56 (3H, s), 1.64-1.73 (2H, m ), 2.05 (1H, m), 2.17 (3H, s), 3.46 (2H, t, J = 11.51), 3.90 (3H, s), 3.99 (2H, dd, J = 12.06 and 4.59 Hz), 4.14 ( 2H, t, J = 6.42 Hz), 6.91 (1H, m), 7.31-7.35 (1H, m), 7.42-7.47 (1H, dd, J = 12.75 and 2.13 Hz). Performance: 90% Example 62 2-Methyl-5- [5- (l-naphthalen-2-yl-ethylidenaminooxy) -pentyl] - [1, 3] dioxan-2-carboxylic acid 1ti NMR: 1.03-1.10 (2H, m), 1.32 -1.40 (4H, m) , 1.55 (3H, s), 1.71 (2H, m), 2.04 (1H, m), 2.32 (3H, s), 3. 49 (2H, t, J = 7.92 Hz), 3.98 (2H, dd, J = 11.64 and 4.38 Hz), 4.21 (2H, t, J = 6.54 Hz), 7.45-7.50 (2H, m), 7.77-7.91 (4H, 52. 517 m), 7.98 (1H, s). Yield: 53% Example 63 2-Methyl-5- [4- (1-naphthalen-2-yl-ethylidenaminooxy) -butyl] - [1, 3] dioxan-2-carboxylic acid XH NMR: 1.09-1.16 (2H, m), 1.36 -1.46 (2H, m), 1. 57 (3H, s), 1.69-1.78 (2H, m) 2.07 (1H, m), 2.33 (3H, s), 3. 47 (2H, t, J = 11.16 Hz), 4.0 (2H, dd, J = 11.82 and 4.68 Hz), 4. 21 (2H, t, J = 6.36 Hz), 7.48 (2H, dd, J = 6.12 and 3.21Hz), 7.78-7.91 (4H, m), 7.99 (1H, m). Performance: 82% Example 64 2-methyl-5-acid. { 4- [1 - (5, 6, 7, 8-tetrahydro-naphthalen-2-yl) -ethylidene-aminooxy] -butyl} - [1, 3] dioxan-2-carboxylic acid 1R NMR: 1.09-1.14 (2H, m), 1.35-1.40 (2H, m), 1.56 (3H, s), 1.64-1.71 (2H, m), 1.76- 1.81 (4H, m), 2.05 (1H, m), 2.18 (3H, s), 2.77 (4H, m), 3.46 (2H, t, J = 11.55 Hz), 3.99 (2H, dd, J = 12.00 and 4.67 Hz), 4.14 (2H, t, J = 6.45 Hz), 7.03-7.06 (1H, d, J = 7.8 Hz), 7.32 (1H, s), 7.34 (1H, s). Performance: 77% Example 65: Acid 5-. { 4- [1- (4-hydroxy-phenyl) -ethylidenaminooxy] -butyl} -2-methyl- [1,3] dioxan-2-carboxyl 52. 517 1 H NMR: 0.85 (2H, m), 1.25 (2H, m), 1.52 (3H, s), 1. 67 (2H, m), 2.04 (1H, m), 2.16 (3H, s), 3.51 (2H, t, J = 11.70 Hz), 3.94 (2H, dd, J = 11.88 and 4.5 Hz), 4.11 (2H, t, J = 6.42 Hz), 6.82 (2H, d, J = 8.7 Hz), 7.49 (2H, m). Performance: 90% Example 66 Acid 5-. { 4- [1- (4-methoxy-phenyl) -ethylidenaminooxy] -butyl} -2-methyl- [1,3] dioxan-2-carboxylic XH NMR: 1.06-1.14 (2H, m), 1.33-1.43 (2H, m), 1. 56 (3H, s), 1.64-1.71 (2H, m) 2.05 (1H, m), 2.18 (3H, s), 3.46 (2H, t, J = 11.52 Hz), 3.82 (3H, s), 3.99 ( 2H, dd, J = 12.06 and 4.68 Hz), 4.13 (2H, t, J = 6.42 Hz), 7.85-6.90 (2H, m), 7.55-7.60 (2H, m). Performance: 94% Example 67 Acid 5-. { 4- [1- (4-methanesulfonyloxy-phenyl) -ethylidenaminooxy] -butyl} -2-methyl- [1,3] dioxan-2-carboxylic XH NMR: 1.13 (2H, m), 1.33-1.43 (2H, m), 1.56 (3H, s), 1.65-1.72 (2H, m) 2.01 (1H, m), 2.19 (3H, s), 3.16 (3H, s), 3.40-3.49 (2H, m), 3.99 (2H, dd, J = 12.06 and 4.68 Hz), 4.18 (2H, t, J = 5.04 Hz), 7.29-7.39 (2H, m), 7.68-7.71 (2H, d, J = 6.78 and 2.01 Hz). Performance: 34% Example 68 52. 517 2-Methyl-5- [4- (l-thiophen-2-yl-ethylidenaminooxy) -butyl] - [1, 3] dioxan-2-carboxylic acid XH NMR: 1.09-1.12 (2H, m), 1.38 ( 2H, m), 1.57 (3H, s), 1.65-1.70 (2H, m) 2.07 (1H, m), 2.33 (3H, s), 3.47 (2H, t, J = 11.37 Hz), 4.0 (2H, dd, J = 11.85 and 4.05 Hz), 4. 13 (2H, t, J = 6.33 Hz), 7.01 (1H, m), 7.19-7.24 (2H, m).

