Substituted bicyclic heterocyclic compounds, method for their preparing (variants) and using as agents against obesity and hyperholesterolemia

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to substituted bicyclic heterocyclic compounds of the formula (I): their tautomeric forms, stereoisomers, polymorphous forms, pharmaceutically acceptable salts and pharmaceutically acceptable solvates wherein groups R1, R2, R3 and R4, and groups R5 and R6 when they are bound with carbon atom they represent hydrogen, halogen atom, hydroxy-group, alkyl, alkoxy-group; R5 and R6 as a single group or both can represent also an oxo-group when they are bound with carbon atom; when R5 and R6 are bound with nitrogen atom then they represent hydrogen atom, hydroxy-group or such unsubstituted groups as alkyl, alkoxy-group, aralkyl. X means oxygen or sulfur atom; Ar means phenylene, naphthylene or benzofuryl. Proposed compounds can be used against obesity and hypercholesterolemia. Also, the invention describes methods for preparing compounds, pharmaceutical compositions, method for treatment and using compounds proposed.

EFFECT: valuable medicinal properties of compounds and compositions.

52 cl, 77 ex

 

The technical field to which the invention relates.

The present invention relates to new compounds against obesity and hypercholesterolemia, their derivatives, analogs, tautomeric forms, stereoisomers, polymorphic forms, pharmaceutically acceptable salts, pharmaceutically acceptable solvate and containing pharmaceutically acceptable compositions. In particular, the present invention relates to a new β-aryl-α-oxiclean alkylcarboxylic acids of General formula (I), their derivatives, analogs, tautomeric forms, stereoisomers, polymorphic forms, pharmaceutically acceptable salts, pharmaceutically acceptable solvate and containing pharmaceutically acceptable compositions.

The present invention also relates to a method of obtaining the above new compounds, their analogs, derivatives, tautomeric forms, stereoisomers, polymorphic forms, pharmaceutically acceptable salts, pharmaceutically acceptable solvate and containing pharmaceutically acceptable compositions.

The present invention also relates to new intermediates, processes for their preparation and use in preparation of compounds of formula (I).

Compounds of the present invention reduce the total cholesterol (TC), increase high density lipoprotein (HDL) and lower the LDL the bottom of the Oh density (LDL), that has a positive effect in ischemic heart disease and atherosclerosis.

Compounds of General formula (I) can be used for weight loss and for the treatment and/or prevention of diseases such as hypertension, ischemic heart disease, atherosclerosis, stroke, peripheral vascular disease, and related diseases. These compounds can be used for treatment of familial hypercholesterolemia, hypertriglyceridemia, to reduce the level of atherogenic lipoproteins lipoproteins very low density lipoproteins (VLDL) and LDL. Compounds of the present invention can be applied for the treatment of certain renal diseases including glomerulonephritis, glomerulosclerosis, nephrotic syndrome, hypertensive nephrosclerosis and nephropathy. The compounds of formula (I) can also be used for the treatment and/or prevention of resistance to insulin (type II diabetes), resistance to leptin, disorders of glucose tolerance, dyslipidemia, disorders related to syndrome X hypertension, obesity, resistance to insulin, coronary heart disease and other cardiovascular diseases. These compounds may also be useful as inhibitors alsoreported to improve mental abilities in dementia, in the treatment of diabetic complications, diseases associated with naruseniecell of endothelial cells, psoriasis, polycystic ovarian syndrome (PCOS), inflammatory colitis, osteoporosis, motonishi dystrophy, pancreatitis, arteriosclerosis, retinopathy, xanthomas, inflammation and for the treatment of cancer. Compounds of the present invention can be used in the treatment and/or prophylaxis of the aforementioned diseases in combination/ simultaneously with one or more inhibitors of HMG:COA-reductase, such hypolipidemic/ hypolipoproteinemia means, such as derivatives fibre acid, nicotinic acid, cholestyramine, colestipol (colestipol) and probucol (probucol).

The level of technology

Atherosclerosis other peripheral vascular diseases are the main problems affecting the quality of life of millions of people. Therefore, great attention is paid to the elucidation of the etiology of hypercholesterolemia and hyperlipidemia and the development of effective treatment strategies.

Hypercholesterolemia can be defined as that level of cholesterol in blood plasma, which exceeds the adopted conventionally is called a "normal" level. Recently it was found that the "ideal" level of cholesterol is much lower than "normal" cholesterol levels in the General population, and the risk of coronary heart disease (CHD) increases with increasing cholesterol level above the "optimal" (or "ideal"values. There is a clear ricino-effect relationship between hypercholesterolemia and coronary heart disease, especially in persons with multiple risk factors. Most cholesterol is in the form of cholesterol esters with various lipoproteins, such as low-density lipoprotein (LDL), lipoprotein, intermediate density (BOB), high-density lipoprotein (HDL), and lipoproteins of very low density lipoproteins (VLDL). Research clearly shows that there is an inverse relationship between coronary artery disease and atherosclerosis, on the one hand, and the concentration of HDL-cholesterol in the serum (Stampfer et al., N.Engl. J.Med. 325 (1991) 373-381), and the risk of CHD increases with increasing levels of LDL and lonp.

The disease is usually detected fatty "plaques in the carotid, coronary and cerebral arteries, which are mainly composed of cholesterol and its esters. Miller et al. (Br.Med. J., 282 (1981) 1741-1744) showed that increasing the number of HDL particles can reduce the number of sites of stenosis of the coronary arteries of man, and the high level of HDL-cholesterol may protect against the development of atherosclerosis. Picardo et al. (Arteriosclerosis, 6 (1986) 434-441) showed in vitro that HDL can remove cholesterol from cells. They suggested that HDL can remove excess tissue cholesterol and carry it to the liver (Macikinnon et al., J.Biol. Chem. 261 (1986) 2548-2552). Therefore, tools that increase HDL-cholesterol, will have therapeutic value in the treatment of hypercholesterolemia and coronary heart disease.

Obesity - this disease, which often occurs in rich countries and developing countries and is an important cause of mortality. It is a condition of excessive fat accumulation in the body. Causes of obesity is unclear. It is believed that it has a genetic origin or is caused by some interaction between genotype and environment. Regardless of the cause the result is the deposition of fat caused by an imbalance between the inflow and rhogam energy. Obesity treated with diet, exercise, and appetite suppressant. There is a need for effective therapies to combat this disease, because it can cause coronary heart disease, diabetes, stroke, hyperlipidemia, gout, osteoarthritis, reduced fertility, and many other psychological and social problems.

Another disease that greatly affects the quality of life for large numbers of people in the world is diabetes and insulin resistance. The insulin resistance is the diminished ability of insulin to exert its biological action in a wide range of concentrations. When resistance to insulin the body releases a pathologically large amount of insulin to compensate for this defect, and if not, then the concentration of glucose in the blood increases uncontrollably, h what goes on in diabetes. In developed countries, diabetes is common and is associated with a number of pathologies, including obesity, hypertension, hyperlipidemia (J.din. Invest., 75 (1985) 809-817; N.Engl. J.Med., 317 (1987) 350-357; J.Clin. Endocrinol. Metab., 66 (1988) 580-583; J.Clin. Invest., 68 (1975) 957-969), as well as complications in the kidney (publication of the international application WO 95/21608). Currently there is a growing understanding that insulin resistance and relative hyperinsulinemia contribute to obesity, hypertension, atherosclerosis and diabetes type II. The relationship between insulin resistance and obesity, hypertension and angina has been described as syndrome X, in which insulin resistance pathogenic forms the kernel.

Hyperlipidemia is a major cause of cardiovascular (CVD) and peripheral vascular diseases. High risk of CVD associated with increased LDL (low density lipoprotein) and LEP (very low density lipoprotein), which is observed in hyperlipidemia. CVD risk is increased in those patients who along with hyperlipidemia are intolerant to glucose/insulin resistance. Conducted previously, numerous studies have shown that a decrease in triglycerides and total cholesterol in plasma, especially LDL and lonp, and increase HDL-cholesterol contribute to the prevention of cardiovascular diseases.

Receptors, aktivere is haunted by proliferation peroxisome (PPAR), included in the superfamily of nuclear receptors. It is established that gamma isoforms of PPAR (PPARγ) participates in the regulation of differentiation of adipocytes (Endocrinology, 135 (1994) 798-800) and energy homeostasis (Cell 83 (1995) 803-812), whereas alpha-isoforms (PPARα) participates in the oxidation of fatty acids (Trend. Endocrin. Metab., 4 (1993) 291-296) and thereby causes a decrease in the level of free fatty acids in plasma (Current Biol, 5 (1995) 618-621). It was found that agonists of PPARα useful in the treatment of obesity (WO 97/36579). Recently it became known that there is a synergism between the molecules, which simultaneously agonists of PPARα and PPARγand it is assumed that they will be useful in the treatment of syndrome X (WO 97/25042). Similar synergism was observed between sensitization insulin (agonist of PPARγ) and inhibitor of HMG:COA-reductase, which can be useful for the treatment of atherosclerosis and xanthoma (EP 0 753 298).

It is known that PPARγ plays an important role in the differentiation of adipocytes (Cell 87 (1996) 377-389). Activation of PPAR ligands can cause a complete terminal differentiation (Cell 79 (1994) 1147-1156), including the cessation of the cell cycle. Some cells continuously Express PPARγand activation of this nuclear receptor agonists of PPARγ stimulates terminal differentiation of the precursors of adipocytes and causes morphological and molecular treason is Oia, characteristic of more differentiated, less malignant state (Molecular Cell, (1998) 465-470; Carcinogenesis, (1998) 1949-53; Proc. Natl. Acad. Sci., 94 (1997) 237-241), and inhibits the expression of the cancerous tissue of the prostate (Cancer Research, 58 (1998) 3344-3352). This can be useful in the treatment of some cancers expressing PPARy, and cause not toxic chemotherapy.

Resistance to leptin is a state, when the target cell is not able to respond to latinovic signal. This can lead to obesity due to excessive food intake and reduce energy consumption and to cause disturbances of glucose tolerance, type II diabetes, cardiovascular disease and other related complications. Kallen et al. (Proc. Natl. Acad. Sci (1996) 93, 5793-5796) reported that sensitization insulin, Verano, can act through the expression of PPAR agonist, thereby reducing the concentration of leptin in the plasma. However, recently it was reported that compounds with properties sensitizaters insulin, also have activity of sensitizatio leptin. They reduce the concentration of leptin in the blood, improving the response of target cells to leptin (WO 98/02159).

It was reported that some β-aryl-α-hydroxypropionate acid, their derivatives and analogues useful in the treatment of hyperglycemia and hypercholesterolemia. Some of these compounds are described in PR is destoyed the prior art, below:

i) In U.S. patent No. 5306726 and WO 91/19702 revealed several derivatives of 3-aryl-2-hydroxypropionic acid of General formula (IIa) and (IIb) as hypolipidemic and hypoglycemic agents:

Examples of these compounds represented by the formulas (IIc) and (IId):

ii) In international publications WO 95/03038 and WO 96/04260 disclosed compounds of the formula (IIe):

where Ramean 2-benzoxazolyl or 2-pyridyl and Rbmeans CF2CH2Och3or CH3. A typical example is (S)-3-[4-[2-[N-(2-benzoxazolyl)-N-methylamino]ethoxy]-phenyl]-2-(2,2,2-trichoroethane)propanoic acid (IIf):

iii) In international publications WO 94/13650, WO 94/01420 and WO 95/17394 disclosed compounds of General formula (IIg):

where a1means an aromatic heterocycle, And2- substituted benzene ring and a3- the remainder of the formula (CH2)m-CH-(OR1), in which R1means alkyl group, m is an integer, X is substituted or unsubstituted N, Y represents C=O or C=S, R2means OR3where the group R3is alkyl, aralkyl or aryl, a n is an integer from 2 to 6.

The example that the compounds represented by formula (IIh):

in) In U.S. patent No. 5227490 disclosed compounds of General formula (IIi):

where R1can independently mean (C1-C6)alkyl, aryl(C4-C10)alkyl, aryl, carboxy, (C1-C6)alkoxy, carboxy(C0-C6)alkyl, hydroxy(C0-C6)alkyl, (C1-C4)alkylsulfonyl(C0-C6)-alkyl, (C0-C4)alkylamino(C0-C6)alkyl, aryl(C0-C10)alkylamino(C0-C6)alkyl, (C2-C10)-acylamino(C0-C6)alkyl, (C1-C4)carbalkoxy(C0-C6)alkyl, or halogen atom; R2can mean hydrogen, halogen, hydroxyl, (C1-C6)alkyloxy, aryl(C0-C4)alkyl, aryl(C0-C6)-alkyloxy or (C1-C6)alkyl, where the alkyl group is either unsubstituted or substituted by one or more groups selected from hydroxyl, (C1-C4)alkyloxy, amino(C1-C10)alkylsulphonyl, aryl(C0-C10)alkylsulphonyl, aryl(C0-C10)alkylcarboxylic, (C1-C6)alkylsulfonyl, aryl(C0-C6)alkylsulfonyl, (C1-C6)alkylsulfonyl, aryl-(C0-C10)alkylsulfonyl, (C1-C10)allyloxycarbonyl, and the silt ( 0-C6)alkylamine, aryl(C0-C6)alkylcarboxylic, amine, carboxy, aryl, carbonyl-P or SO2P, where P means one L - or D-amino acid or a sequence of 2-4 L - or D-amino acids connected by amide bond; or R2means carboxyl, (C1-C6)alkyl-carbonyl, aryl(C1-C10)alkylaryl, (C1-C6)allyloxycarbonyl(C1-C6)alkyl, (C1-C6)alkylaminocarbonyl(C1-C6)alkyl, aryl(C0-C6)alkylaminocarbonyl(C1-C6)alkyl, aryl(C0-C6)allyloxycarbonyl(C1-C6)alkyl, (C1-C6)alkoxycarbonyl or aryl(C0-C6)allyloxycarbonyl provided that they may be the same or different, when on the same carbon atom is more than one group R2; R3means hydrogen, (C1-C6)alkyl or aryl(C1-C10)alkyl; Z represents NR4R5where R4and R5independently mean hydrogen, (C1-C6)alkyl or aryl(C1-C10)alkyl, and these alkyl group or unsubstituted or substituted (C1-C4)alkyloxy, carboxy(C0-C6)alkyl or hydroxyl group, or halogen, or Z represents a 4-9-membered mono - or bicyclic calcev the th system, containing 1, 2 or 3 heteroatoms selected from N, O or S, which may be unsubstituted or substituted, R4, R5or

Y means (C1-C10)alkyl, either unsubstituted or substituted by one or more groups selected from R4or R5; or Y means (C4-C8)cycloalkyl, aryl, (C0-C3)alkyl-aryl(C0-C3)alkyl, (C0-C3)alkylaryl(C0-C3)alkylsulphonyl, (C0-C3)alkylaryl(C0-C3)alkyl-carboxamido, (C0-C3)alkylsilane(C0-C3)alkyl, (C0-C3)alkyloxy(C0-C6)alkyl,

or -(CH2)m-Q-(CH)nwhere Q means2-C8-membered heterocyclic ring containing 1, 2 or 3 heteroatoms selected from N, O and S, which may be unsubstituted or substituted oxo-, diography or (C1-C6)alkyl, a m and n are integers 0, 1, 2 or 3;

X represents O, S, SO, SO2WITH, -NR4CO, CONR4-, -CH2-, -CH=CH-, -C=C-, -NR4CS-, -CSNR4-SO2NR4- or-NR4SO2.

An example of these compounds is represented by formula (IIj):

Somnos the ü inventions

With the aim of developing new compounds to reduce cholesterol and body weight, have a positive effect in the treatment and/or prevention of diseases associated with increased levels of lipids, atherosclerosis, coronary heart disease, syndrome X, impaired glucose tolerance, insulin resistance, including leading to type II diabetes and its complications for the treatment of diseases and pathophysiological mechanism which is resistance to insulin, and for the treatment of hypertension, with greater efficiency, activity and less toxicity, we focused our research on the development of new compounds effective in the treatment of the above diseases. Work in this direction has led to compounds having General formula (I).