Performance: 85% Example 69: 5- [4- (l-Benzo [l, 3] dioxol-5-yl-ethylidenaminooxy) -butyl] -2-methyl- [1, 3] dioxan-2-carboxylic acid H NMR.1.07-1.14 (2H, m), 1.35-1.43 (2H, m), 1.57 (3H, s), 1.60-1.71 (2H, m), 2.05 (1H, m), 2.17 (3H, s), 3.47 (2H, t , J = 11.15 Hz), 3.99 (2H, dd, J = 12.03 and 4.59 Hz), 4.13 (2H, t, J = 6.39 Hz), 5.97 (2H, s), 6.79 (1H, d, J = 8.16 Hz ), 7.08 (1H, dd, J = 8.1 and 1.77 Hz), 7.20 (1H, d, J = 1.68 Hz). Performance: 84% Example 70: 5- [4- (1-Biphenyl-4-yl-ethylidenaminooxy) -butyl] -2-methyl- [1,3] dioxan-2-carboxylic acid 1H NMR: 1.1 (2H, m), 1.4 (2H) , m), 1.5 (3H, s), 1. 7 (2H, m), 2.0 (1H, m), 2.2 (3H, s), 3.5 (2H, t, J = 11.4 Hz), 4.0 (2H, dd, J = 11.5 and 3.9 Hz), 4.2 (2H, t, J = 6.3 Hz), 7.3 (1H, m), 7.4 (2H, m), 7.6 (4H, m), 7.7 (2H, m). 52. 517 Performance: 74% Example 71 2-Methyl-5- [4- (1-phenyl-pentilideneaminooxy) -butyl] - [1,3] dioxan-2-carboxylic acid XH NMR: 0.93 (3H, t, J = 7.2 Hz), 1.1 ( 2H, m), 1.4 (4H, m), 1.5 (2H, m), 1.57 (3H, s), 1.7 (2H, m), 2.0 (1H, m), 2.7 (2H, t, J = 7.4 Hz), 3.4 (2H, t, J = 11.4 Hz), 4.0 (2H, dd, J = 11.8 and 4.5 Hz), 4.1 (2H, t, J = 6.3 Hz), 7.3 (2H, m), 7.6 (3H,). Performance: 96% Example 72: 5- [4- (1-Benzofuran-2-yl-ethylidenaminooxy) -butyl] -2-methyl- [1, 3] dioxan-2-carboxylic acid 1ti NMR: 1.1 (2H, m), 1.4 (2H) , m), 1.5 (3H, s), 1. 7 (2H, m), 2.0 (1H, m), 2.2 (3H, s), 3.5 (2H, t, J = 11.6 Hz), 4.0 (2H, dd, J = 11.9 and 4.5 Hz), 4.2 (2H , t, J = 6.4 Hz), 6.9 (1H, s), 7.2-7.3 (2H, m), 7.5 (2H, m). Performance: 50% EXAMPLE 73 5- [5- (L-Benzofuran-2-yl-ethylideneaminooxy) -pentyl] -2-methyl- [1,3] dioxan-2-carboxylic acid [epsilon] -tyl NMR: 1.0 (2H, m), 1.4 ( 4H, m), 1.5 (3H, s), 1.7 (2H, m), 2.0 (1H, m), 2.2 (3H, s), 3.45 (2H, t, J = 11.5 Hz), 4.0 (2H, dd, J = 11.7 and 4.4 Hz), 4.2 (2H, t, J = 6.5 Hz), 6.9 52. 517 (1H, s), 7.2-7.3 (2H, m), 7.5 (2H, m). Performance: 95% Example 74 Acid 5-. { 4- [1- (2, 3-dimethyl-benzofuran-6-yl) -ethylidenaminooxy] -butyl} -2-methyl- [1,3] dioxan-2-carboxylic? H NMR: 1.10-1.154 (2H, m), 1.23-1.26 (2H, m), 1.56 (3H, s), 1.66-1.73 (2H, m), 2.04 (1H, m), 2.14 (3H, s), 2.26 (3H, s), 2.38 (3H, s), 3.47 (2H, m), 4.00 (2H, dd, J = 11.5028 and 4.068 Hz ), 4.17 (2H, t, J = 6.13 Hz), 7.35 (lH, d, J = 8.1 Hz), 7.51 (1H, d, J = 8.01 Hz), 7.62 (1H, s). Performance: 30% Example 75 2-methyl-5-acid. { 4- [1- (1-methyl-1H-indol-3-yl) -ethylidene-aminooxy] -butyl} - [1, 3] dioxan-2-carboxylic XH NMR: 1.08-1.23 (2H, m), 1.39-1.44 (2H, m), 1. 55 (3H, s), 1.70-1.77 (2H, m), 2.05 (1H, m), 2.24 (3H, s), 3.46 (2H, t, J = 11.52 Hz), 3.79 (3H, s), 3.97 (2H, dd, J = 11.95 and 4.032 Hz), 4.19 (2H, t, J = 6.39 Hz), 7.17-7.36 (4H, m), 8.27 (1H, d, J = 7.8 Hz). Performance: 90% Example 76 2-Methyl-5- [4- (1-m-tolyl-ethylideneaminooxy) -butyl] - [1, 3] dioxan-2-carboxylic acid XH NMR: 1 acid. 10 (2H, m), 1. 38 (2H, m), 1. 57 (3H, s), 52 517 1.67 (2H, m), 2.0 (1H, m), 2.21 (3H, s), 2.37 (3H, s), 3.47 (2H, t, J = 11.03 Hz), 4.0 (2H, dd, J = 4.5 and 12.03 Hz), 4.16 (2H, t.J = 6.39 Hz), 7.15 - 7.27 (2H, m), 7.4 (2H, m). Performance: 75% Example 77 Acid 5-. { 4- [1- (4-methoxy-phenyl) -propylideneaminooxy] -butyl} -2-methyl- [1,3] dioxan-2-carboxylic acid 1H NMR: 1.1 (5H, m), 1.38 (2H, m), 1.56 (3H, s), 1. 68 (2H, m), 2.05 (1H, m), 2.71 (2H, q, J = 7.57 Hz), 3.46 (2H, t, J = 11.58 Hz), 3.82 (3H, s), 4.0 (2H, dd , J = 4.5 and 11.92 Hz), 4.12 (2H, t.J = 6.33 Hz), 6.89 (2H, d, J = 8.8 Hz), 7.55 (2H, d, J = 8.8 Hz). Performance: 85% Example 78 2-Methyl-5- [4- (1-p-tolyl-propylideneaminooxy) -butyl] - [1,3] dioxan-2-carboxylic acid H NMR: 1.1 (5H, m), 1.38 (2H, m), 1.57 (3H, s), 1.69 (2H, m), 2.0 (1H, m), 2.35 (3H, s), 2.7 (2H, q.J = 7.5 Hz), 3.47 (2H, t, J = 11.58 Hz), 3.98 (2H, dd, J = 4.44 and 11.88 Hz), 4.13 (2H, t J = 6.33 Hz), 7.15 (2H, d, J = 8.0 Hz), 7.52 (2H, d, J = 8.1 Hz). Performance: 91% Example 79 52. 517 2-Methyl-5- [4- (l-pyridin-2-yl-ethylidenaminooxy) -butyl] - [1, 3] dioxan-2-carboxylic acid XH NMR: 0.94 (2H, m), 1.26 (3H, s), 1.28 (2H, m), 1. 57 - 1.72 (3H, m), 2.20 (3H, s), 3.53 (2H, t, J = 11.14Hz), 3.63 (2H, dd, J = 4.9 and 11.18 Hz), 4.12 (2H, t, J = 6.41Hz), 7.39 (1H, m), 7.8 (2H, m), 8.58 (1H, d, J = 4. 66 Hz). Performance: 74% Example 80 2-Methyl-5- [4- (1-pyridin-3-yl-ethylidenaminooxy) -butyl] - [1,3] dioxan-2-carboxylic acid XH NMR: 1.10 (2H, m), 1.41 (2H , m), 1.58 (3H, s), 1. 67 (2H, m), 2.07 (1H, m), 2.22 (3H. S), 3.58 (2H, t, J = 11.58 Hz), 4.0 (2H, dd, J = 4.5 and 11.76 Hz), 4.21 (2H , t, J = 6.2 Hz), 4.46 (1H, bs), 7.4 (1H, t, J = 5.1Hz), 8.0 (1H, d, J = 7.95 Hz), 8.60 (1H, m), 8.95 (lH , s). Performance: 98% Example 81 2-Methyl-5- [4- (1-pyridin-4-yl-ethylidenaminooxy) -butyl] - [1, 3] dioxan-2-carboxylic acid XH NMR: 1.10 (2H, m), 1.37 (2H , m), 1.54 (3H, s), 1.7 (2H, m), 2.0 (1H, m), 2.20 (3H, s), 3.53 (2H, t, J = 11.64 Hz), 3.97 (2H, dd, J = 4.5 and 11.64 Hz), 4.2 (2H, t.J = 6.27Hz), 7.57 (2H, s), 8.62 (2H, s). Performance: 67% 52. 517 Example 82 2-Methyl-5-acid. { 4- [1- (5-methyl-furan-2-yl) -ethylidenaminooxy] -butyl} - [1, 3] dioxan-2-carboxylic acid 1H NMR: 0.57-1.13 (2H, m), 1.37 (2H, m), 1.55 (3H, s), 1.67 (2H, m), 2.00 (1H, m) , 2.01 (3H, s), 2.34 (3H, s), 3.46 (2H,, t, J = 9.27 Hz), 3.99 (2H, dd, J = 11.61 and 4.5 Hz), 4.15 (2H, m), 6.01 (1H, d, J = 2.37 Hz), 6.49 (1H, d, J = 3.18 Hz). Performance: 55%.

Example 83 2-Methyl-5- [4- (1-naphthalen-2-yl-ethylidenaminooxy) -butyl] - [1,3] dioxan-2-carboxylate octyl A mixture of 2-methyl-5- [4] - (1-naphthalene-2-y1-ethylidenaminooxy) -butyl] - [1,3] dioxan-2-carboxylic acid (prepared as in Example 63) (0.9 g), n-octyl bromide (0.6 mL) and carbonate of potassium (0.64 g) in anhydrous dimethyl formamide (10 mL) was kept under stirring at 60 ° C for about 8 hours in an inert atmosphere. The reaction mixture was cooled to room temperature, poured into ice water and extracted with ethyl acetate. The combined organic extract was washed with water, then with brine solution, dried over sodium sulfate and evaporated under reduced pressure. The crude product was run by flash chromatography on silica gel using ethyl acetate 52. 517 ethyl 8% in petroleum ether and 1 g of pure product was obtained. XH NMR: 0.87 (3H, t, J = 6.0 Hz), 1.12 (2H, m), 1. 27-1.43 (12H, m), 1.50 (3H, s), 1.72 (4H, m), 2.04 (1H, m), 2.33 (3H, s), 3.42 (2H, t, J = 11.61 Hz), 3.99 (2H, dd, J = 11.88 and 4.5 Hz), 4.23 (4H, t, J = 1.71 Hz), 7.46-7.51 (2H, m), 7.78-7.92 (4H, m), 7.98 (1H, s). Performance: 86% Example 84 Sodium salt of 2-methyl-5- [4- (1-naphthalen-2-yl-ethylidenaminooxy) -butyl] - [1, 3] dioxan-2-carboxylic acid To a solution of 2-methyl-5-acid - [4- (1-Naphthalen-2-yl-ethylidenaminooxy) -butyl] - [1,3] dioxan-2-carboxylic acid (prepared as in Example 63) (400 mg) in methanol was added sodium methoxide ( 56 mg) and kept stirring at 30 ° C for 0.5 hours. The solvent was evaporated under reduced pressure in a rotary evaporator, the residue was triturated with diethyl ether, filtered and dried under vacuum; 180 mg of the salt was obtained.