Accordingly, the main object of the present invention to provide a new β-aryl-α-oxiclean alkylcarboxylic acids, their derivatives, analogs, tautomeric forms, stereoisomers, polymorphic forms, pharmaceutically acceptable salts, pharmaceutically acceptable solvate, and pharmaceutical compositions containing them or their mixtures.

Another objective of the present invention to provide a new β-aryl-α-oxiclean alkylcarboxylic acids, their derivatives, analogs, tautomeric forms, stereoisomers is s, polymorphic forms, pharmaceutically acceptable salts, pharmaceutically acceptable solvate, and pharmaceutical compositions containing them or their mixtures having properties agonists of PPARα and/or PPARγand optionally inhibiting HMG:COA-reductase, along with the properties of agonists of PPARα and/or PPARγ.

The next task of the present invention to provide a new β-aryl-α-oxiclean alkylcarboxylic acids, their derivatives, analogs, tautomeric forms, stereoisomers, polymorphic forms, pharmaceutically acceptable salts, pharmaceutically acceptable solvate, and pharmaceutical compositions containing them or their mixtures having a high activity and not having a toxic effect or provide weak toxic effect.

Another objective of the present invention is a method of obtaining new β-aryl-α-oxiclean alkylcarboxylic acids of the formula (I), their derivatives, analogs, tautomeric forms, stereoisomers, polymorphic forms, pharmaceutically acceptable salts and pharmaceutically acceptable solvate.

The next task of the present invention to provide pharmaceutical compositions containing the compounds of formula (I), their analogs, derivatives, tautomers, stereoisomers, polymorphic form, a salt, a solvate, or a mixture thereof together with choosing the appropriate media solvents, diluents and other media, which are usually used in the manufacture of such compositions.

Another object of the present invention to provide a new intermediate compounds, method of their production and use in the process of obtaining β-aryl-α-oxiclean alkylcarboxylic acids of the formula (I), their derivatives, analogs, tautomers, stereoisomers, polymorphic forms, salts and pharmaceutically acceptable solvate.

Detailed description of the invention

β-Aryl-α-oxiclean propionic acid, their derivatives and analogues according to the invention have the General formula (I):

in which groups R1, R2, R3, R4group and R5and R6when they are connected with the carbon atom may be the same or different and represent hydrogen, halogen, hydroxy, nitro, cyano, formyl or unsubstituted or substituted groups as alkyl, cycloalkyl, alkoxy, cycloalkene, aryl, aryloxy, aralkyl, Alcoxy, heterocyclyl, heteroaryl, heteroalkyl, heteroaromatic, heteroaromatic, acyl, acyloxy, amino, acylamino, monoalkylamines, dialkylamines, arylamino, aralkylamines, alkoxycarbonyl, aryloxyalkyl, arelaxation, alkylthio, alkoxycarbonyl, aryloxypropanolamine, alcoxycarbenium, and the e carboxylic acid or its derivatives or sulfonic acid or its derivatives; R5and R6one, or both, can also be oxoprop when they are linked to the carbon atom; in the case when R5and R6linked to the nitrogen atom, they represent a hydrogen, hydroxyl, formyl or unsubstituted or substituted groups as alkyl, cycloalkyl, alkoxy, cycloalkene, aryl, aralkyl, heterocyclyl, heteroaryl, heteroalkyl, acyl, acyloxy, amino, acylamino, monoalkylamines, dialkylamines, arylamino, aralkylamines, aryloxy, Alcoxy, heteroaromatic, heteroaromatic, alkoxycarbonyl, aryloxyalkyl, arelaxation, alkylthio, as well as derivatives of carboxylic acids or derivatives of sulfonic acids; x is the heteroatom selected from oxygen, sulfur or NR11where R11means hydrogen or a unsubstituted or substituted group as alkyl, cycloalkyl, aryl, aralkyl, acyl, alkoxycarbonyl, aryloxyalkyl or arelaxation; Ar denotes unsubstituted or substituted divalent, unfused (individual) or condensed, aromatic or heterocyclic group; R7means a hydrogen atom, hydroxyl, alkoxy, halogen, lower alkyl, unsubstituted or substituted aralkyl, or forms a bond with a neighboring group, R8; R8means hydrogen, hydroxyl, alkoxy, halogen, lower alkyl, acyl, unsubstituted or C is displaced aralkyl, or forms a bond with a neighboring group, R7; R9means hydrogen or a unsubstituted or substituted group as alkyl, cycloalkyl, aryl, aralkyl, alkoxycarbonyl, aryloxyalkyl, alkylaminocarbonyl, allumination, acyl, heterocyclyl, heteroaryl or heteroalkyl; R10means hydrogen or a unsubstituted or substituted group as alkyl, cycloalkyl, aryl, aralkyl, heterocyclyl, heteroaryl or heteroalkyl; Y represents oxygen or NR12where R12represents hydrogen, alkyl, aryl, hydroxyalkyl, aralkyl, heterocyclyl, heteroaryl or heteroalkyl; R10together with R12may form a 5 - or 6-membered cyclic structure containing carbon atoms and at least one nitrogen atom and optionally one or two other heteroatoms selected from oxygen, sulfur or nitrogen; port group -(CH2)n-(O)m- can join via the nitrogen atom or via a carbon atom; n is an integer from 1 to 4, a m is an integer of 0 or 1.

Group R1-R4group and R5and R6when they are joined together with the carbon atom, preferably represent hydrogen, halogen atom such as fluorine, chlorine, bromine or iodine; hydroxyl, cyano, nitro, formyl; substituted or unsubstituted (C1-C12)alkyl, especially linear or branched(C 1-C10)alkyl, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, t-butyl, n-pentyl, isopentyl, hexyl, heptyl, octyl etc.; cyclo(C3-C6)alkyl, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, etc. and cycloalkyl may be substituted; and (C1-C6)alkoxygroup, such as methoxy, ethoxy, propyloxy, bucalossi, isopropoxy etc. and alkoxygroup may be substituted; cyclo-(C3-C6)alkoxygroup, such as cyclopropylamine, cyclobutylamine, cyclopentyloxy, cyclohexyloxy etc. and cycloalkylation may be substituted; aryl, such as phenyl, naphthyl and so on, and aryl may be substituted; alloctype, such as phenoxy, naphthyloxy etc. and alloctype may be substituted; aralkyl, such as benzyl, phenethyl,6H5CH2CH2CH2naphthylmethyl etc. and aralkyl may be substituted, and represent such a group as CH3With6H4CH2Hal-C6H4CH2CH3OS6H4CH2CH3OS6H4CH2CH2etc.; urlcategory - benzyloxy, penetrate, naphthalenyloxy, phenylpropoxy etc. and urlcategory may be substituted; heterocyclyl, such as aziridinyl, pyrrolidinyl, morpholinyl, piperid the Nile, piperazinil etc. and heterocyclyl may be substituted; heteroaryl, such as pyridyl, thienyl, furyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, oxadiazolyl, tetrazolyl, benzopyranyl, benzofuran etc. and heteroaryl may be substituted; heteroaryl, such as furanosyl, pyridylmethyl, oxazolyl, oxazolyl etc. and heteroaryl may be substituted; heteroaromatic or heteroaromatic in which heteroaryl and heteroalkyl have some higher values and may be substituted; acyl, such as acetyl, propionyl, benzoyl, etc. and acyl may be substituted; alloctype, such as Oocme, OOCEt, OOCPh etc., and it may be substituted; allmenalp, such as NHCOCH3, NHCOC2H5, NHCOC3H7, NHCOC6H5and so on, and it may be substituted; monoalkylamines, such as NHCH3, NHC2H5, NHC3H7, NHC6H13and so on, and it may be substituted; dialkylamino, such as N(CH3)2, NCH3(C2H5), N(C2H5)2and so on, and it may be substituted; killingray, such as HNC6H5, NCH3(C6H5), NHC6H4CH3, NHC6H4Hal and so on, and it may be substituted; aralkylamines, such as6H CH2NH6H5CH2CH2NH6H5CH2NCH3and so on, and it may be substituted; an amino group; alkoxycarbonyl, such as methoxycarbonyl, etoxycarbonyl etc. and it may be substituted; aryloxyalkyl, such as phenoxycarbonyl, naphthalocyanines etc. and aryloxyalkyl may be substituted; arelaxation, such as benzyloxycarbonyl, ventilatsioonil, naphthylenediamine etc. and it may be substituted; and (C1-C6)allylthiourea, which may be substituted; alkoxycarbonyl, such as NHCOOC2H5, NHCOOCH3and so on, and it may be substituted; aryloxypropanolamine, such as NHCOOC6H5, NCH3SOOS6H5That NC2H5COOC6H5, NHCOOC6H4CH3, NHCOOC6H4Och3and so on, and it may be substituted; alcoxycarboxylates, such as NHCOOCH2C6H5, NHCOOCH2CH2With6H5N(CH3)COOCH2C6H5N(C2H5)SOON2With6H5, NHCOOCH2C6H4CH3, NHCOOCH2With6H4OCH3and so on, and it may be substituted; carboxylic acid or its derivatives such as amides type CONH2, CONHMe, CONMe2, CONHEt, CONE 2, CONHPh, etc. and they may be substituted; sulfonic acid or its derivatives, such as the SO2NH2, SO2NHMe, SO2NMe2, SO2NHCF3and so on, and they can be replaced. R5and R6one, or both, can also be oxoprop when they are attached to the carbon atom.

When the group R1-R4group and R5and R6if they are connected with the carbon atom are substituted, the substituents can be halogen, hydroxyl, nitro, tigroup or such unsubstituted or substituted groups as alkyl, cycloalkyl, alkoxy, cycloalkene, aryl, aralkyl, aryloxy, Alcoxy, alkoxyalkyl, aryloxyalkyl, alcoxialchil, heterocyclyl, heteroaryl, heteroalkyl, acyl, acyloxy, hydroxyalkyl, amino, acylamino, arylamino, aminoalkyl, alkoxycarbonyl, alkylamino, allylthiourea, as well as carboxylic acid or its derivatives, or sulfonic acid or its derivatives. These groups are defined above.

Preferred substituents for R1-R6are: the Halogens - fluorine, chlorine or bromine; alkyl groups methyl, ethyl, isopropyl, n-propyl, n-butyl; cycloalkyl groups - cyclopropyl; aryl groups phenyl; Uralkalij groups - benzyl; and (C1-C3)alkoxy, benzyloxy, hydroxyl, acyl and alloctype.

R 5and R6when they are joined together with the nitrogen atom, may represent hydrogen, hydroxyl, formyl; substituted or unsubstituted (C1-C12)alkyl, especially linear or branched (C1-C6)alkyl, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, t-butyl, n-pentyl, isopentyl, hexyl, etc.; and (C1-C6)alkoxygroup, such as methoxy, ethoxy, propyloxy, bucalossi, isopropoxy etc., and it may be substituted; cyclo(C3-C6)alkyl, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, etc. and cycloalkyl may be substituted; cyclo(C3-C6)alkoxygroup, such as cyclopropylamine, cyclobutylamine, cyclopentyloxy, cyclohexyloxy etc. and cycloalkylation may be substituted; aryl group such as phenyl, naphthyl and so on, and aryl may be substituted; aralkyl, such as benzyl, phenethyl,6H5CH2CH2CH2naphthylmethyl etc. and kalkilya group may be substituted and represents CH3With6H4CH2Hal-C6H4CH2CH3OS6H4CH2CH3OS6H4CH2CH2etc.; alloctype, such as phenoxy, naphthyloxy etc. and alloctype may be substituted; urlcategory, t is such as benzyloxy, penetrate, naphthalenyloxy, phenylpropoxy etc. and urlcategory may be substituted; heterocyclyl, such as aziridinyl, pyrrolidinyl, morpholinyl, piperidinyl, piperazinil etc. and heterocyclyl may be substituted; heteroaryl group such as pyridyl, thienyl, furyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, oxadiazolyl, tetrazolyl, benzopyranyl, benzofuran etc. and heteroaryl may be substituted; heteroaryl, such as furanosyl, pyridylmethyl, oxazolyl, oxazolyl etc. and heteroaryl may be substituted; heteroaromatic or heteroaromatic in which heteroaryl and heteroaryl have the meanings defined earlier and may be substituted; acyl group such as acetyl, propionyl, benzoyl, etc. and acyl may be substituted; alloctype, such as Oocme, OOCEt, OOCPh etc. which may be substituted; monoalkylamines, such as NHCH3, NHC2H5, NHC3H7, NHC6H13etc. which may be substituted; dialkylamino, such as N(CH3)2, NCH3(C2H5), N(C2H5)2etc. which may be substituted; allmenalp, such as NHCOCH3, NHCOC2H5, NHCOC3H7, NHCOC6H5etc. which may be substituted; killingray such as HNC 6H5, NCH3(C6H5), NHC6H4CH3, NHC6H4-Hal, etc. which may be substituted; aralkylamines, such as6H5CH2NH6H5CH2CH2NH6H5CH2NCH3etc. which may be substituted; alkoxycarbonyl, such as methoxycarbonyl, etoxycarbonyl etc. which may be substituted; aryloxyalkyl, such as phenoxycarbonyl, naphthalocyanines etc. which may be substituted; arelaxation, such as benzyloxycarbonyl, ventilatsioonil, naphthylenediamine etc. which may be substituted; and (C1-C6)allylthiourea, which may be substituted; carboxylic acid derivatives such as amides type CONH2, CONHMe, CONMe2, CONHEt, CONEt2, CONHPh and so on, and these derivatives may be substituted; sulfonic acid derivatives, such as SO2NH2, SO2NHMe, SO2NMe2, SO2NHCF3and so on, and these derivatives can be substituted.

When the group R5and R6connected to the nitrogen atom are substituted, preferred substituents are halogen, such as fluorine or chlorine, hydroxyl, acyl, acyloxy or amino group. These groups are defined above.

X can be an oxygen, sulphur or the group is in NR 11preferably oxygen or sulfur. R11can represent hydrogen, (C1-C6)alkyl group such as methyl, ethyl, propyl, etc., (C3-C6)cycloalkyl group, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, etc., aryl group such as phenyl, naphthyl, etc., aracelio group, such as benzyl, phenethyl, etc., acyl group such as acetyl, propanol, butanol, benzoyl, etc., (C1-C6)alkoxycarbonyl, such as methoxycarbonyl, etoxycarbonyl etc., aryloxyalkyl, such as phenoxycarbonyl, CH3OS6H4CCA, Hal-C6H4OCO, CH3With6H4CCA, naphthalocyanines etc., arelaxation, such as benzyloxycarbonyl, ventilatsioonil and so on; these groups may be substituted or unsubstituted. When R11is a substituted group, the Deputy may be halogen, optionally halogenated lower alkyl, hydroxyl, and optionally halogenated (C1-C3)alkoxygroup. These groups are defined above.

Preferably, Ar represents a substituted or unsubstituted group, which may be a divalent phenylene, naftilan, pyridyl, chinoline, benzofuran, dihydrobenzofuran, benzopyranyl, dihydrobenzofuranyl, indolyl, indolinyl, isoindolyl, azaindole the sludge, pyrazolyl, benzothiazolyl, benzoxazolyl etc. the Group Ar may be substituted by linear or branched, optionally halogenated (C1-C6)alkyl, optionally halogenated (C1-C3)alkoxygroup, halogen, acyl, amino, acylamino, diography or carboxyl or sulfonyloxy groups and their derivatives. The substituents are defined as for R1-R4.

More preferably, the group Ar represents a substituted or unsubstituted divalent phenylene, naftilan, benzofuran, indolyl, indolinyl, chinoline, isoindolyl, isoindolines, benzothiazolyl or benzoxazolyl.

Most preferably, the group Ar represents a divalent phenylene, naftilan or benzofuran, which can be substituted by alkyl, haloalkyl, methoxy - or haloalkoxy.