EXAMPLE 85 Salt of L-arginine and 2-methyl-5- [4- (1-naphthalen-2-yl-ethylidenaminooxy) -butyl] - [1,3] dioxan-2-carboxylic acid To a suspension of acid 2- methyl-5- [4- (1- 52. 517 naphthalen-2-yl-ethylidenaminooxy) -butyl] - [1,3] dioxan-2-carboxylic acid (prepared as in Example 63) (1 g) in ethanol, was added a solution of L-arginine (451 mg ) in water and the reaction mixture was refluxed for 8 hours. The reaction mixture was cooled to 30 ° C and the solid was separated and vacuum filtered; 400 mg of the salt was obtained.

EXAMPLE 86 Calcium salt of 5- [4- (l-benzofuran-2-yl-ethylidenaminooxy) -butyl] -2-methyl- [1,3] dioxan-2-carboxylic acid 5- [4- (1- benzofuran-2-yl-ethylidenaminooxy) -butyl] -2-methyl- [1,3] dioxan-2-carboxylic acid (prepared as in Example 72) (3 g) was added to a solution of sodium methoxide (prepared by the addition of 184 mg of metallic sodium to 20 mL of anhydrous methanol) and kept stirring for 0.5 hours. To this mixture was added a solution of calcium acetate (632 mg) in water. The solid precipitate was filtered and dried in vacuo; 3 g of salt were obtained. In the same way, the salts listed in Table 1 were prepared by the procedure described in Examples 84 to 86. With similar processes, the salts of the other compounds can also be prepared. 52. 517 Table 1 * The melting points were not corrected and there may be variations of the order of ± 4 ° C. The compounds of the present invention decreased triglycerides, total cholesterol, LDL, VLDL, increased HDL and decreased serum glucose levels. This was demonstrated through experiments with animals in vi tro and also in vivo. A) Demonstration in vi tro of the effectiveness of the compounds: The activities in vi tro of hPPAR a and hPPAR? they were determined according to internal protocols and the results of representative compounds are presented in Table 2 as proof of the efficacy of the new class of compounds described above.

Table 2 52. 517 B) In vivo demonstration of the efficacy of the compounds: i) Serum triglyceride-reducing activity in Swiss albino mice: Swiss albino mice (SAM) were reared in a Zydus bioterio. All animals were subjected to a cycle of 12 hours of light and dark at 25 ± 1 ° C. The animals were fed standard laboratory croquettes (NIN, Hyderabad, India) and free access to water. SAM animals of 20 to 30 g of body weight were used. The protocol approved by the animal research ethics committee (Institutional Animal Ethics Committee) was used. 52. 517 The test compounds were administered orally to Swiss albino mice in a dose of 0.001 to 50 mg / kg / day for 6 days. The compound was administered after mixing 0.25% with CMC (carboxymethylcellulose) or dissolving it in water, if the compound is water-soluble. The control mice were treated with vehicle (0.25% carboxymethylcellulose, 10 ml / kg dose). The blood samples were collected on day 0 and once fed 1 hour after the administration of the drug on day 6 of the treatment. Blood was collected in non-heparinized capillaries and serum analyzed for triglycerides (Wieland, O. Methods of Enzyme Tic analysis, Bergermeyer, H., O., Ed., 1963. 211-214; Trinder, P. Ann. Clin Biochem, 1969. 6: 24-27). The determination of serum triglycerides was done with commercial kits (Zydus-Cadila, Pathline, Ahmedabad, India). Formula for the calculation: The percentage of triglyceride reduction according to the formula was calculated: Percentage of reduction (%) = TT / OT 1 X 100 TC / OC 52. 517 OC = Value of control group on zero day OT = Value of treatment group on zero day TC = Control group on test day TT = Treatment group on test day Table 3 Triglyceride reducing activity in ii) Reductive activity of serum glucose in 52. 517 models of db / db mice The homozygous C57BL / KsJ-db / db mice are obese, hyperglycemic, hyperinsulinemic, and insulin resistant (J. Clin. Invest., 85, 962-967, 1990), while the heterozygotes are skinny and normoglycemic. In homozygous animals, type II human diabetes is closely mimicked when blood sugar levels are not sufficiently controlled. Since this type of model resembles diabetes mellitus human type II, the compounds of the invention were evaluated in this model with respect to their antidiabetic activity. The compounds of the present invention showed reduction activities in glucose and serum triglycerides. In the experiment, male C57 mice were used BL / KsJ-db / db from 8 to 14 weeks of age, with a body weight between 40 and 60 grams, obtained from Jackson Laboratory, USA. The test compounds were either suspended at 0.25% in carboxymethylcellulose or dissolved in water if the compound was water-soluble and administered to the test group, consisting of 6 animals, at a dose of 0.001 mg to 50 mg / kg by oral gavage daily for 6 days. The control group received vehicle (dose of 10 ml / kg). On day 6, one hour after administration 52. 517 of the drug, blood was collected from the retro-orbital sinus and the serum was analyzed for glucose and triglycerides using commercial kits (Zydus-Cadila, Pathline, Ahmedabad, India). The glucose and triglyceride reduction activity of the test compounds was calculated according to the formula: Glucose reducing activity / serum triglycerides (%) = OC = Value of control group on zero day OT = Value of treatment group on zero day TC = Control group on test day TT = Treatment group on test day Table 4 Reductive activity of glucose and serum triglycerides in db / db mice: 52. 517 No adverse effects were observed with any of the compounds of the invention mentioned. The compounds of the present invention exhibited good glucose, lipid and serum cholesterol lowering activity in the experimental animals that were used. These compounds are useful for the evaluation and / or prophylaxis of diseases caused by hyperlipidemia, hypercholesterolemia, hyperinsulinemia, hypergiucemia, for example, NIDDM, cardiovascular diseases, cerebrovascular accident, hypertension, obesity, since these diseases are related to each other. 52. 517

Claims

CLAIMS: 1. New 1,3-dioxancarboxylic acids of general formula (I), its tautomeric form, its stereoisomers, its pharmaceutically acceptable salts, wherein 'A' represents an optionally substituted fused or unfused group selected from aryl, heteroaryl, heterocyclyl groups; ? B 'represents a group (Ci-Cβ) linear or branched alkyl, substituted or unsubstituted; ? m 'represents an integer from 2 to 6; Ri represents a group (C1-C3) alkyl, R2 represents hydrogen, group (C1-C3) alkyl.
2. A compound according to claim 1, wherein the aryl group is selected from a monocyclic, bicyclic or tricyclic aryl group.
3. A compound according to claim 1 or 2, wherein the aryl group is selected from phenyl, naphthyl, tetrahydronaphthyl, indane, biphenyl groups.
4. A compound according to claim 1, wherein the heterocyclyl is selected from aromatic or non-aromatic, mono, bi or tricyclic saturated, partially saturated or unsaturated groups, which 52. 517 containing one or more heteroatoms selected from N, 0, S.
5. A compound according to claim 1 or 4 wherein the heterocyclyl group is selected from pyrrolidinyl, imidazolidinyl, piperidinyl, piperazinyl, morpholinyl, oxazolidinyl, thiazolidinyl, and the like; Examples of partially saturated heterocyclic radicals include dihydrothiophene, dihydropyran, dihydrofuran, dihydrothiazole groups.
6. A compound according to claim 1, wherein the heteroaryl groups are selected from 5- to 8-membered aromatic radicals, which may be fused or unfused and which contain one or more heteroatoms selected from 0, N or S.
7. A compound according to claims 1 or 6, wherein the heteroaryl group is selected from pyridyl, thienyl, furyl, pyrrolyl, oxazolyl, thiazolyl, isothiazolyl, imidazolyl, isoxazolyl, oxadiazolyl, thiadiazolyl, triazolyl, tetrazolyl, benzopyranyl, benzopyranonyl, benzofuranyl, benzothienyl, indolinyl, indolyl, azaindolyl groups. , azaindolinyl, benzodihidrofuranilo, benzodihidrotienilo, pyrazolopyrimidinyl, pirazolopirimidonilo, azaquinazolinyl, azaquinazolinoilo, pyridofuranyl, pyridothienyl, thienopyrimidyl, tienopirimidonilo, quinolinyl, pyrimidinyl, pyrazolyl, 52. 517 quinazolinyl, quinazolonyl, pyrimidonyl, pyridazinyl, triazinyl, benzoxazinyl, benzoxazinonyl, benzothiazinyl, benzothiazinonyl, benzoxazolyl, benzothiazolyl, benzimidazolyl, benzotriazolyl, phthalazinyl, naphthylidinyl, purinyl, carbazolyl, phenothiazinyl, phenoxazinyl.
8. A new compound according to any of the preceding claims, wherein if? A 'is substituted, the substituents may be selected from hydroxyl, oxo, halo, thio, or optionally substituted groups selected from alkyl, haloalkyl, alkoxy, alkoxyalkyl, haloalkoxy, cycloalkyl, alkoxy, cycloalkoxy, aryl, aryloxy, aralkyl, aralkoxy, heteroaryl, heteroaralkyl, heteroaryloxy, acyl, acyloxy, hydroxyalkyl, alkoxyalkyl, aryloxyalkyl, aralkoxyalkyl, alkylthio, thioalkyl, arylthio, alkylsulfonyloxy, sulfenyl derivatives, sulfonyl derivatives.
A compound according to claims 1 or 8, wherein if the substituents of? A 'are also substituted, these substituents may be selected from hydroxyl, oxo, halo, thio, or substituted or unsubstituted groups selected from alkyl, haloalkyl , alkoxy, haloalkoxy, acyl, acyloxy, alkylthio, thioalkyl, alkylsulfonyloxy, alkoxycarbonylamino, derivatives 52. 517 sulfenyl, sulfonyl derivatives.