R7can be a hydrogen, hydroxyl, lower alkyl, such as methyl, ethyl or propyl, (C1-C3)alkoxygroup, such as methoxy, ethoxy, propoxy, etc., halogen atom, such as fluorine, chlorine, bromine or iodine, aralkyl, such as benzyl, phenethyl, etc.,

which may be unsubstituted or substituted, or R7together with R8forms a chemical bond. The Deputy may be halogen, hydroxyl or an alkyl group.

R8can be a hydrogen, hydroxyl, lower alkyl, such as methyl, ethyl or propyl, (C1-C3)alkoxygroup, such as methoxy, ethoxy, propoxy, etc., halogen atom, such as fluorine, chlorine, bromine or iodine, (C2-C10)acyl, such as acetyl, propanol, butanol, pentanol, benzoyl, etc., aralkyl, such as benzyl, phenethyl, etc. which may be unsubstituted or substituted, or R8together with R7forms a chemical bond. The Deputy may be halogen, hydroxyl or an alkyl group.

The group R9can represent hydrogen, linear or branched (C1-C16)alkyl, preferably (C1-C12)alkyl, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, pentyl, hexyl, octyl etc., and the alkyl group may be substituted; and (C3-C7)cycloalkyl, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, etc. and cycloalkyl group may be substituted; aryl, such as phenyl, naphthyl, etc. and aryl group may be substituted; aralkyl, such as benzyl, phenethyl, etc. in which the alkyl part can contain atoms (C1-C6), and kalkilya group may be substituted; heteroaryl, such as pyridyl, thienyl, pyrrolyl, furyl, etc. and heteroaryl group may be substituted; heteroaryl, such as furanosyl, pyridine the sludge, oxazolyl, oxazolyl etc. and heteroalkyl group may be substituted; heterocyclyl, such as aziridinyl, pyrrolidinyl, piperidinyl etc. and heterocyclyl group may be substituted; a linear or branched (C2-C16)-acyl group such as acetyl, propanol, butanol, benzoyl, octanoyl, decanoyl etc. which may be substituted; and (C1-C6)alkoxycarbonyl, such as methoxycarbonyl, etoxycarbonyl etc. and alkoxycarbonyl group may be substituted; aryloxyalkyl, such as phenoxycarbonyl, naphthalocyanines etc., and the aryl part can be substituted; and (C1-C6)alkylaminocarbonyl, and the alkyl part may be substituted; allumination, such as PhNHCO, naphthaleneboronic etc., and the aryl part can be substituted. The Deputy may be halogen, hydroxyl, nitro-group or an unsubstituted or substituted group as alkyl, cycloalkyl, alkoxy, cycloalkene, aryl, aralkyl, alcoxialchil, heterocyclyl, heteroaryl, heteroalkyl, acyl, acyloxy, hydroxyalkyl, amino, acylamino, arylamino, aminoalkyl, aryloxy, Alcoxy, alkoxycarbonyl, alkylamino, alkoxyalkyl, aryloxyalkyl, alkylthio, thioalkyl, as well as carboxylic acid or its derivative, or sulfonic acid or its derivatives is the same. The substituents defined above.

The group R1can represent hydrogen, linear or branched (C1-C6)alkyl, preferably (C1-C12)alkyl, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, pentyl, hexyl, octyl etc., and the alkyl group may be substituted; and (C3-C7)cycloalkyl - cyclopropyl, cyclopentyl, cyclohexyl, etc. and cycloalkyl group may be substituted; aryl, such as phenyl, naphthyl, etc. and aryl group may be substituted; heteroaryl, such as pyridyl, thienyl, pyrrolyl, furyl, etc. and heteroaryl group may be substituted; heteroaryl, such as furanosyl, pyridylmethyl, oxazolyl, oxazolyl etc. and heteroalkyl group may be substituted; aralkyl, such as benzyl, phenethyl, etc. and kalkilya group may be substituted; heterocyclyl, such as aziridinyl, pyrrolidinyl, piperidinyl etc. and heterocyclyl group may be substituted. Deputy in R10can be halogen, hydroxyl, nitro-group or an unsubstituted or substituted group as alkyl, cycloalkyl, alkoxy, cycloalkene, aryl, aralkyl, alcoxialchil, heterocyclyl, heteroaryl, heteroalkyl, acyl, acyloxy, hydroxyalkyl, amino, acylamino, arylamino, aminoalkyl, aryloxy, the Aral sea is hydroxy, alkoxycarbonyl, alkylamino, alkoxyalkyl, alkylthio, thioalkyl, as well as carboxylic acid or its derivative and a sulfonic acid or its derivative. The substituents defined above.

The group R12can represent hydrogen, linear or branched (C1-C16)alkyl, preferably (C1-C12)alkyl, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, pentyl, hexyl, octyl etc.; hydroxy(C1-C6)alkyl; aryl, such as phenyl, naphthyl, etc.; aralkyl, such as benzyl, phenethyl, etc.; heterocyclyl, such as aziridinyl, pyrrolidinyl, piperidinyl etc.; heteroaryl, such as pyridyl, thienyl, pyrrolyl, furyl, etc.; heteroalkyl, such as furanosyl, pyridylmethyl, oxazolyl, oxazolyl etc.

The ring structure formed by R10together with R12can be pyrrolidin, piperidinyl, morpholinyl, piperazinil etc.

Preferably m is an integer of 0 or 1. When m=0, then Ar preferably denotes unsubstituted or substituted benzofuran, benzoxazole, benzothiazolyl, indolyl, indolinyl, dihydrobenzofuran or dihydrobenzofuranyl, and when m=1, Ar preferably denotes a divalent phenylene, naftilan, pyridyl, chinoline, benzofuran, dihydrobenzofuran, benzopyranyl, dihydrobenzofuranyl, indolyl, indolinyl, isoindolyl, azaindole the Nile, pyrazolyl, benzothiazolyl, benzoxazolyl etc.

When m=0, then Ar preferably denotes a divalent benzofuran and more preferably - benzofuran-2,5-diyl, and when m=1, Ar preferably denotes phenylene. Usually n is an integer from 1 to 4, preferably 1 or 2.

When m=1, then n is preferably equal to 2.

When m=0, n preferably is 1.

Pharmaceutically acceptable salts forming part of the present invention include the salts of such inorganic bases as Li, Na, K, CA, Mg, Fe, Cu, Zn, Mn; salts of such organic bases as N,N'-diacetylethylenediamine, betaine, caffeine, 2-Diethylaminoethanol, 2-dimethylaminoethanol, N-ethylmorpholine, N-ethylpiperidine, glucamine, glucosamine, geranamine (hydrabamine, Isopropylamine, methylglucamine, morpholine, piperazine, piperidine, procaine, purines, theobromine, triethylamine, trimethylamine, Tripropylamine, tromethamine (tromethamine), diethanolamine, meglumine (meglumine, Ethylenediamine, N,N'-diphenylethylenediamine, N,N'-dibenziletilendiaminom, N-benzylpenicillin, choline, choline hydroxide, dicyclohexylamine, benzylamine, phenylethylamine, dialkylamino, trialkylamine, thiamine, aminopyrimidine, aminopyridine, purine, spermidine and so on; such chiral bases, as alkylphenolates, glycinol, phenylglycinol etc; salts of natural amino acids such as glycine, alanine, valine, leucine, isoleucine, norleucine, tyrosine cystine, cysteine, methionine, Proline, hydroxyproline, histidine, ornithine, lysine, arginine, serine, threonine, phenylalanine; unnatural amino acids - D-ISO-Mer and the substituted amino acids; guanidine and substituted guanidine, in which the substituting group may be nitro, amino, alkyl, alkenyl or quinil; ammonium salts or substituted ammonium and aluminium salts. These include salts formed corresponding acid - sulfates, nitrates, phosphates, perchlorates, borates, hydrohalides, acetates, tartratami, maleate, citrates, succinate, palmitate, methane-sulfonates, benzoate, salicylates, hydroxynaphthoate, bansilalpet, ascorbate, glycerophosphate, Ketoglutarate etc. Pharmaceutically acceptable solvate is a hydrate or they may contain other crystallization solvents, for example alcohols.

The most preferred compounds of the present invention include the following:

(E/Z)-3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid, ethyl ester;

(E)-3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid, ethyl ester;

(Z)-3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid, ethyl ester;

(±)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid, methyl ester;

(+)3-[4-[2-(2,3-dihydro-1,4-benzoxa is n-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid, methyl ether;

(-)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid, methyl ester;

(E/Z)-3-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)methylbenzofuran-5-yl]-2-ethoxypropanol acid, ethyl ester;

(E)-3-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)methylbenzofuran-5-yl]-2-ethoxypropanol acid, ethyl ester;

(Z)-3-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)methylbenzofuran-5-yl]-2-ethoxypropanol acid, ethyl ester;

(E/Z)-3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid, ethyl ester;

(E)-3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid, ethyl ester;

(E)-3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid, ethyl ester;

(±)3-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)methylbenzofuran-5-yl]-2-ethoxypropanol acid, methyl ester;

(+)3-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)methylbenzofuran-5-yl]-2-ethoxypropanol acid, methyl ester;

(-)3-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)methylbenzofuran-5-yl]-2-ethoxypropanol acid, methyl ester;

(±)3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid, methyl ester;

(+)3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid, methyl ester;

(-)3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid, milovy ether;

(±)2-methyl-3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid, methyl ester;

(+)- 2-methyl-3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid, methyl ester;

(- )- 2-methyl-3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid, methyl ester;

(±)2-(2-forebesi)-3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid, methyl ester;

(+)2-(2-forebesi)-3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid, methyl ester;

(-)2-(2-forebesi)-3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid, methyl ester;

(E/Z)-3-[4-[2-(3-oxo-2H-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid, ethyl ester;

(E)-3-[4-[2-(3-oxo-2H-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid, ethyl ester;

(E)-3-[4-[2-(3-oxo-2H-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid, ethyl ester;

(±)3-[4-[2-(3-oxo-2H-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid, methyl ester;

(+)3-[4-[2-(3-oxo-2H-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid, methyl ester;

(-)3-[4-[2-(3-oxo-2H-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid, methyl ester;

(E/Z)-3-[6-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]naphthyl]-2-ethoxypropanol the acid, ethyl ether;

(E)-3-[6-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]naphthyl]-2-ethoxypropanol acid, ethyl ester;

(E)-3-[6-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]naphthyl]-2-ethoxypropanol acid, ethyl ester;

(±)3-[6-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]naphthyl]-2-ethoxypropanol acid, methyl ester;

(+)3-[6-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]naphthyl]-2-ethoxypropanol acid, methyl ester;

(-)3-[6-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]naphthyl]-2-ethoxypropanol acid, methyl ester;

(±)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-hydroxypropanoic acid, ethyl ester;

(+)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-hydroxypropanoic acid, ethyl ester;

(-)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-hydroxypropanoic acid, ethyl ester;

(±)3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-hydroxypropanoic acid, ethyl ester;

(+)3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-hydroxypropanoic acid, ethyl ester;

(-)3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-hydroxypropanoic acid, ethyl ester;

(±)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-benzyloxypropionic acid, ethyl ester;

(+)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-benzyloxypropionic acid, ethyl e is Il;

(-)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-benzyloxypropionic acid, ethyl ester;

(±)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-butoxypropan acid, ethyl ester;

(+)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-butoxypropan acid, ethyl ester;

(-)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-butoxypropan acid, ethyl ester;

(±)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-hexyloxyphenol acid, ethyl ester;

(+)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-hexyloxyphenol acid, ethyl ester;

(-)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-hexyloxyphenol acid, ethyl ester;

(±)(E/Z)-3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-phenoxypropanol acid, ethyl ester;

(+)(E)-3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-phenoxypropanol acid, ethyl ester;

(-)(Z)-3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-phenoxypropanol acid, ethyl ester;

(±)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-phenoxypropanol acid, methyl ester;

(+)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-phenoxypropanol acid, methyl ester;

(-)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-phenoxypropanol acid, methyl ester;

(E/Z)-3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-phenoxypropanol acid, ethyl ether;

(E)-3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-phenoxypropanol acid, ethyl ester;

(Z)-3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-phenoxypropanol acid, ethyl ester;

(±)3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-phenoxypropanol acid, methyl ester;

(+)3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-phenoxypropanol acid, methyl ester;

(-)3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-phenoxypropanol acid, methyl ester;

(E/Z)-3-[4-(4-methyl-3,4-dihydro-1,4-benzoxazin-2-yl)methoxyphenyl]-2-ethoxypropanol acid, ethyl ester;

(E)-3-[4-(4-methyl-3,4-dihydro-1,4-benzoxazin-2-yl)methoxyphenyl]-2-ethoxypropanol acid, ethyl ester;

(Z)-3-[4-(4-methyl-3,4-dihydro-1,4-benzoxazin-2-yl)methoxyphenyl]-2-ethoxypropanol acid, ethyl ester;

(±)3-[4-(4-methyl-3,4-dihydro-1,4-benzoxazin-2-yl)methoxyphenyl]-2-ethoxypropanol acid, methyl ester;

(+)3-[4-(4-methyl-3,4-dihydro-1,4-benzoxazin-2-yl)methoxyphenyl]-2-ethoxypropanol acid, methyl ester;

(-)3-[4-(4-methyl-3,4-dihydro-1,4-benzoxazin-2-yl)methoxyphenyl]-2-ethoxypropanol acid, methyl ester;

(E/Z)-3-[4-(4-benzyl-3,4-dihydro-1,4-benzoxazin-2-yl)methoxyphenyl]-2-ethoxypropanol acid, ethyl ester;

(E)-3-[4-(4-benzyl-3,4-dihydro-1,4-benzoxazin-2-yl)methoxyphenyl]-2-etoxy upanova acid, ethyl ether;

(Z)-3-[4-(4-benzyl-3,4-dihydro-1,4-benzoxazin-2-yl)methoxyphenyl]-2-ethoxypropanol acid, ethyl ester;

(±)3-[4-(4-benzyl-3,4-dihydro-1,4-benzoxazin-2-yl)methoxyphenyl]-2-ethoxypropanol acid, methyl ester;

(+)3-[4-(4-benzyl-3,4-dihydro-1,4-benzoxazin-2-yl)methoxyphenyl]-2-ethoxypropanol acid, methyl ester;

(-)3-[4-(4-benzyl-3,4-dihydro-1,4-benzoxazin-2-yl)methoxyphenyl]-2-ethoxypropanol acid, methyl ester;

(±)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid and its salts;

(+)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid and its salts;

(-)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid and its salts;

(±)3-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)methylbenzofuran-5-yl]-2-ethoxypropanol acid and its salts;

(+)3-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)methylbenzofuran-5-yl]-2-ethoxypropanol acid and its salts;

(-)3-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)methylbenzofuran-5-yl]-2-ethoxypropanol acid and its salts;

(±)3-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)methylbenzofuran-5-yl]-2-ethoxypropanol acid and its salts;

(+)3-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)methylbenzofuran-5-yl]-2-ethoxypropanol acid and its salts;

(-)3-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)methylbenzofuran-5-yl]-2-ethoxypropanol acid and its salts;

(±3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid and its salts;

(+)3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid and its salts;

(-)3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid and its salts;

(±)3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-ethoxypropane;

(+)3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-ethoxypropane;

(-)3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-ethoxypropane;

(±)N-methyl-3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-ethoxypropane;

(+)N-methyl-3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-ethoxypropane;

(-)N-methyl-3-[4-[2-(2,3-Dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-ethoxypropane;

(±)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropane;

(+)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropane;

(-)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropane;

(±)N-methyl-3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropane;

(+)N-methyl-3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropane;

(-)N-methyl-3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropane;

(±)N-benzyl-3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropane;

(+)N-benzyl-3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropane;

(-)N-benzyl-3-[4-[2-(2,3-di is Idro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropane;

(±)N-benzyl-3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-ethoxypropane;

(+)N-benzyl-3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-ethoxypropane;

(-)N-benzyl-3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-ethoxypropane;

(±)2-methyl-3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid and its salts;

(+)- 2-methyl-3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid and its salts;

(- )- 2-methyl-3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid and its salts;

(±)2-(2-forebesi)-3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid and its salts;

(+)2-(2-forebesi)-3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid and its salts;

(-)2-(2-forebesi)-3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid and its salts;

(±)3-[4-[2-(3-oxo-2H-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid and its salts;

(+)3-[4-[2-(3-oxo-2H-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid and its salts;

(-)3-[4-[2-(3-oxo-2H-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid and its salts;

(±)3-[4-[2-(3-oxo-2H-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid and its salts;

(+)3-[4-[2-(3-oxo-2H-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid and its salts;

(-)3-[4-[2-(3-oxo-2H-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid and its salts;

(±)3-[6-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]naphthyl]-2-ethoxypropanol acid and its salts;

(+)3-[6-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]naphthyl]-2-ethoxypropanol acid and its salts;

(-)3-[6-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]naphthyl]-2-ethoxypropanol acid and its salts;

(±)3-[6-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]naphthyl]-2-ethoxypropanol acid and its salts;

(+)3-[6-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]naphthyl]-2-ethoxypropanol acid and its salts;

(-)3-[6-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]naphthyl]-2-ethoxypropanol acid and its salts;

(±)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-hydroxypropanoic acid and its salts;

(+)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-hydroxypropanoic acid and its salts;

(-)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-medroxiprogesterona acid and its salts;

(±)3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-hydroxypropanoic acid and its salts;

(+)3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-hydroxypropanoic acid and its salts;

(-)3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-hydroxypropanoic acid and its salts;

(±)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-benzyloxypropionic acid and with whom;

(+)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-benzyloxypropionic acid and its salts;

(-)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-benzyloxypropionic acid and its salts;

(±)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-butoxypropan acid and its salts;

(+)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-butoxypropan acid and its salts;

(-)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-butoxypropan acid and its salts;

(±)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-hexyloxyphenol acid and its salts;

(+)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-hexyloxyphenol acid and its salts;

(-)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-hexyloxyphenol acid and its salts;

(±)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-phenoxypropanol acid and its salts;

(+)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-phenoxypropanol acid and its salts;

(-)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-phenoxypropanol acid and its salts;

(±)3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-phenoxypropanol acid and its salts;

(+)3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-phenoxypropanol acid and its salts;

(-)3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-phenoxypropanol acid and the E. salt;

(±)2-methyl-3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-phenoxypropanol acid, methyl ester;

(+)- 2-methyl-3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-phenoxypropanol acid, methyl ester;

(- )- 2-methyl-3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-phenoxypropanol acid, methyl ester;

(±)2-methyl-3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-phenoxypropanol acid and its salts;

(+)- 2-methyl-3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-phenoxypropanol acid and its salts;

(- )- 2-methyl-3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-phenoxypropanol acid and its salts;

(±)2-methyl-3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-phenoxypropanol acid, methyl ester;

(+)- 2-methyl-3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-phenoxypropanol acid, methyl ester;

(- )- 2-methyl-3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-phenoxypropanol acid, methyl ester;

(±)2-methyl-3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-phenoxypropanol acid and its salts;

(+)- 2-methyl-3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-phenoxypropanol acid and its salts;

(- )- 2-methyl-3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-phenoxypropanol acid and its salts;

(±)3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-etoxy upanova acid, 4-nitrophenyloctyl ether;

(+)3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid, 4-nitrophenyloctyl ether;

(-)3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid, 4-nitrophenyloctyl ether;

(±)3-[4-(4-benzyl-3,4-dihydro-1,4-benzoxazin-2-yl)methoxyphenyl]-2-ethoxypropanol acid and its salts;

(+)3-[4-(4-benzyl-3,4-dihydro-1,4-benzoxazin-2-yl)methoxyphenyl]-2-ethoxypropanol acid and its salts;

(-)3-[4-(4-benzyl-3,4-dihydro-1,4-benzoxazin-2-yl)methoxyphenyl]-2-ethoxypropanol acid and its salts;

(±)3-[4-(4-benzyl-3,4-dihydro-1,4-benzoxazin-2-yl)methoxyphenyl]-2-ethoxypropanol acid, 4-nitrophenyloctyl ether;

(+)3-[4-(4-benzyl-3,4-dihydro-1,4-benzoxazin-2-yl)methoxyphenyl]-2-ethoxypropanol acid, 4-nitrophenyloctyl ether;

(-)3-[4-(4-benzyl-3,4-dihydro-1,4-benzoxazin-2-yl)methoxyphenyl]-2-ethoxypropanol acid, 4-nitrophenyloctyl ether.

In accordance with the present invention, compounds of General formula (I), where R7together with R8form a chemical bond, Y represents an oxygen atom, and R1, R2, R3, R4, R5, R6, R9, R10, X, n, m and Ar are defined previously, can be obtained by any of the pathways described in scheme I.

Scheme I

Path 1. The reaction of compounds of General formula (IIIa)where all symbols identifying the s earlier with the compound of the formula (IIIb), where R9, R10defined earlier excluding hydrogen, and R14means (C1-C6)alkyl, which gives a compound of General formula (I)in which R7together with R8form a chemical bond and Y represents an oxygen atom, can be carried out in the presence of a base such as a hydride of an alkali metal type or NaH KN, organolithium compounds of the type CH3Li, BuLi, alkoxide, such as NaOMe, NaOEt, K+BuO-or mixtures thereof. The reaction may be conducted in the presence of solvents such as THF, dioxane, DMF, DMSO, DME, or mixtures thereof. The solvent can add NMRA as co-solvent. The reaction temperature may range from -78 to 50°C, preferably from -10 to 30°C. the Reaction proceeds more efficiently in anhydrous conditions. The compound of General formula (IIIb) can be obtained by the method described in the literature (Annalen Chemie, (1996) 53, 699).

Alternatively, the compound of formula (I) can be obtained by reaction of compounds of formula (IIIa)where all symbols defined previously, with a Wittig reagent such as Hal-PPh3+CH-(OR9)CO2R10where R9and R10previously defined, by reaction in the same conditions as described above.

Path 2. The reaction of compounds of General formula (IIIc)where all symbols defined previously, the connection is of the General formula (IIId), where R7together with R8form a chemical bond, L1means delete the group, such as halogen atom, n-toluensulfonate, methanesulfonate, trifluromethanesulfonate, preferably a halogen atom, and other symbols defined previously, which gives a compound of General formula (I)defined above may be carried out in the presence of solvents such as DMSO, DMP, DME, THF, dioxane, ether or mixtures thereof. The reaction can be carried out in an inert atmosphere, supporting it with inert gases, such as N2, Ar or Not. The reaction can be carried out in the presence of a base, such as alkali type of NaOH or KOH, carbonate of alkaline metal type sodium carbonate or potassium hydride of an alkali metal type or NaH KN ORGANOMETALLIC base type n-utility, alkali metal amide type sodium amide, or mixtures thereof. The number can be from 1 to 5 equivalents relative to the compound of formula (IIIc), preferably from 1 to 3 equivalents. You can add catalysts phase transfer, such as the tetraalkylammonium halide or hydroxide. The reaction may be conducted at temperatures from 0 to 150°C, preferably from 15 to 100°C. the Duration of the reaction is from 0.25 to 48 hours, preferably from 0.25 to 12 hours.

Path 3. The reaction of the compound of formula (IIIe), where all symbols defined previously, connection with the discharge of formula (IIIf), where R9=R10and both defined earlier excluding hydrogen, which gives a compound of formula (I)in which R7together with R8form a chemical bond, and the remaining symbols are defined earlier may be carried out in the presence of a hydride of an alkali metal type or NaH KN, organolithium compounds of the type CH3Li, BuLi, alkoxide type NaOMe, NaOEt, K+BuO-or mixtures thereof. The reaction can be carried out in the presence of aprotic solvents such as THF, dioxane, DMSO, DMF, DME, or mixtures thereof. The solvent can add NMRA as co-solvent. The reaction temperature may range from -78 to 100°C, preferably from -10 to 50°C.

Path 4. The reaction of compounds of General formula (IIIa)where all symbols previously defined, with a compound of formula (IIIg)where R8means a hydrogen atom, a R9and R10defined earlier may be carried out in the presence of a base. The nature of the base does not matter - you can use any base that is usually used for aldol condensation - metal hydrides type of NaH and Kh, alkoxides of metals of the type NaOMe,+BuO-and NaOEt, amides metals type LiNH2and LiN(iPr)2. You can use the aprotic solvent is THF, ether, dioxane. The reaction can be carried out in an inert atmosphere, supporting it with inert the gas - N2, Ar or Not, and the reaction is more effective in anhydrous conditions. The temperature can be maintained in the range from -80 to 35°C. Receive first β-hydroxypropyl you can degidratiruth under normal conditions of dehydration, such as processing of p-TSA in solvents such as benzene or toluene. The nature of the solvent and dehydrating agent is not of great importance. The temperature can be maintained in the range from 20°C to the boiling point of the solvent, preferably at the boiling temperature of the solvent, with continuous removal of water using nozzles Dean Stark.

Path 5. The reaction of compounds of General formula (IIIh)where all symbols defined previously, a L1means a group to delete a halogen atom, n-toluensulfonate, methanesulfonate, trifluromethanesulfonate, with the compound of formula (IIIi)where R7together with R8form a chemical bond, a R9, R10and Ar is defined previously, which gives a compound of formula (I), where m=1, and the remaining symbols are defined above, can be carried out in the presence of aprotic solvent is THF, DMF, DMSO, DME, or mixtures thereof. The reaction can be carried out in an inert atmosphere, supporting it with inert gases such as Na, Ar or Not. The reaction can be carried out in the presence of base - K2CO3, Na2CO3, NaH or mixtures thereof. The solvent can is about to use acetone, when is Na2CO3or2CO3. The reaction temperature is from 0 to 120°C, preferably from 30 to 100°C. the Duration of the reaction is from 1 to 24 hours, preferably from 2 to 12 hours. The compound of formula (IIIi) can be obtained by the known methods using the reaction of Wittig-Horner between blocked by hydroxyl-arilaldegidov type benzyloxyacetaldehyde and the compound of the formula (IIIb) with the subsequent removal of the protective group.

Path 6. The reaction of compounds of General formula (IIIj)where the notation previously defined, with a compound of General formula (IIIi)where R7together with R8form a chemical bond, and R9, R10and Ar is defined previously, which gives a compound of formula (I), where m=1, and the remaining symbols are defined above, may be carried out using a condensing agent - dicyclohexylamine, triarylphosphine/dialkyldithiocarbamate type PPh3/DEAD and others. The reaction can be carried out in the presence of solvents such as THF, DME, CH2Cl2, CHCl3, toluene, acetonitrile, CCl4and so it is Possible to maintain an inert atmosphere by using inert gases such as N2, Ar or Not. The reaction may be conducted in the presence of DMAP, HOBT, which can be used in the range from 0.05 to 2 equivalents, preferably from 0.25 to 1 equivalent. The reaction temperature is from 0 on the 100° C, preferably from 20 to 80°C. the Duration of the reaction is from 0.5 to 24 hours, preferably from 6 to 12 hours.

In another embodiment of the present invention the compound of General formula (I), where R1, R2, R3, R4, R5, R6, R9, R10, X, n, m and Ar are defined above, R7means a hydrogen atom, hydroxyl, alkoxy, halogen, lower alkyl, unsubstituted or substituted aralkyl, R8means hydrogen, hydroxyl, alkoxy, halogen, lower alkyl, acyl or unsubstituted or substituted aralkyl, a Y signifies oxygen, can be obtained by using one or more processes, presented in scheme II.

Scheme II

Path 7. The recovery of the compounds of formula (IVa), which is a compound of formula (I)in which R7together with R8form a chemical bond, Y represents an oxygen atom, and other symbols defined previously obtained as described previously (scheme I), which gives a compound of General formula (I), where R7and R8represent a hydrogen atom and the other symbols are defined above, can be carried out in the presence of gaseous hydrogen and a catalyst of the type Pd/C, Rh/C, Pt/C. you Can use a mixture of catalysts. The reaction can also be carried out in the presence of solvents such as dioxane, acetic acid, these are the acetate, etc. The pressure can be maintained between atmospheric pressure and 80 psi. You can apply high pressure to reduce the time. The preferred catalyst is 5-10% Pd/C, the number can be from 1 to 50% by weight. The reaction can also be carried out by recovering the metal in a solvent, for example, magnesium in alcohol or sodium amalgam in alcohol, preferably methanol. Hydrogenation may be conducted in the presence of a metal catalyst containing a chiral ligand, receiving compound of formula (I) in optically active form. The metal catalyst may contain rhodium, ruthenium, indium, etc. Chiral ligand is preferably a chiral phosphine, such as (2S,3S)-bis(diphenylphosphino)butane, 1,2-bis(diphenylphosphino)ethane, 1,2-bis(2-methoxyphenylpiperazine)ethane, (-)2,3-isopropylidene-2,3-dihydroxy-1,4-bis(diphenylphosphino)butane, etc. you Can use any chiral catalyst, which gives the desired optical purity of the product (I) (see Principles of Asymmetric Synthesis, Tet. Org. Chem. Series Vol 14, pp.311-316, Ed. Baldwin J.E.).

Path 8. The reaction of the compound of formula (IVb), where R10defined earlier excluding hydrogen, L2means remove the group type of the halogen atom and the other symbols are defined above, with an alcohol of General formula (IVc), where R9defined earlier excluding hydrogen, which gives a compound of formula I, defined above, can be carried out in the presence of solvents such as THF, DMP, DMSO, DME, or mixtures thereof. The reaction can be carried out in an inert atmosphere, supporting it with inert gases - N2, Ar or Not. The reaction may be conducted in the presence of a base is KOH, NaOH, NaOMe, NaOEt, K+BuO-, NaH or mixtures thereof. You can use the catalysts phase transfer, such as the tetraalkylammonium halide or hydroxide. The reaction temperature is from 20 to 120°C, preferably from 30 to 100°C. the Duration of the reaction is from 1 to 12 hours, preferably from 2 to 6 hours. Compounds of General formula (IVb), and receipt of them are disclosed in international publication WO 98/52946.

Path 9. The reaction of the compound of formula (IIIh), defined earlier, with a compound of formula (IIIi)where all symbols are defined above, which gives a compound of formula (I), where m=1, and the remaining symbols are defined above, can be carried out in the presence of solvents such as THF, DMF, DMSO, DME, or mixtures thereof. The reaction can be carried out in an inert atmosphere, supporting it with inert gases, such as N2, Ar or Not. The reaction may be conducted in the presence of a base, such as2CO3, Na2CO3, NaH or mixtures thereof. As a solvent, you can use acetone when the basis is To2CO3or Na2CO3. The reaction temperature is at to 120° C, preferably from 30 to 80°C. the Duration of the reaction is from 1 to 24 hours, preferably from 2 to 12 hours. The compounds of formula (IIIi) can be obtained by reaction of the Wittig-Horner between the locked hydroxyacetaldehyde and the compound of the formula (IIIb), followed by reduction of the double bond and removal of the protective group. On the other hand, the compound of formula (IIIi) can be obtained by the method disclosed in WO 94/01420.

Path 10. The reaction of compounds of General formula (IIIj)defined earlier with a compound of General formula (IIIi)where all symbols defined previously, which gives a compound of formula (I), where m=1, and the remaining symbols are defined above, may be carried out using a condensing agent - dicyclohexylamine, triarylphosphine/dialkyldithiocarbamate type PPh3/DEAD and others. The reaction can be carried out in the presence of solvents such as THF, DME, CH2Cl2, CHCl3, toluene, acetonitrile, CCl4. The reaction can be carried out in an inert atmosphere, supporting it with inert gases, such as N2, Ar or Not. The reaction may be conducted in the presence of DMAP, NOWT that can be used in the range from 0.05 to 2 equivalents, preferably from 0.25 to 1 equivalent. The reaction temperature is 0 to 100°C, preferably from 20 to 80°C. the Duration of the reaction is from 0.5 to 24 hours, preferably from 6 is about 12 hours.