10. A compound according to any of the preceding claims, preferably selected from: methyl 2-Methyl-5- [4- (1-phenyl-ethylidenaminooxy) -butyl] - [1,3] dioxan-2-carboxylate; 2-Methyl-5- [4- (1-phenyl-pentylideneaminooxy) -butyl] - [1,3] dioxan-2-carboxylic acid methyl ester; 5- (4-Benzylideneaminoxy-butyl) -2-methyl- [1,3] dioxan-2-carboxylic acid methyl; 2-Methyl-5-. { 4- [1- (4-trifluoromethyl-phenyl) -ethylidenaminooxy] -butyl} - [1,3] dioxan-2-carboxylic acid methyl; 5- . { 4- [1- (4-Fluoro-phenyl) -ethylidenaminooxy] -butyl} Methyl -2- [1,3] dioxan-2-carboxylate; 5- . { 4- [1- (Chloro-phenyl) -ethylidenaminooxy] -butyl} Methyl 2 - methyl- [1,3] dioxan-2-carboxylate; 5- (4- [l- (4-Methanesulfonyl-phenyl) -ethylidenaminooxy] -butyl} -2-methyl- [1,3] dioxan-2-carboxylic acid methyl ester (2-methyl-5- [4] - (1-m-tolyl-ethylidenaminooxy) -butyl] - [1, 3] dioxan-) -2-carboxylic acid methyl- 5- {4- [1- (4-Butyl-phenyl) -ethylidenaminoxy] - methyl butyl) -2-methyl- [1, 3] dioxan-2-carboxylate; 2-Methyl-5- [4- (1-p-tolyl-ethylidenaminooxy) -butyl] - 52. 517 [1,3] dioxan-2-carboxylic acid methyl; 2-methyl-5-. { 4- [1- (4-Methylsulfanyl-phenyl) -ethylidenaminooxy] -butyl} - [1,3] dioxan-2-carboxylic acid methyl; 5-. { 4- [1- (4-Ethyl-phenyl) -ethylidenaminooxy] -butyl} Methyl 2 - methyl- [1,3] dioxan-2-carboxylate; 5-. { 4- [1- (4-Ethoxy-phenyl) -ethylidenaminooxy] -butyl} Methyl -2- [1,3] dioxan-2-carboxylate; 5-. { 4- [1- (4-Isopropoxy-phenyl) -ethylidenaminooxy] -butyl} Methyl -2- [1,3] dioxan-2-carboxylate; 2-methyl-5-. { 4- [1- (4-Phenoxy-phenyl) -ethylidenaminooxy] -butyl} - [1,3] dioxan-2-carboxylic acid methyl; 5- . { 4- [1- (4-Isobutyl-phenyl) -ethylidenaminooxy] -butyl} Methyl -2- [1,3] dioxan-2-carboxylate; 5- . { 4- [1- (4-Methoxy-phenyl) -ethylidenaminooxy] -butyl} Methyl -2- [1,3] dioxan-2-carboxylate; 5- [4- (1-Biphenyl-4-yl-ethylidenaminooxy) -butyl] -2-methyl- [1,3] dioxan-2-carboxylic acid methyl ester; 5-. { 4- [1- (3-Chloro-4-fluoro-phenyl) -ethylidene-aminooxy] -butyl} Methyl -2- methyl- [1,3] dioxan-2-carboxylate; 5-. { 4- [1- (3, 4-Dimethyl-phenyl) -ethylidenaminooxy] -butyl} Methyl -2- [1,3] dioxan-2-carboxylate; 5-. { 5- [l- (3, Dimethyl-phenyl) -ethylidene-aminooxy] - 52. 517 pentyl} Methyl -2- [1,3] dioxan-2-carboxylate; 5-. { 4- [1- (4-Methoxy-3-methyl-phenyl) -ethylidenaminooxy] -butyl} Methyl -2- methyl- [1,3] dioxan-2-carboxylate; 5-. { 4- [1- (3, 4-Dimethoxy-phenyl) -ethylidenaminooxy] -butyl} Methyl -2- [1,3] dioxan-2-carboxylate; 5-. { 4- [1- (3-Fluoro-4-methoxy-phenyl) -ethylidenaminooxy] -butyl} Methyl -2- methyl- [1,3] dioxan-2-carboxylate; (5- {4- [1- (4-Methoxy-phenyl) -propylideneaminooxy] -butyl} -2-methyl- [1,3] dioxan-) -2-carboxylic acid methyl ester; . { 2-Methyl-5- [4- (1-p-tolyl-propylideneaminooxy) -butyl] - [1, 3] dioxan} -2-methyl carboxylate; . { 2-Methyl-5- [4- (1-pyridin-2-yl-ethylidenaminooxy) -butyl] - [1, 3] dioxan} -2-methyl carboxylate; . { 2-Methyl-5- [4- (l-pyridin-3-yl-ethylidenaminooxy) -butyl] - [1, 3] dioxan} -2-methyl carboxylate; . { 2-Methyl-5- [4- (l-pyridin-4-yl-ethylidenaminooxy) -butyl] - [1, 3] dioxan} -2-methyl carboxylate; 5- [4- (1-Benzo [1,3] dioxol-5-yl-ethylidenaminooxy) -butyl] -2-methyl- [1,3] dioxan-2-carboxylic acid methyl ester; 2-Methyl-5- [4- (1-thiophen-2-yl-ethylidenaminooxy) -butyl] - [1,3] dioxan-2-carboxylic acid methyl ester; 5- [4- (1-Benzofuran-2-yl-ethylidenaminooxy) -butyl] -2-methyl- [1,3] dioxan-2-carboxylic acid methyl ester; 52. 517 5- [5- (1-Benzofuran-2-yl-ethylidenaminooxy) -pentyl] -2-methyl- [1,3] dioxan-2-carboxylic acid methyl ester; 5-. { 4- [1- (2, 3-Dimethyl-benzofuran-6-yl) -ethylidenaminooxy] -butyl} Methyl -2- methyl- [1,3] dioxan-2-carboxylate; 2-Methyl-5-. { 4- [1- (1-methyl-1H-indol-3-yl) -ethylidene-aminooxy] -butyl} - [1,3] dioxan-2-carboxylic acid methyl; 2-Methyl-5- [5- (1-naphthalen-2-yl-ethylidenaminooxy) -pentyl] - [1,3] dioxan-2-carboxylic acid methyl ester; 2-Methyl-5- [4- (l-naphthalen-2-yl-ethylidenaminooxy) -butyl] - [1,3] dioxan-2-carboxylic acid methyl ester; 2-Methyl-5-. { 4- [1- (5, 6, 7, 8-tetrahydro-naphthalen-2-yl) -ethylidenaminooxy] -butyl} - [1,3] dioxan-2-carboxylic acid methyl; 5-. { 4- [1- (4-Methoxymethoxy-phenyl) -ethylidenaminooxy] -butyl} Methyl -2- [1,3] dioxan-2-carboxylate; 5-. { 4- [1- (4-Hydroxy-phenyl) -ethylidenaminooxy] -butyl} Methyl -2- [1,3] dioxan-2-carboxylate; 5-. { 4- [1- (4-Methanesulfonyloxy-phenyl) -ethylidenaminooxy] -butyl} Methyl -2- methyl- [1,3] dioxan-2-carboxylate; 2-Methyl-5- [4- (1-naphthalen-2-yl-ethylidenaminooxy) -butyl] - [1,3] dioxan-2-carboxylic acid octyl ester; 2-Methyl-5- [4- (1-phenyl-ethylidene-aminooxy) - acid 52. 