Path 11. The reaction of the compound of formula (IVd), which is a compound of formula (I), where R9means a hydrogen atom, and other symbols previously defined, with a compound of formula (IVe), where R9defined earlier excluding hydrogen, a L2means the group that you want the type of halogen atom, can be carried out in the presence of solvents such as THF, DME, DMSO, DME and other Reaction can be carried out in an inert atmosphere, supporting it with inert gases, such as N2, Ar or Not. The reaction can be carried out in the presence of a base, such as KOH, NaOH, NaOMe, K+BuO-, NaH, etc. Can be applied catalysts phase transfer, such as halide of or tetraalkylammonium hydroxide. The reaction temperature is from 20 to 150°C, preferably from 30 to 100°C. the Duration of the reaction is from 1 to 12 hours, preferably from 2 to 6 hours.

The path 12. The reaction of compounds of General formula (IIIa)as defined above, with a compound of formula (IIIg)where R8means hydrogen, a R9and R10defined earlier may be carried out under normal conditions. The nature of the base does not matter - you can use any base that is usually used for aldol condensation - metal hydrides type of NaH and Kh, alkoxides of metals of the type NaOMe,+BuO-and NaOEt, amides metals type LiNH2and LiN(iPr)2. It is possible when Enate aprotic solvent as THF. You can use an inert atmosphere type argon. The reaction is more effective in anhydrous conditions. The temperature can be maintained in the range from -80°to 25°C. β-Hydroxyindole product can be dehydrosilybin conventional methods, for example by the method of ionic hydrogenation by treating trialkylsilanes in the presence of acid such as triperoxonane. You can use a solvent such as CH2Cl2. The reaction preferably proceeds at 25°C. you Can use a higher temperature, if the reaction proceeds slowly.

The path 13. The reaction of compounds of General formula (IIIc), where the notation previously defined, with a compound of General formula (IIId), where L1means delete the group, such as halogen atom, p-toluensulfonate, methanesulfonate, triftorbyenzola, preferably a halogen atom, and other symbols are defined above, which gives a compound of General formula (I)may be carried out in the presence of solvents such as DMSO, DMF, DME, THF, dioxane, ether or mixtures thereof. The reaction can be carried out in an inert atmosphere, supporting it with inert gases, such as N2, Ar or Not. The reaction can be carried out in the presence of a base, such as alkali type of NaOH, KOH, carbonate of alkaline metal type sodium carbonate or potassium, alkali metal hydride type of NaH ilicn, ORGANOMETALLIC base type n-utility, alkali metal amide type sodium amide, or mixtures thereof. The number can be from 1 to 5 equivalents relative to the compound of formula (IIIc), preferably from 1 to 3 equivalents. The reaction may be conducted at temperatures from 0 to 150°C, preferably from 15°to 100°C. the Duration of the reaction is from 0.25 to 24 hours, preferably from 0.25 to 12 hours.

The path 14. The transformation of compounds of formula (IVf), where all symbols defined previously, in the compound of formula (I)where all symbols are defined earlier may be carried out in the presence of either base or acid, and the choice of base or acid is not essential. You can use any base that is usually used for the hydrolysis of the nitrile to the acid, such as a hydroxide of the metal type of NaOH or KOH in an aqueous solvent, any acid which is generally used in the hydrolysis of the nitrile to the ether, such as anhydrous HCl in that alcohol, like methanol, ethanol, propanol, etc. the Reaction can be conducted at temperatures ranging from 25°C to the boiling point of the solvent. The duration of reaction is from 0.25 to 48 hours.

Path 15. The reaction of the compound of formula (IVg), where R10defined earlier excluding hydrogen and all other symbols are defined above, with a compound of formula (IVc), where R defined earlier excluding hydrogen, which gives a compound of formula (I) (reaction joining catalyzed by carbenoid rhodium), can be carried out in the presence of salts of rhodium (II), for example, acetate, rhodium (II). The reaction can be carried out in the presence of solvents such as benzene, toluene, dioxane, ether, THF or mixtures thereof, or, where possible, in the presence of a solvent R9HE, at any temperature providing a sufficient rate of formation of product, usually at a high temperature, for example, the boiling temperature of the solvent. It is possible to maintain an inert atmosphere by using inert gases such as N2, Ar or Not. The duration of the reaction is from 0.5 to 24 hours, preferably from 0.5 to 6 hours.

The compound of formula (I), where R1means a hydrogen atom, can be obtained by hydrolysis, by standard methods, the compounds of formula (I), where R10means all groups defined earlier excluding hydrogen. The hydrolysis can be carried out in the presence of such grounds, as Na2CO3and the corresponding solvent-type methanol, ethanol or mixtures thereof. The reaction may be conducted at a temperature of from 20 to 40°C, preferably from 25 to 30°C. the Duration of the reaction is from 2 to 12 hours, preferably from 4 to 8 hours.

The compound of General formula (I)where Y represents oxygen and R10Osnach is no hydrogen or lower alkyl, can be converted into a compound of formula (I)where Y represents NR12by reaction with an appropriate amine of the formula with other10R12where R10and R12previously defined, which gives the compound of formula (I)where Y represents NR12and the remaining symbols are defined above. Alternatively, the compound of formula (I), where YR10means HE can turn into gelegenheid, preferably YR10=Cl, by reaction with an appropriate reagent - oxalylamino, minikleid etc., followed by treatment of the amine of the formula with other10R12where R10and R12previously defined. Alternatively, from the compounds of formula (I), where YR1means HE and the rest of the notation defined previously, you can get a mixed anhydride by treatment with galogenangidridy, such as acetylchloride, acetylmuramic, pivaloyloxy, dichlorobenzophenone and other Reaction can be carried out in the presence of an appropriate base, such as pyridine, triethylamine, diisopropylethylamine, etc. Can be used solvents such as halogenated hydrocarbon type CHCl3or CH2Cl2, hydrocarbons, such as benzene, toluene, xylene and other Reaction can be conducted at temperatures from -40 to 40°C, preferably from 0 to 20°C. thus Obtained gelegenheid or mixed anhydride can ZAT is m to process the corresponding amine of the formula with other 10R12where R10and R12defined previously, obtaining the compound of formula (I)where Y represents NR12and the remaining symbols are defined above.

The method of obtaining compounds of formula (IIIa) described in international publication WO 98/52946.

In another embodiment of the present invention provides a new intermediate compound of formula (IVf):

where the group R1, R2, R3, R4group and R5and R6when they are connected with the carbon atom may be identical or different, representing hydrogen, halogen, hydroxyl, nitro, piano, formyl or unsubstituted or substituted groups as alkyl, cycloalkyl, alkoxy, cycloalkene, aryl, aryloxy, aralkyl, Alcoxy, heterocyclyl, heteroaryl, heteroalkyl, heteroaromatic, heteroaromatic, acyl, acyloxy, amino, acylamino, monoalkylamines, dialkylamines, arylamino, aralkylamines, alkoxycarbonyl, aryloxyalkyl, arelaxation, alkylthio, alkoxycarbonyl, aryloxides-Beniamino, alcoxycarbenium, as well as carboxylic acid or its derivatives or sulfonic acid or its derivatives; R5and R6one, or both, can also be oxoprop when they are linked to the carbon atom; when R5and R6linked to the nitrogen atom, they represent the Oh hydrogen, hydroxyl, formyl or unsubstituted or substituted groups as alkyl, cycloalkyl, alkoxy, cycloalkene, aryl, aralkyl, heterocyclyl, heteroaryl, heteroalkyl, acyl, acyloxy, amino, acylamino, monoalkylamines, dialkylamines, arylamino, aralkylamines, aryloxy, Alcoxy, heteroaromatic, heteroaromatic, alkoxycarbonyl, aryloxyalkyl, arelaxation, alkylthio, as well as derivatives of carboxylic acids or derivatives of sulfonic acids; x is the heteroatom selected from oxygen, sulfur or NR11where R11means hydrogen or a unsubstituted or substituted group as alkyl, cycloalkyl, aryl, aralkyl, acyl, alkoxycarbonyl, aryloxyalkyl or arelaxation; Ar denotes unsubstituted or substituted divalent unfused or condensed, aromatic or heterocyclic group; R7means a hydrogen atom, hydroxyl, alkoxy, halogen, lower alkyl, unsubstituted or substituted aralkyl, or forms a bond with a neighboring group, R8; R8means hydrogen, hydroxyl, alkoxy, halogen, lower alkyl, acyl, unsubstituted or substituted aralkyl, or forms a bond with a neighboring group, R7; R9means hydrogen or a unsubstituted or substituted group as alkyl, cycloalkyl, aryl, aralkyl, alkoxycarbonyl, aryloxyalkyl, Alki aminocarbonyl, allumination, acyl, heterocyclyl, heteroaryl or heteroalkyl; port group -(CH2)n-(O)m- can join via the nitrogen atom or via a carbon atom; n is an integer from 1 to 4, a m is the integer 0 or 1, and a method of its production and use in preparation of β-aryl-α-oxiclean alkylcarboxylic acids.

The compounds of formula (IVf), where R7and R8mean hydrogen atoms, and the remaining notation defined earlier, get, shown in Scheme III.

Scheme III

The reaction of the compound of formula (IIIa)where all symbols previously defined, with a compound of formula (IVh), where R9defined earlier excluding hydrogen, a Hal means a halogen atom such as Cl, Br or I, which gives the compound of formula (IVi), may be conducted under normal conditions in the presence of a base. The nature of the base does not matter - you can use any base commonly used in the Wittig reaction, such as metal hydrides type or NaH KN, alkoxides of metals of the type NaOMe, K+BuO-or NaOEt, amides metals type LiNH2or LiN(iPr)2. You can apply aprotic solvents such as THF, DMSO, dioxane, DME, or a mixture of solvents. The solvent can add NMRA as co-solvent. You can use inert the th atmosphere, supporting her with inert gases such as argon. The reaction proceeds more efficiently in anhydrous conditions. The temperature can be maintained in the range from -80 to 100°C.

Connection (IVi), where all symbols defined previously and R9defined earlier excluding hydrogen, can be converted into a compound of formula (IVj), where R7and R8mean hydrogen atoms, and the remaining notation defined previously, by treating it with an alcohol of formula R9OH, where R9defined earlier excluding hydrogen, anhydrous conditions in the presence of a strong anhydrous acid type n-toluensulfonate acid. When processing the compounds of formula (IVj), as defined above, trialkylsilanes type trimethylsilylacetamide produces compound of formula (IVf), where R7and R8mean atoms podroda, R9defined earlier excluding hydrogen and all other symbols are defined above.

In the next version of the embodiment of the present invention provides a new intermediate compound of formula (IVg):

where the group R1, R2, R3, R4group and R5and R6when they are connected with the carbon atom may be identical or different, representing hydrogen, halogen, hydroxyl, nitro, cyano, formyl or unsubstituted or substituted groups as alkyl, t is cloaker, alkoxy, cycloalkene, aryl, aryloxy, aralkyl, Alcoxy, heterocyclyl, heteroaryl, heteroalkyl, heteroaromatic, heteroaromatic, acyl, acyloxy, amino, acylamino, monoalkylamines, dialkylamines, arylamino, aralkylamines, alkoxycarbonyl, aryloxyalkyl, arelaxation, alkylthio, alkoxycarbonyl, aryloxypropanolamine, alcoxycarbenium, as well as carboxylic acid or its derivatives, or sulfonic acid or its derivatives; R5and R6one or both may also be oxoprop when they are linked to the carbon atom; when R5and R6linked to the nitrogen atom, they represent a hydrogen, hydroxyl, formyl or unsubstituted or substituted groups as alkyl, cycloalkyl, alkoxy, cycloalkene, aryl, aralkyl, heterocyclyl, heteroaryl, heteroalkyl, acyl, acyloxy, amino, acylamino, monoalkylamines, dialkylamines, arylamino, aralkylamines, aryloxy, Alcoxy, heteroaromatic, heteroaromatic, alkoxycarbonyl, aryloxyalkyl, arelaxation, alkylthio, as well as derivatives of carboxylic acids or derivatives of sulfonic acids; x is the heteroatom selected from oxygen, sulfur or NR11where R11means hydrogen or a unsubstituted or substituted group as alkyl, cycloalkyl, aryl, aralkyl, acyl, alkoxycarbonyl, arelaxation the l or arelaxation; Ar denotes unsubstituted or substituted divalent unfused or condensed, aromatic or heterocyclic group; R7means a hydrogen atom, hydroxyl, alkoxy, halogen, lower alkyl, unsubstituted or substituted aralkyl; R10means hydrogen or a unsubstituted or substituted group as alkyl, cycloalkyl, aryl, aralkyl, heterocyclyl, heteroaryl or heteroalkyl; port group -(CH2)n-(O)m- can join via the nitrogen atom or via a carbon atom; n is an integer from 1 to 4, m is an integer of 0 or 1, and the method of its production and use in preparation of β-aryl-α-oxiclean alkylcarboxylic acids.

The compound of formula (IVg), where the notation previously defined, can be obtained by reaction of compounds of formula (IVk):

where R8means a hydrogen atom, and other symbols previously defined, with an appropriate diazotizing agent.

The reaction diazotizable is carried out under standard conditions. Preferably diazotizing agent is alkynylaryl, for example, isoamylase. The reaction can be carried out in the presence of solvents such as THF, dioxane, ether, benzene, or mixtures thereof. Temperature range from -50 to 80°C. the Reaction can be carried out in an inert atmosphere, the support is of IVA it with inert gases, such as the N2, Ar or Not. The duration of the reaction is from 1 to 24 hours, preferably from 1 to 12 hours.

The compound of formula (IVk) can be obtained by reaction between (IIIh)where the notation previously defined, with a compound of formula (IVl):

where R8means a hydrogen atom and the other symbols are defined above.

The reaction of the compound of formula (IIIh)where the notation previously defined, with a compound of formula (IVl), where all symbols are defined earlier may be carried out in the presence of solvents such as THF, DMF, DMSO, DME, or mixtures thereof. The reaction can be carried out in an inert atmosphere, supporting it with inert gases, such as N2, Ar or Not. The reaction can be carried out in the presence of such grounds as2CO3, Na2CO3or NaH or mixtures thereof. As a solvent, you can use acetone when is Na2CO3or2CO3. The reaction temperature is from 20 to 120°C, preferably from 30 to 80°C. the Duration of the reaction is from 1 to 24 hours, preferably from 2 to 12 hours.

In this application the expression "pure" means that the reaction is carried out without using solvent.

It is understood that in any of the above reactions, any reactive group in the substrate molecule may be protective is placed in accordance with standard chemical practice. Protective groups in all of these reactions are preferably those groups that are usually used in this field. Methods of formation and removal of such protective groups - standard, their choice is determined by the type of secure connection and the protective group.

Pharmaceutically acceptable salts are obtained by reaction of compounds of formula (I) with 1-4 equivalents of base, such as NaOH, sodium methoxide, sodium hydride, CON, m-butoxide potassium, calcium hydroxide, magnesium and others, in solvents such as ether, THF, methanol, m-butanol, dioxane, isopropanol, ethanol, etc. Can be used solvent mixtures. It is also possible to use organic bases such as lysine, arginine, diethanolamine, choline, guanidine and derivatives thereof. On the other hand, when applicable, receive the salt of the corresponding acid in the processing of such acids as hydrochloric, HBr, nitric, sulfuric, phosphoric, n-toluensulfonate, methanesulfonate, acetic, maleic, salicylic, hydroxynaphthalene, ascorbic, palmitic, succinic, benzoic, benzolsulfonat, tartaric acid and others, in solvents such as ethyl acetate, ether, alcohols, acetone, THF, dioxane, etc. you Can use a mixture of solvents.

The stereoisomers of the compounds included in the composition of the present invention can be obtained by using reagents that have only one enantion the RNA form, if this is possible, or by conducting the reaction in the presence of reagents or catalysts having only one enantiomeric form, or by separating a mixture of stereoisomers, standartnimi methods. To preferred methods include microbiological separation, separation of the diastereomeric salts formed with chiral acids - almond, camphorsulfonate, tartaric, lactic and other acids, if applicable, or salts of chiral bases such as brucine, alkaloids, Cinchona, their derivatives and other Common methods presented in the collection of Jaques et al. "Enantiomers, Racemates and Resolution" (Wiley Interscience, 1981). In particular, the compound of formula (I), where YR10HE is a, can be transformed into a mixture of diastereomeric amides (1:1) by treatment with chiral amines, aminoacids, aminoalcohols derived amino acids; acid can be turned into alcohol in a standard reaction conditions; diastereoisomer can be divided by fractional crystallization or chromatography; and stereoisomers of the compounds of formula (I) can be obtained by hydrolysis of purified diastereomeric amide.

Different polymorphic forms of the compounds of General formula (I), the components of the present invention, can be obtained by crystallization of the compounds of formula (I) in various conditions. for example, applying for recrystallization, the difference is these types of solvents, carrying out the crystallization at different temperatures by applying during the crystallization of the various modes of cooling, ranging from very fast to very slow. Polymorphic forms can also be obtained by heating or melting compounds with subsequent gradual or fast cooling. The presence of polymorphic forms can be determined using NMR spectroscopy of solid samples, IR spectroscopy, differential scanning calorimetry, x-ray diraction processes in powder and other methods.

The present invention provides a pharmaceutical composition comprising compounds of General formula (I)defined above, their derivatives, analogs, tautomeric forms, stereoisomers, polymorphic forms, pharmaceutically acceptable salt or pharmaceutically acceptable solvate together with conventional pharmaceutical excipients, diluents, etc. that can be used for the treatment and/or prevention of diseases such as hypertension, ischemic heart disease, atherosclerosis, stroke, peripheral vascular disease and related diseases. These compounds can also be used for treatment of familial hypercholesterolemia, hypertriglyceridemia, to reduce atherogenic lipoproteins lonp and LDL. Compounds of the present invention can be used to treat some kidney the disease, including glomerulonephritis, glomerulosclerosis, nephrotic syndrome, hypertensive nephrosclerosis, nephropathy. Compounds of General formula (I) can also be useful in the treatment/prevention of resistance to insulin (type II diabetes), resistance to leptin, disorders of glucose tolerance, dyslipidemia, disorders related to syndrome X such as hypertension, obesity, insulin resistance, coronary heart disease and other cardiovascular diseases. These compounds can also be useful as inhibitors alsoreported to improve mental abilities in dementia, as inflammatory means, in the treatment of diabetic complications, diseases associated with activation of endothelial cells, psoriasis, polycystic ovarian syndrome (PCOS), inflammatory colitis, osteoporosis, motonishi dystrophy, pancreatitis, retinopathy, arteriosclerosis, xanthoma and in the treatment of cancer. Compounds of the present invention can be used in the treatment and/or prophylaxis of the aforementioned diseases in combination/ simultaneously with one or more inhibitors of HMG:COA-reductase and such hypolipidemic/hypolipoproteinemia means, such as derivatives fibre acid, nicotinic acid, cholestyramine, colestipol, probucol and combinations thereof. Compounds of the present and the gain can be introduced in combination with inhibitors of HMG:COA-reductase and lipid/hypolipoproteinemia means together or during treatment so that so they acted synergistically. Inhibitors of HMG:COA-reductase choose from among those that are used for treatment or prophylaxis of hyperlipidemia, such as lovastatin, pravastatin, simvastatin, fluvastatin, atorvastatin, tseriwastatina and their analogues. Derived fibre acid is preferably used gemfibrozil, clofibrate, fenofibrate, ciprofibrate, bezafibrate and their equivalents.

The present invention also provides a pharmaceutical composition comprising compounds of General formula (I)defined above, their derivatives, analogs, tautomeric forms, stereoisomers, polymorphic forms, pharmaceutically acceptable salt or pharmaceutically acceptable solvate with one or more inhibitors of HMG:COA-reductase and such hypolipidemic/hypolipoproteinemia means, such as derivatives fibre acid, nicotinic acid, cholestyramine, colestipol, probucol in combination with conventional pharmaceutical excipients, diluents, etc.

The pharmaceutical composition can be used in conventional dosage forms - tablets, capsules, powders, syrups, solutions, suspensions, etc., it may contain flavors, sweet substances, etc. in the appropriate solid or liquid fillers or diluents, or in suitable sterile media to form Rast is ora or suspension for injection. Such compositions typically contain from 1 to 20%, preferably from 1 to 10% of active compound by weight, the rest is pharmaceutically acceptable excipients, diluents or solvents.

Pharmaceutically acceptable excipients are preferably solid fillers or diluents and sterile aqueous or organic solutions. In these pharmaceutical compositions the active ingredient is in an amount sufficient to provide the desired dosage in the range described above. So, for internal use polymorphic form can be combined with an appropriate solid or liquid filler, receiving capsules, tablets, powders, syrups, solutions, suspensions, etc. If necessary, the pharmaceutical composition may contain additional components, flavors, sweet substances, excipients, etc. For parenteral administration polymorphic form can be combined with sterile aqueous or organic media, getting a solution or suspension for injection. For example, you can use the solutions in sesame or peanut oil, aqueous propylene glycol, etc. and aqueous solutions of water-soluble, pharmaceutically acceptable salts of the corresponding acids or bases formed by these compounds. In solutions for injection active ingredient can be the ü dissolved in polyhydroxyalkane castor oil. Solutions for injection, thus obtained, can then be administered intravenously, intraperitoneally, subcutaneously or intramuscularly, and intramuscular injection preferably in humans.

For insertion through the nose, the preparation may contain polymorphic forms of the present invention dissolved or suspended in a liquid filler, preferably water, for use in aerosol form. The filler may contain such additives as soljubilizatory type of propylene glycol, surfactants, amplifiers suction - lecithin (phosphatidylcholine) or cyclodextrin, or preservatives like parabens.

Tablets, coated tablets or capsules containing talc and/or binder based on carbohydrates, especially preferred for internal use. The excipients for tablets, coated tablets and capsules are preferably lactose, corn starch and/or potato starch. You can use syrup or elixir in cases where you can use sweetened media.

A typical method of manufacture of tablets revealed by the following example.

Examples of preparation tablets

A) 1) Active ingredient30 g
2) Lactose95 g
3) corn Starch30 g
4) Carboxymethylcellulose44 g
5) magnesium Stearate1 g
200 g per 1000 tablets

Prepare a homogeneous mixture of ingredients 1-3 with water and granularit after drying under reduced pressure. The granules are thoroughly mixed with ingredients 4 and 5 and are compressed in a tablet press machine, receiving 1000 tablets containing 30 mg of active ingredient.

B) 1) Active ingredient30 g
2) calcium Phosphate90 g
3) Lactose40 g
4) corn Starch35 g
5) Polyvinylpyrrolidone3.5 g
6) magnesium Stearate1.5 g
200 g per 1000 tablets

Prepare a homogeneous mixture of ingredients 1-4 with an aqueous solution of ingredient 5 and granularit after drying under reduced pressure. Add ingredient 6 and granules are compressed in a tablet press machine, receiving 1000 tablets containing 30 mg of ingredient 1.

The compounds of formula (I)defined above, in clinical practice, introduced mammals, including humans, through the mouth, nose, lungs, through the skin, or parenteral, rectal is but in the form of a depot, subcutaneous, intravenous, intramuscular, intraurethral, intranasal, in the form of an ophthalmic solution or ointment. The preferred method of administration is oral (ingestion), as a more convenient and does not cause pain and irritation, as by injection. However, when the patient is unable to swallow the medicine, or when violations drug intake due to illness or other anomalies, the drug must enter the parenteral. Any method of administration the dosage is from 0.01 to 100 mg/kg of body weight per day, preferably from 0.01 to 30 mg/kg of body weight per day, in one or several stages. However, for optimal patient dosage defines the person responsible for treatment, and usually give a smaller dose and then gradually increase to establish the best dosage.

Information confirming the possibility of carrying out the invention

Hereinafter the invention is explained in detail in the examples which are given for illustration only, but not intended to limit the scope of the invention.

INTERMEDIATE SYNTHESIS of 1

(±)4-[2-(3-Oxo-2H-1,4-benzoxazin-4-yl)ethoxy]benzaldehyde

A mixture of 2H-1,4-benzoxazin-3-(4H)-she (1.6 g, is 10.7 mmol), 4-(2-bromoethoxy)benzaldehyde (2,95 g, 12.8 mmol) and potassium carbonate (5,93 g, 42,97 mmol) in anhydrous who dimethylformamide (30 ml) was stirred at 80° C for 10 hours. Was added water (100 ml) and was extracted with ethyl acetate (2×75 ml). The organic layers were combined, washed with water (50 ml) and saturated NaCl solution (50 ml), dried (Na2SO4), filtered and the solvent evaporated. The residue was subjected to chromatography on silica gel using a mixture of ethyl acetate and petroleum ether (2:8), receiving specified in the title compound (2.9 g, 91%) as colorless solids with TPL 75-78°C.

1H-NMR (CDCl3, 200 MHz): δ 4,37 (s, 4H), to 4.62 (s, 2H), of 6.96-7,26 (complex, 6N), of 7.82 (d, J=8,40 Hz, 2H), of 9.89 (s, 1H).

INTERMEDIATE SYNTHESIS of 2

(±)6-[2-(2,3-Dihydro-1,4-benzothiazin-4-yl)ethoxy]cyanonaphthalene

A mixture of 2-(2,3)-dihydro-1,4-benzothiazin-4-yl)ethylmethanesulfonate (0,49 g, 1.82 mmol), 2-hydroxy-6-cyanonaphthalene (0.28 g, of 1.65 mmol) and potassium carbonate (1,15 g of 8.28 mmol) in anhydrous dimethylformamide (30 ml) was stirred at 80°C for 12 hours. Was added water (50 ml) and was extracted with ethyl acetate (2×25 ml). Layers of ethyl acetate were combined, washed with water (25 ml) and saturated NaCl (20 ml), dried (Na2SO4), filtered and the solvent evaporated under reduced pressure. The residue was subjected to chromatography on silica gel using a mixture of ethyl acetate and petroleum ether (2:8), receiving specified in the header connection (0,41 g, 72%) as the ledno-yellow solid with TPL 94-96°C.

1H-NMR (CDCl3, 200 MHz): δ 3,05 (t, J=to 5.21 Hz, 2H), 3,79-3,85 (complex, 4H), or 4.31 (t, J=of 5.82 Hz, 2H), 6,64-6,78 (complex, 2H), 6,97-of 7.25 (complex, 4H), 7,53-7,80 (complex, 3H), 8,13 (s, 1H).

INTERMEDIATE SYNTHESIS of 3

(±)6-[2-(2,3-Dihydro-1,4-benzothiazin-4-yl)ethoxy]naphthaldehyde

(±)6-[2-(2,3-Dihydro-1,4-benzothiazin-4-yl)ethoxy]cyanonaphthalene (8 g, with 22.9 mmol)obtained in the intermediate synthesis of 2, was dissolved in anhydrous tetrahydrofuran (15 ml) and the resulting solution was slowly added diisobutylaluminum (93 ml, 20% in toluene) at -70°C for 1 hour. After complete addition the reaction mixture was stirred at 25°C for 16 hours. At the end was added ethyl formate (20 ml) and stirred at 25°C for 1 hour. Was added a saturated solution of ammonium chloride (15 ml). The mixture was acidified with 10% sulfuric acid and was extracted with ethyl acetate (2×75 ml). Layers of ethyl acetate were combined, washed with water (2×50 ml) and saturated NaCl solution (50 ml), dried (Na2SO4), filtered and the solvent evaporated under reduced pressure. The residue was subjected to chromatography on silica gel using a mixture of ethyl acetate and petroleum ether (10:90), getting mentioned in the title compound (4.5 g, 56%) as a pale yellow solid with TPL 100-102°C.

1H-NMR (CDCl3 , 200 MHz): δ a 3.06 (t, J=5,20 Hz, 2H), 3.72 points-3,86 (complex, 4H), to 4.33 (t, J=5,67 Hz, 2H), 6,60-6,79 (complex, 2H), 6,97-of 7.25 (complex, 4H), 7,74-7,93 (complex, 3H), of 8.25 (s, 1H), to 10.09 (s, 1H).

INTERMEDIATE SYNTHESIS of 4

(±)4-[4-Methyl-3,4-dihydro-1,4-benzoxazin-2-yl]methoxybenzaldehyde

4-Methyl-3,4-dihydro-1,4-benzoxazin-2-methanol (6.0 g, a 33.5 mmol) was dissolved in dichloromethane (20 ml) and the resulting solution was added triethylamine (10,15 g, 100,5 mmol) under nitrogen atmosphere at 25°C. To this reaction mixture was added methanesulfonamide (5.75 g, 50,25 mmol) at 0°and was stirred at 25°C for 10 hours. Was added water (50 ml) and was extracted with chloroform (2×25 ml). The organic extracts were combined, washed with water (50 ml), dried (Na2SO4), filtered and the solvent evaporated under reduced pressure. The residue was subjected to chromatography on silica gel using a mixture of ethyl acetate and hexane (2:8)to give (4-methyl-3,4-dihydro-2H-1,4-benzoxazin-2-yl)methylmethanesulfonate (3.7 g, 43%) as syrup.

1H-NMR (CDCl3, 200 MHz): δ is 2.88 (s, 3H), of 3.07 (s, 3H), 3,13-3,31 (complex, 2H), to 4.41 (d, J=5,20 Hz, 2H), 4.53-in-4,55 (complex, 1H), for 6.81-6.89 in (complex, 4H).

A mixture of (4-methyl-3,4-dihydro-1,4-benzoxazin-2-yl)methylmethanesulfonate (3.7 g, 14,39 mmol), 4-hydroxybenzaldehyde (2.6 g, 21,29 mmol) and potassium carbonate (5.9 g, and 42.7 mmol) in anhydrous dimethylformamide (30 ml) per Merivale at 80° C for 10 hours. Was added water (100 ml) and was extracted with ethyl acetate (2×70 ml). The organic layers were combined, washed with water (50 ml) and saturated NaCl solution (50 ml), dried (Na2SO4), filtered and the solvent evaporated under reduced pressure. The residue was subjected to chromatography on silica gel using a mixture of ethyl acetate and petroleum ether (2:8), receiving specified in the title compound (1.3 g, 32%) as a thick liquid.

1H-NMR (CDCl3, 200 MHz): δ of 2.93 (s, 3H), 3,24-of 3.46 (complex, 2H), 4,14-4,37 (complex, 2H), 4,68-4,71 (complex, 1H), 6,72-7,10 (complex, 6N), 7,86 (d, J=8,80 Hz, 2H), 9,92 (s, 1H).

INTERMEDIATE SYNTHESIS of 5

(±)4-[4-Benzyl-3,4-dihydro-1,4-benzoxazin-2-yl]methoxybenzaldehyde

The specified connection (3.2 g, 80%) was obtained as a pale yellow solid from 4-benzyl-3,4-dihydro-1,4-benzoxazin-2-methanol (4.0 g, 15,68 mmol) using the procedure similar to that described in intermediate synthesis 4. TPL 92-94°C.

1H-NMR (CDCl3, 200 MHz): δ 3,38-3,43 (complex, 2H), 4,14-4,32 (complex, 2H), 4,46 (d, J=7,80 Hz, 2H), 4,60 with 4.65 (complex, 1H), 6,65-6,89 (complex, 4H), 7,00 (d, J=8,80 Hz, 2H), 7,32 (s, 5H), 7,83 (d, J=8,80 Hz, 2H), 9,90 (s, 1H).