517 butyl] - [1, 3] dioxan-2-carboxylic acid and its pharmaceutically acceptable salts; 5- (4-Benzylideneaminooxy-butyl) -2-methyl- [1,3] dioxan-2-carboxylic acid and its pharmaceutically acceptable salts; 2-methyl-5-acid. { 4- [1- (4-trifluoromethyl-phenyl) -ethylidenaminooxy] -butyl} - [1, 3] dioxan-2-carboxylic acid and its pharmaceutically acceptable salts; Acid 5-. { 4- [1- (4-fluoro-phenyl) -ethylidenaminooxy] -butyl} -2-methyl- [1,3] dioxan-2-carboxylic acid and its pharmaceutically acceptable salts; Acid 5-. { 4- [1- (4-chloro-phenyl) -ethylidenaminooxy] -butyl} -2-methyl- [1,3] dioxan-2-carboxylic acid and its pharmaceutically acceptable salts; Acid 5-. { 4- [1- (4-methanesulfonyl-phenyl) -ethylidenaminooxy] -butyl} -2-methyl- [1,3] dioxan-2-carboxylic acid and its pharmaceutically acceptable salts; 2-Methyl-5- [4- (1-p-tolyl-ethylideneaminooxy) -butyl] - [1, 3] dioxan-2-carboxylic acid and its pharmaceutically acceptable salts; Acid 5-. { 4- [1- (3-Chloro-4-fluoro-phenyl) -ethylidenaminooxy] -butyl} -2-methyl- [1,3] dioxan-2-carboxylic acid and its pharmaceutically acceptable salts; Acid 5-. { 4- [1- (4-Butyl-phenyl) -ethylidenaminooxy] -butyl} -2-methyl- [1,3] dioxan-2-carboxylic acid and its salts 52. 517 pharmaceutically acceptable; 2-methyl-5-acid. { 4- [1- (4-Methylsulphane-phenyl) -ethylidene-aminooxy] -butyl} - [1, 3] dioxan-2-carboxylic acid and its pharmaceutically acceptable salts; Acid 5-. { 4- [1- (4-ethyl-phenyl) -ethylidenaminooxy] -butyl} -2-methyl- [1,3] dioxan-2-carboxylic acid and its pharmaceutically acceptable salts; Acid -. { 4- [1- (3, 4-dimethyl-phenyl) -ethylidenaminooxy] -butyl} -2-methyl- [1,3] dioxan-2-carboxylic acid and its pharmaceutically acceptable salts; Acid 5-. { 5- [1- (3, 4-dimethyl-phenyl) -ethylidenaminooxy] -pentyl} -2-methyl- [1,3] dioxan-2-carboxylic acid and its pharmaceutically acceptable salts; Acid 5-. { 4- [1- (4-ethoxy-phenyl) -ethylidenaminooxy] -butyl} -2-methyl- [1,3] dioxan-2-carboxylic acid and its pharmaceutically acceptable salts; Acid 5-. { 4- [1- (4-isopropoxy-phenyl) -ethylidenaminooxy] -butyl} -2-methyl- [1,3] dioxan-2-carboxylic acid and its pharmaceutically acceptable salts; Acid 5-. { 4- [1- (4-methoxy-3-methyl-phenyl) -ethylidenaminooxy] -butyl} -2-methyl- [1,3] dioxan-2-carboxylic acid and its pharmaceutically acceptable salts; 2-methyl-5-acid. { 4- [1- (4-phenoxy-phenyl) -ethylidenaminooxy] -butyl} - [1, 3] dioxan-2-carboxylic acid and its pharmaceutically acceptable salts; 52. 517 Acid 5-. { 4- [1- (3, 4-dimethoxy-phenyl) -ethylidene-aminooxy] -butyl} -2-methyl- [1,3] dioxan-2-carboxylic acid and its pharmaceutically acceptable salts; Acid 5-. { 4- [1- (4-Isobutyl-phenyl) -ethylidenaminooxy] -butyl} -2-methyl- [1,3] dioxan-2-carboxylic acid Acid 5-. { 4- [1- (3-fluoro-4-methoxy-phenyl) -ethylidenaminooxy] -butyl} -2-methyl- [1,3] dioxan-2-carboxylic acid and its pharmaceutically acceptable salts; 2-Methyl-5- [5- (1-naphthalen-2-yl-ethylidenaminooxy) -pentyl] - [1, 3] dioxan-2-carboxylic acid and its pharmaceutically acceptable salts; 2-Methyl-5- [4- (1-naphthalen-2-yl-ethylidenaminooxy) -butyl] - [1, 3] dioxan-2-carboxylic acid and its pharmaceutically acceptable salts; 2-methyl-5-acid. { 4- [1 - (5, 6, 7, 8-tetrahydro-naphthalen-2-yl) -ethylidene-aminooxy] -butyl} - [1,3] dioxan-2-carboxylic acid and its pharmaceutically acceptable salts; Acid 5-. { 4- [1- (4-hydroxy-phenyl) -ethylidenaminooxy] -butyl} -2-methyl- [1,3] dioxan-2-carboxylic acid and its pharmaceutically acceptable salts; Acid 5-. { - [1- (4-methoxy-phenyl) -ethylidenaminooxy] -butyl} -2-methyl- [1,3] dioxan-2-carboxylic acid and its pharmaceutically acceptable salts; Acid 5-. { 4- [1- (4-methanesulfonyloxy-phenyl) -ethylidenaminooxy] -butyl} -2-methyl- [1,3] dioxan-2-carboxylic acid 52. 