EXAMPLE 1

(E/Z)-3-[4-[2-(2,3-Dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid, ethyl ester

Cooled in ice, the suspension is of Idrija sodium (60% suspension in oil) (1.39 g, of 29.1 mmol) in anhydrous tetrahydrofuran (5 ml) with stirring under nitrogen atmosphere was slowly added a solution of triethyl-2-ethoxypropionate (W.Grell and H. Machleidt, Annalen Chemie, 1960, 699, 53) (7,8 g of 29.1 mmol) in anhydrous tetrahydrofuran (15 ml). The mixture was stirred for 30 minutes at 0°and then the solution was added 4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]benzaldehyde (7.5 g, about 26.5 mmol)obtained by the method described in intermediate synthesis of 1 and described in international publication WO 98/52946, in anhydrous tetrahydrofuran (20 ml). The mixture was heated to 25°C and stirred for another 20 hours. The solvent is evaporated and the dry residue suspended in water (100 ml) and was extracted with ethyl acetate (2×75 ml). Layers of ethyl acetate were combined, washed with water (75 ml) and saturated NaCl solution (50 ml), dried (Na2SO4), filtered and the solvent evaporated under reduced pressure. The residue was subjected to chromatography on silica gel using a mixture of ethyl acetate and petroleum ether (2:8) as eluent, obtaining mentioned in the title compound (8.0 g, 75%) as a resin (a mixture of geometrical isomers (E/Z in the ratio 65:35) (R.A.Aitken and G.L.Thom, Synthesis, 1989, 958).

1H-NMR (CDCl3, 200 MHz): δ of 1.18 and 1.36 (United, 6N, isomeric OEt, triplet signals), 3,51 (t, J=4,48 Hz, 2H), 3,71 (t, J=5,39 Hz, 2H), 3,89-a 4.03 (complex, 2H), 4,10-4,34 (complex, 6N), 6,07 (s, 0,35H, olefinic proton isomer is), 6,63-7,14 (complex, 6,N), 7,73 (d, J=8,72 Hz, 2H).

EXAMPLE 2

(±)3-[4-[2-(2,3-Dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid, methyl ester

A mixture of ethyl ester of (E/Z)-3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]-phenyl]-2-ethoxypropanol acid (8.0 g, 20.0 mmol)obtained in example 1 and magnesium shavings (for 9.64 g, 396,7 mmol) in anhydrous methanol (50 ml) was stirred at 25°C for 20 hours. After this was added water (50 ml), brought to approximately pH 7.0 using 10% aqueous hydrochloric acid and the solution was extracted with ethyl acetate (2×10 ml). The organic extracts were combined, washed with water (75 ml) and saturated NaCl solution (75 ml), dried (Na2SO4), filtered and solvent was removed under reduced pressure. The residue was subjected to chromatography on silica gel using a mixture of ethyl acetate and petroleum ether (2:8) as eluent, obtaining mentioned in the title compound (5.0 g, 64%) as a resinous liquid.

1H-NMR (CDCl3, 200 MHz): δ to 1.15 (t, J=7,00 Hz, 3H), of 2.93 (d, J=6,64 Hz, 2H), 3,23-3,38 (complex, 1H), 3,43-3,72 (complex, 8H), of 3.97 (t, J=6,90 Hz, 1H), 4,14 (t, J=of 5.81 Hz, 2H), 4,19 (t, J=4,20 Hz, 2H), 6,55-6,83 (complex, 6N), 7,13 (d, J=8,39 Hz, 2H).

EXAMPLE 3

(E/Z)-3-[2-(2,3-Dihydro-1,4-benzoxazin-4-yl)methylbenzofuran-5-yl]-2-ethoxypropanol acid, ethyl ester

The specified connection (0.8 g, 58%) was obtained in the form of a resinous substance of 5-formyl-2-(2,3-dihydro-1,4-benzoxazin-4-yl)methylbenzofuran (1.0 g, to 3.41 mmol) using the procedure similar to that described in example 1.

1H-NMR (CDCl3, 200 MHz): δ 1,06 and 1.38 (6N, co2CH3and co2CH3, triplet signals)of 3.48 (t, J=4,98 Hz, 2H), 3,89-4,18 (complex, 2H), 4,28-4,40 (complex, 4H), 4,54 and 4,56 (United 2N signals-NCH2), 6,20 (0,5H, olefinic proton isomer (E)of 6.52 and 6,59 (United, 1H), 6,65-6,83 (complex 2,5H), 7,08-7,11 (complex, 1H), 7,32-7,44 (complex, 2H), 7,69 (d, J=8,30 Hz, 1H), to 7.99 (s, 1H).

EXAMPLE 4

(E/Z)-3-[4-[2-(2,3-Dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid, ethyl ester

The specified connection was obtained as a mixture of geometric isomers in a ratio of 38:62 (data1H-NMR) (3.2 g, 71%) as a resinous mass of 4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]benzaldehyde (3.3 g, 11,03 mmol)obtained by the method described in intermediate synthesis of 2 and described in international publication WO 98/52946, according to the method similar to that described in example 1.

1H-NMR (CDCl3, 200 MHz): δ to 1.14 and 1.35 (United, 6N, isomers CCH2CH3, triplet signals)to 3.02 (t, J=4,90 Hz, 2H), 3,69-3,88 (complex, 4H), 3,92-a 4.03 (complex, 2H), 4,12-4,33 (complex, 4H), the 6.06 (s, 0,S, olefinic proton isomer (E)6,61-7,14 (C is, 6,N), 7,73 (d, J=8,81 Hz, 2H).

EXAMPLE 5

(±)3-[2-(2,3-Dihydro-1,4-benzoxazin-4-yl)methylbenzofuran-5-yl]-2-ethoxypropanol acid, methyl ester

The specified connection (0.6 g, 78%) was obtained as a resinous mass of the ethyl ester of (E/Z)-3-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)methylbenzofuran-5-yl]-2-ethoxypropanol acid (0.8 g, a 1.96 mmol)obtained in example 3 by the procedure similar to that described in example 2.

1H-NMR (CDCl3, 200 MHz): δ to 1.15 (t, J=7,00 Hz, 3H), of 3.07 (d, J=5,80 Hz, 2H), 3,28-3,67 (complex, 4H), 3,70 (s, 3H), a 4.03 (t, J=6,00 Hz, 1H), 4,28 (t, J=4,47 Hz, 2H), of 4.54 (s, 2H), of 6.52 (s, 1H), 6,62-6,89 (complex, 4H), 7,10 (d, J=7,05 Hz, 1H), 7,35 (complex, 2H).

EXAMPLE 6

(±)3-[4-[2-(2,3-Dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid, methyl ester

The specified connection (2.3 g, 76%) was obtained in the form of a resinous liquid of ethyl ester of (E/Z)-3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid (3.1 g, 7,50 mmol)obtained in example 4 by the procedure similar to that described in example 2.

1H-NMR (CDCl3, 200 MHz): δ to 1.15 (t, J=7.01 Hz, 3H), of 2.93 (d, J=6,65 Hz, 2H), 3,03 (t, J=to 5.21 Hz, 2H), 3,23-to 3.41 (complex, 1H), 3,52-3,80 (complex, 8H), of 3.97 (t, J=7.01 Hz, 1H), 4,14 (t, J=of 5.81 Hz, 2H), 6,61-6,82 (complex, 4H), 6,92-7,05 (complex, 2H), 7,13 (d, J=8.53 Hz, 2H).

EXAMPLE 7

(±)2-Methyl-3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)who toxi]phenyl]-2-ethoxypropanol acid, methyl ether

Methyl ether (±)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid (0.6 g, 1.5 mmol)obtained in example 2, was dissolved in anhydrous tetrahydrofuran (5 ml) and the resulting solution was added diisopropylamide lithium (the 5.25 ál, 0.5 ml solution in THF/hexane) at -78°C. was Stirred 1 hour at -78°C, after which was added methyliodide (0.75 ml), warmed to room temperature (about 25° (C) and stirred for another 20 hours at this temperature. Was added water (20 ml), acidified with 1N hydrochloric acid and was extracted with ethyl acetate (2×25 ml). Layers of ethyl acetate were combined, washed with water (25 ml) and saturated NaCl solution (25 ml), dried (Na2SO4), filtered and the solvent evaporated under reduced pressure, obtaining mentioned in the title compound (0.5 g, 80%) as oil.

1H-NMR (CDCl3, 200 MHz): δ to 1.21 (t, J=6,97 Hz, 3H), of 1.31 (s, 3H), 2.95 and (s, 2H), 3,32-to 3.58 (complex, 4H), 3,62-3,84 (complex, 5H), 4,14 (t, J=of 5.81 Hz, 2H), 4,22 (t, J=4,25 Hz, 2H), 6,55-6,88 (complex, 6N), was 7.08 (d, J=8,63 Hz, 2H).

EXAMPLE 8

(±)2-(2-Forebesi)-3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]-phenyl]-2-ethoxypropanol acid, methyl ester

The specified connection (0.6 g, 78%) was obtained as a brown liquid of methyl ester (±)3-[4-[2-(2,3-dihydro-1,4-Ben is oxazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid (0.6 g, 1.5 mmol)obtained in example 2 by the method similar to that described in example 7.

1H-NMR (CDCl3, 200 MHz): δ to 1.22 (t, J=of 6.96 Hz, 3H), 3,03-3,18 (complex, 4H), 3,51 (t, J=4,20 Hz, 2H), 3,59-3,71 (complex, 7H), 4,14 (t, J=of 5.81 Hz, 2H), 4,22 (t, J=4,24 Hz, 2H), 6.42 per-6,85 (complex, 6N), 6,90-7,32 (complex, 6N).

EXAMPLE 9

(E/Z)-3-[4-[2-(3-Oxo-2H-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid, ethyl ester

The specified connection (3,9 g, 97%) was obtained as a mixture of isomers E/Z ratio of 32:68 in the form of a white solid from 4-[2-(3-oxo-2H-1,4-benzoxazin-4-yl)ethoxy]benzaldehyde (2.9 g, 9.7 mmol)obtained in the intermediate synthesis of 1, by the method similar to that described in example 1. TPL 92-95°C.

1H-NMR (CDCl3, 200 MHz): δ 1,13-1,43 (complex, 6N), 3,88-was 4.02 (complex, 2H), 4,07-4,40 (complex, 6N), 4,60 (s, 2H), equal to 6.05 (s, 0,32H, olefinic proton isomer (E)6,76-7,32 (complex, 6,N), 7,71 (d, J=8,72 Hz, 2H).

EXAMPLE 10

(±)3-[4-[2-(3-Oxo-2H-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid, methyl ester

The specified connection (1.0 g, 51%) was obtained as colorless syrup of ethyl ester of (E/Z)-3-[4-[2-(3-oxo-2H-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid (2.0 g, 4.8 mmol)obtained in example 9 by the method similar to that described in example 2.

1H-NMR (CDCl3, 00 MHz): δ to 1.14 (t, J=7,00 Hz, 3H), of 2.92 (d, J=6,60 Hz, 2H), 3.25 to 3,41 (complex, 1H), 3,53-3,61 (complex, 1H), 3,68 (s, 3H), of 3.96 (t, J=7,00 Hz, 1H), 4,21-4,32 (complex, 4H), and 4.68 (s, 2H), 6,77 (d, J=8,63 Hz, 2H), 6,98-7,33 (complex, 6N).

EXAMPLE 11

(E/Z)-3-[6-[2-(2,3-Dihydro-1,4-benzothiazin-4-yl)ethoxy]naphthyl]-2-ethoxypropanol acid, ethyl ester

The specified connection was obtained as a mixture of isomers E/Z ratio of 1:1 (1,74 g, 87%) as a brown syrup of 6-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]naphthaldehyde (1.5 g, 4,29 mmol)obtained in the intermediate synthesis of 3, by the method similar to that described in example 1.

1H-NMR (CDCl3, 200 MHz): δ 0,99 to 1.47 (complex, 6N), 3,06 (t, J=4,98 Hz, 2H), 3,79-3,95 (complex, 4H), 3,99-4,18 (complex, 2H), 4,25-4,37 (complex, 4H), 6,23 (s, 0,5H, olefinic proton isomer (E)6,59-6,79 (complex, 2H), 6,97-7,29 (complex, 4,5H), EUR 7.57-7,95 (complex, 3H), to 8.14 (s, 1H).

EXAMPLE 12

(±)3-[6-[2-(2,3-Dihydro-1,4-benzothiazin-4-yl)ethoxy]naphthyl]-2-ethoxypropanol acid, methyl ester

The specified connection (1.25 g, 75%) was obtained as colorless syrup of ethyl ester of (E/Z)-3-[6-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]naphthyl]-2-ethoxypropanol acid (1.7 g, to 3.67 mmol)obtained in example 11 by the method similar to that described in example 2.

1H-NMR (CDCl3, 200 MHz): δ to 1.14 (t, J=7,06 Hz, MN), 3,06 (t, J=to 5.21 Hz, 2H), 3,13 (d, J=7,15 Hz, 2H), 3,29-3,3 (complex, 1H), 3,57-3,64 (complex, 1H), 3,70 (s, 3H), of 3.77-3,83 (complex, 4H), 4.09 to (t, J=7,20 Hz, 1H), 4,25 (t, J=of 5.81 Hz, 2H), 6,62-6,79 (complex, 2H), of 6.96 and 7.36 (complex, 5H), 7,60-7,70 (complex, 3H).

EXAMPLE 13

(±)3-[4-[2-(2,3-Dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-hydroxypropanoic acid, ethyl ester

The specified connection (0.14 g, 32%) was obtained in the form of a resinous liquid from 2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethylmethanesulfonate (0.36 g, of 1.42 mmol), potassium carbonate (0,80 g, 5.8 mmol) and ethyl ester of 2-hydroxy-3-(4-hydroxyphenyl)propanoic acid (0.3 g, of 1.42 mmol)using the conditions similar to those described in intermediate synthesis 2.

1H-NMR (CDCl3, 200 MHz): δ to 1.24 (t, J=7,15 Hz, 3H), 2,71 (d, J=6,23 Hz, 1H, exchanges with D2O)2,84-3,10 (complex, 2H), 3,50 (t, J=4,47 Hz, 2H), to 3.67 (t, J=5,48 Hz, 2H), 4,11-4.26 deaths (complex, 6N), 4,37-4,39 (complex, 1H), 6,61-6,86 (complex, 6N), 7,11 (d, J=8,62 Hz, 2H).

EXAMPLE 14

(±)3-[4-[2-(2,3-Dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-hydroxypropanoic acid, ethyl ester

The specified connection (1.9 g, 17%) was obtained in the form of a resinous liquid from 2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethylmethanesulfonate (8,2 g, 30.0 mmol), potassium carbonate (20.7 g, 150 mmol) and ethyl ester of 2-hydroxy-3-(4-hydroxyphenyl)propanoic acid (6.3 g, 30.0 mmol)using the conditions similar to those described in intermediate synthesis 2.

1H-I Is R (CDCl 3, 200 MHz): δ of 1.29 (t, J=7,11 Hz, 3H), 2,70-2,80 (broadened, 1H, exchanges with D2O), 2,82-3,15 (complex, 4H), 3,65-3,82 (complex, 4H), 4,10-4,30 (complex, 4H), 4,28-4,40 (complex, 1H), 6,62-6,89 (complex, 4H), 6,92-7,18 (complex, 4H).

EXAMPLE 15

(±)3-[4-[2-(2,3-Dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-benzyloxypropionic acid, ethyl ester

In a cooled ice suspension of sodium hydride (60% dispersion in oil) (0.08 g, of 1.66 mmol) in anhydrous dimethylformamide (3 ml) with stirring under nitrogen atmosphere was added a solution of ethyl ester (±)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-hydroxypropanoic acid (0.5 g, of 1.34 mmol)obtained in example 13, in anhydrous dimethylformamide (5 ml). The reaction mixture was stirred for 30 minutes at 0°and then added benzylbromide (0,46 g, 2,69 mmol). The mixture was heated to 25°C and stirred for another 18 hours. Was added water (25 ml) and was extracted with ethyl acetate (2×50 ml). The organic layers were combined, washed with water (50 ml) and saturated NaCl solution (50 ml), dried (Na2SO4) and filtered. The solvent is evaporated under reduced pressure, and the residue was subjected to chromatography on silica gel using a mixture of ethyl acetate and petroleum ether (2:8) as eluent, obtaining mentioned in the title compound (0.3 g) with 3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]the dryer is l]-2-benzyloxypropionic. This mixture (1:1) used in example 47, without separating the components.