517 and its pharmaceutically acceptable salts; 2-Methyl-5- [4- (1-thiophen-2-yl-ethylideneaminooxy) -butyl] - [1, 3] dioxan-2-carboxylic acid and its pharmaceutically acceptable salts; 5- [4- (l-Benzo [l, 3] dioxol-5-yl-ethylidenaminooxy) -butyl] -2-methyl- [1,3] dioxan-2-carboxylic acid and its pharmaceutically acceptable salts; 5- [4- (1-Biphenyl-4-yl-ethylidenaminooxy) -butyl] -2-methyl- [1,3] dioxan-2-carboxylic acid and its pharmaceutically acceptable salts; 2-Methyl-5- [4- (1-phenyl-pentilideneaminooxy) -butyl] - [1, 3] dioxan-2-carboxylic acid and its pharmaceutically acceptable salts; 5- [4- (1-Benzofuran-2-yl-ethylidenaminooxy) -butyl] -2-methyl- [1, 3] dioxan-2-carboxylic acid and its pharmaceutically acceptable salts; 5- [5- (1-Benzofuran-2-yl-ethylidenaminooxy) -pentyl] -2-methyl- [1, 3] dioxan-2-carboxylic acid and its pharmaceutically acceptable salts; Acid 5-. { 4- [1- (2,3-dimethyl-benzofuran-6-yl) -ethylidenaminooxy] -butyl} -2-methyl- [1,3] dioxan-2-carboxylic acid and its pharmaceutically acceptable salts; 2-methyl-5-acid. { 4- [1- (1-methyl-1H-indol-3-yl) -ethylidene-aminooxy] -butyl} - [1, 3] dioxan-2-carboxylic acid and its pharmaceutically acceptable salts; 52. 517 2-Methyl-5- [4- (1-m-tolyl-ethylidene-aminooxy) -butyl] - [1, 3] dioxan-2-carboxylic acid and its pharmaceutically acceptable salts; Acid 5-. { 4- [1- (4-methoxy-phenyl) -propylideneaminooxy] -butyl} -2-methyl- [1,3] dioxan-2-carboxylic acid and its pharmaceutically acceptable salts; 2-Methyl-5- [4- (l-p-tolyl-propylideneaminooxy) -butyl] - [1, 3] dioxan-2-carboxylic acid and its pharmaceutically acceptable salts; 2-Methyl-5- [4- (1-pyridin-2-yl-ethylidenaminooxy) -butyl] - [1, 3] dioxan-2-carboxylic acid and its pharmaceutically acceptable salts; 2-Methyl-5- [4- (1-pyridin-3-yl-ethylideneaminooxy) -butyl] - [1, 3] dioxan-2-carboxylic acid and its pharmaceutically acceptable salts; 2-Methyl-5- [4- (1-pyridin-4-yl-ethylidenaminooxy) -butyl] - [1, 3] dioxan-2-carboxylic acid and its pharmaceutically acceptable salts; 2-methyl-5-acid. { 4- [1- (5-methyl-furan-2-yl) -ethylidenaminooxy] -butyl} - [1, 3] dioxan-2-carboxylic acid and its pharmaceutically acceptable salts.
A pharmaceutical composition containing compounds of formula (I) or their pharmaceutically acceptable salts according to the preceding claims and a pharmaceutically acceptable carrier, diluent or excipients 52. 517 acceptable.
12. A method to prevent or treat diseases caused by hyperlipidemia, hypercholesterolemia, hyperglycemia, obesity, glucose intolerance, response to leptin, insulin response, diabetic complications, the method is to administer to a patient who needs it, a a non-toxic and effective amount of a compound of formula (I) or its pharmaceutically acceptable salts or a pharmaceutical composition containing it, as defined in any of the preceding claims.
A method according to any of the preceding claims, wherein the disease is type 2 diabetes, glucose intolerance, dyslipidemia, hypertension, obesity, atherosclerosis, hyperlipidemia, coronary artery disease, cardiovascular disorders and other diseases in which the resistance Insulin is the underlying pathophysiological mechanism.
14. A medicament for the treatment of diseases caused by hyperlipidemia, hypercholesterolemia, hypergiucemia, obesity, glucose intolerance, resistance to leptin, insulin resistance, diabetic complications, which contains a compound of formula (I) or its salts pharmaceutically 52. 517 acceptable or a pharmaceutical composition according to any of the preceding claims.
15. A medicament according to claim 14, wherein the disease is type 2 diabetes, glucose intolerance, dyslipidemia, hypertension, obesity, atherosclerosis, hyperlipidemia, coronary artery disease, cardiovascular disorders and other diseases in which the resistance to Insulin is the underlying pathophysiological mechanism.
16. Use of the compounds of formula (I), their pharmaceutical compositions and the medicaments containing them according to any of the preceding claims, as a medicament suitable for the treatment of the diseases set forth in any of the aforementioned claims.
17. A process for preparing compounds of formula (I) according to any of the preceding claims, consisting of: a) reaction of compounds of general formula (II), wherein all symbols are as defined in claim 1 , with compounds of general formula (III), in which all the symbols are as defined in claim 1 and L represents a suitable leaving compound, for example, halogen, mesylate, tosylate, triflate and the like, and R2 represents 52. 517 an alkyl group, to obtain a compound of general formula (I) in which all the symbols are as defined in claim 1 and R2 represents a (C1-C3) alkyl group b) hydrolysis of a compound of general formula (I) wherein R2 is an alkyl group as defined above and all other symbols are as defined above, to obtain another compound of general formula (I) wherein R2 is H and the other symbols are as defined in claim 1. 52. 517