1H-NMR (CDCl3, 200 MHz): δ of 1.23 (t, J=7,05 Hz, 1,5H), 2,99 (d, J=7,06 Hz, 4H), 3.00 and-3,72 (complex, 8H), 4,05-4,30 (complex N), 4,32-4,71 (complex, 4H), to 5.13 (s, 2H), 6,55-6,89 (complex N), 7,05 and 7.36 (complex N).

EXAMPLE 16

(±)3-[4-[2-(2,3-Dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-butoxypropan acid, ethyl ester

The specified connection (0.4 g, 52%) was obtained in the form of a resinous liquid from 2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethylmethanesulfonate (0,46 g, 1.78 mmol), potassium carbonate (0,98 g, 7,12 mmol) and ethyl ester of 2-butoxy-3-(4-hydroxyphenyl)propanoic acid (0,47 g, 1.78 mmol)using the conditions similar to those described in intermediate synthesis 2.

1H-NMR (CDCl3, 200 MHz): δ 0,84 (t, J=7,53 Hz, 3H), 1,19-1,34 (complex, 5H), 1,43-1.55V (complex, 2H), 2,92 (d. J=6,32 Hz, 2H), 3,22-3,36 (complex, 1H), 3,48-3,59 (complex, ZN), 3,68 (t, J=of 5.82 Hz, 2H), 3,93 (t, J=6,20 Hz, 1H), 4,11-4,24 (complex, 6N), 6,61-6,86 (complex, 6N), 7,13 (d, J=8,30 Hz, 2H).

EXAMPLE 17

(±)3-[4-[2-(2,3-Dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-hexyloxyphenol acid, ethyl ester

The specified connection (0.31 g, 50%) was obtained as colorless syrup of 2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethylmethanesulfonate (0.35 g, 1.3 mmol), potassium carbonate (0.75 g, 5.4 mmol) and ethyl ester of 2-hexyloxy-3-(4-hydro is Setenil)propanoic acid (0.4 g, 1.3 mmol)using the conditions similar to those described in intermediate synthesis 2.

1H-NMR (CDCl3, 200 MHz): δ of 0.85 (t, J=5,72 Hz, 3H), of 1.20 to 1.34 (complex, 7H), 1,40-1,66 (complex, 4H), of 2.93 (d, J=6,00 Hz, 2H), 3,21-3,31 (complex, 1H), 3,49-3,60 (complex, 3H), 3,68 (t, J=5,72 Hz, 2H), 3,93 (t, J=of 5.81 Hz, 1H), 4,11-4,24 (complex, 6N), 6,62-for 6.81 (complex, 5H), 7,09-7,16 (complex, 3H).

EXAMPLE 18

(E/Z)-3-[4-[2-(2,3-Dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-phenoxypropanol acid, ethyl ester

The specified connection (0,92 g, 58%) was obtained as a mixture of isomers E/Z (40:60) in the form of a resinous liquid from 4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]benzaldehyde (1.0 g, 3.0 mmol) and triethyl-2-phenoxypropionate (A.G.Schultz et al., J.Org. Chem., 1983, 48, 3408) (1,3 g, 4.0 mmol) using the procedure similar to that described in example 1.

1H-NMR (CDCl3, 200 MHz): δ of 1.06 and 1.18 (combined 3H, isomeric och2CH3, triplet signals), 3,43 is 3.57 (complex, 2H), 3,64-3,75 (complex, 2H), 4,06-4,28 (complex, 6N), 6,60-of 6.90 (complex, 8H), 6,94-7,12 (complex, 2H), 7,22 was 7.45 (complex, 3H), of 7.64 (d, J=8,72 Hz, 1H).

EXAMPLE 19

(±)3-[4-[2-(2,3-Dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-phenoxypropanol acid, methyl ester

The specified connection (0,49 g, 57%) was obtained as a resinous mass of the ethyl ester of (E/Z)-3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-phenoxypropan the howling acid (0.9 g, 2.0 mmol)obtained in example 18, the method similar to that described in example 2.

1H-NMR (CDCl3, 200 MHz): δ 3,17 (d, J=6,20 Hz, 2H), 3,50 (t, J=4,30 Hz, 2H), 3,65-3,70 (complex, 5H), 4,14 (t, J=USD 5.76 Hz, 2H), 4,21 (t, J=4,15 Hz, 2H), and 4.75 (t, J=6,40 Hz, 1H), 6.61-6,98 (complex N), 7,17-7,27 (complex, 4H).

EXAMPLE 20

(E/Z)-3-[4-[2-(2,3-Dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-phenoxypropanol acid, ethyl ester

The specified connection (3.7 g, 60%) was obtained as a mixture of isomers E/Z (35:65) as a resinous mass of 4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]benzaldehyde (4.0 g, 13,0 mmol) and triethyl-2-phenoxypropionate (A.G.Schultz et al., J.Org. Chem., 1983, 48, 3408) (5,07 g, 16.0 mmol) by a similar method to that described in example 1.

1H-NMR (CDCl3, 200 MHz): δ 1,05-1,36 (complex, 3H), 3.00 and-3,11 (complex, 2H), 3,64-3,85 (complex, 4H), 4.09 to 4,30 (complex, 4H), 6,58-7,13 (complex, 8H), 7,20-7,46 (complex, 4H), of 7.65 (d, J=to 8.70 Hz, 2H).

EXAMPLE 21

(±)3-[4-[2-(2,3-Dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-phenoxypropanol acid, methyl ester

The specified connection (2.3 g, 64%) was obtained as a resinous mass of the ethyl ester of (E/Z)-3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-phenoxypropionic acid (3.7 g, 8.0 mmol)obtained in example 20, by the method similar to that described in example 2.

1H-NMR (CDCl3, 200 MHz: δ to 2.99 (t, J=5.43 Hz, 2H)and 3.15 (d, J=5,99 Hz, 2H), 3,60-3,78 (complex, 7H), of 4.13 (t, J=5,40 Hz, 2H), 4,74 (t, J=6,23 Hz, 1H), 6,58-6,89 (complex, 6N), 6,90-7,06 (complex, 2H), 7,11-7,30 (complex, 5H).

EXAMPLE 22

(E/Z)-3-[4-(4-Methyl-3,4-dihydro-1,4-benzoxazin-2-yl)methoxyphenyl]-2-ethoxypropanol acid, ethyl ester

The specified connection (0.4 g, 25%) was obtained as a mixture of isomers E/Z (1:1) as a brown liquid from 4-(4-methyl-3,4-dihydro-1,4-benzoxazin-2-yl]methoxybenzaldehyde (1.2 g, 4,24 mmol)obtained in the intermediate synthesis of 4, by the method similar to that described in example 1.

1H-NMR (CDCl3, 200 MHz): δ of 1.36 (t, J=7,10 Hz, 6N), 2,90 (s, 3H), 3,26 is-3.45 (complex, 2H), 3,99 (q, J=7,20 Hz, 2H), 4,10-to 4.38 (complex, 4H), 4,50-4,60 (complex, 1H), 6,70 (d, J=7,47 Hz, 2H), for 6.81-6.90 to (complex, 5H), of 7.75 (d, J=8,80 Hz, 2H).

EXAMPLE 23

(±)3-[4-(4-Methyl-3,4-dihydro-1,4-benzoxazin-2-yl)methoxyphenyl]-2-ethoxypropanol acid, methyl ester

The specified connection (0.25 g, 65%) was obtained as a thick liquid from the ethyl ester of (E/Z)-3-[4-(4-methyl-3,4-dihydro-1,4-benzoxazin-2-yl)methoxyphenyl]-2-ethoxypropanol acid (0.4 g, 1.0 mmol)obtained in example 22, by the method similar to that described in example 2.

1H-NMR (CDCl3, 200 MHz): δ to 1.16 (t, J=7,00 Hz, 3H), 2,89 (s, 3H), 2.95 points (d, J=6,20 Hz, 2H), 3,19-to 3.41 (complex, 3H), 3,55-3,66 (complex, 1H), 3,70 (s, 3H), 3.95 to 4,24 (complex, 3H), 4,60 with 4.64 complex, 1H), 6,64-7,08 (complex, 6N), to 7.15 (d, J=8,40 Hz, 2H).

EXAMPLE 24

(E/Z)-3-[4-(4-Benzyl-3,4-dihydro-1,4-benzoxazin-2-yl)methoxyphenyl]-2-ethoxypropanol acid, ethyl ester

The specified connection (3.0 g, 76%) was obtained as a mixture of isomers E/Z (1:1) in the form of a viscous liquid of 4-(4-benzyl-3,4-dihydro-1,4-benzoxazin-2-yl]methoxybenzaldehyde (3.0 g, 8,35 mmol)obtained in the intermediate synthesis of 5, according to the method similar to that described in example 1.

1H-NMR (CDCl3, 200 MHz): δ 1,33-1,40 (complex, 6N), 3,39-3,44 (complex, 2H), 3,99 (q, J=7,00 Hz, 2H), 4,11-to 4.38 (complex, 4H), to 4.46 (d, J=5,00 Hz, 2H), to 4.52-4,66 (complex, 1H), 6,60-6,97 (complex, 7H), 7,28 (s, 5H), of 7.75 (d, J=8,80 Hz, 2H).

EXAMPLE 25

(±)3-[4-(4-Benzyl-3,4-dihydro-1,4-benzoxazin-2-yl)methoxyphenyl]-2-ethoxypropanol acid, methyl ester

The specified connection (1.5 g, 100%) was obtained from ethyl ester of (E/Z)-3-[4-(4-benzyl-3,4-dihydro-1,4-benzoxazin-2-yl)methoxyphenyl]-2-ethoxypropanol acid (1.5 g, 3,17 mmol)obtained in example 24, by the method similar to that described in example 2.

1H-NMR (CDCl3, 200 MHz): δ of 1.17 (t, J=7,00 Hz, 3H), 2,96 (d, J=6,60 Hz, 2H), 3,31 is 3.57 (complex, 3H), 3,60-3,70 (complex, 1H), 3,71 (s, 3H), of 3.97-4.26 deaths (complex, 3H), 4,47 (d, J=4,00 Hz, 2H), 4,56-br4.61 (complex, 1H), 6,68-of 6.90 (complex, 6N), 7,15 (d, J=8,50 Hz, 2H), 7,29 (s, 5H).

EXAMPLE 26

(±)3-[4-[2-(2,3-Dihydro-1,4-benzoxazin-4 and is)ethoxy]phenyl]-2-ethoxypropanol acid

Methyl ether (±)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid (4.7 g, 12.2 mmol)obtained in example 2 was dissolved in methanol (50 ml) and the resulting solution was added 10% NaOH solution (28 ml). The mixture was stirred at 25°C for 3 hours. The solvent was removed under reduced pressure, and the residue was acidified with 2N hydrochloric acid and was extracted with ethyl acetate (2×100 ml). Layers of ethyl acetate were combined, washed with water (75 ml) and saturated NaCl solution (50 ml), dried (Na2SO4), filtered and the solvent evaporated under reduced pressure. The residue was subjected to chromatography on silica gel using ethyl acetate, getting mentioned in the title compound (3.0 g, 66%) as a viscous liquid.

1H-NMR (CDCl3, 200 MHz): δ of 1.17 (t, J=of 6.96 Hz, 3H), 2,85-3,12 (complex, 2H), 3,40-3,61 (complex, 4H), of 3.69 (t, J=5,72 Hz, 2H), Android 4.04 (dd, J=7,38 and 4,27 Hz, 1H), 4,10-4,28 (complex, 4H), 6,52-6,85 (complex, 6N), 7,14 (d, J=at 8.60 Hz, 2H), COOH proton is not detected from by broadening the peak.

EXAMPLE 27

(±)3-[4-[2-(2,3-Dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid, sodium salt

A mixture of (±)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid (0.15 g, 0.4 mmol)obtained in example 26, and sodium methoxide (23,4 mg) in m is canola (5 ml) was stirred at 25° C for 2 hours. The solvent was removed and the residue was treated with anhydrous ether (3×10 ml). The precipitation was filtered off, washed with anhydrous ether (2×5 ml) and dried over P2O5under vacuum, obtaining mentioned in the title compound (0.12 g, 75%) as a colourless hygroscopic solid.

1H-NMR (DMSO-d6, 200 MHz): δ and 0.98 (t, J=6,83 Hz, 3H), 2,60-2,69 (complex, 1H), 2,78-2,92 (complex, 1H), 3,05-3,21 (complex, 2H), 3,41-3,75 (complex, 5H), 4,08-4,21 (complex, 4H), of 6.49-6,85 (complex, 6N), 7,12 (d, J=8,30 Hz, 2H).

EXAMPLE 28

(±)3-[2-(2,3-Dihydro-1,4-benzoxazin-4-yl)methylbenzofuran-5-yl]-2-ethoxypropanol acid

The specified connection (0.5 g, 87%) was obtained as a resinous mass of methyl ester (±)3-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)methylbenzofuran-5-yl]-2-ethoxypropanol acid (0.6 g and 1.51 mmol)obtained in example 5 by the procedure similar to that described in example 26.

1H-NMR (CDCl3, 200 MHz): δ of 1.26 (t, J=7,06 Hz, 3H), 3,05 of 3.28 (complex, 2H), 3,40-3,68 (complex, 4H), 4.09 to (dd, J=7,47 and are 4.24 Hz, 1H), 4,28 (t, J=4,15 Hz, 2H), 4.53-in (s, 2H), of 6.52 (s, 1H), 6,60-of 6.90 (complex, 4H), 7,13 (d, J=to 8.70 Hz, 1H), to 7.32 and 7.36 (complex, 2H), COOH proton is not detected due to the broadening of the peak.

EXAMPLE 29

(±)3-[4-[2-(2,3-Dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid

The specified connection is out (1.4 g, 63%) was obtained as a resinous mass of methyl ester (±)3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid (2.3 g, 5,73 mmol)obtained in example 6, by the method similar to that described in example 26.

1H-NMR (CDCl3, 200 MHz): δ of 1.18 (t, J=7,00 Hz, 3H), 2,82-3,15 (complex, 4H), 3,40-3,68 (complex, 2H), 3,70-3,81 (complex, 4H), of 4.05 (dd, J=7.29 trend and to 4.33 Hz, 1H), 4,16 (t, J=5,72 Hz, 2H), 6,68-6,74 (complex, 2H), for 6.81 (d, J=8,50 Hz, 2H), 6,94-7,06 (complex, 2H), 7,14 (d, J=8,50 Hz, 2H), COOH proton is not detected due to the broadening of the peak.

EXAMPLE 30

(±)3-[4-[2-(2,3-Dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid, sodium salt

The specified connection (0,42 g, 81%) was obtained as a colourless solid from (±) 3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid (0.5 g, of 1.30 mmol)obtained in example 29, by the method similar to that described in example 27.

1H-NMR (CDCl3, 200 MHz): δ and 0.98 (t, J=7,00 Hz, 3H), 2,72-3,25 (complex, 5H), 3,30-3,51 (complex, 1H), 3,61-to 3.73 (complex, 4H), 3,82-3,91 (complex, 1H), Android 4.04 (t, J=5,72 Hz, 2H), 6,52-6,79 (complex, 4H), 6,91-7,03 (complex, 2H), 7,10 (d, J=8,40 Hz, 2H).

EXAMPLE 31

(±)3-[4-[2-(2,3-Dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-ethoxypropane

Oxalicacid (of 0.28 ml, 3.1 mmol) and (±)3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)etox is]phenyl]-2-ethoxypropanol acid (0.6 g, 1.55 mmol)obtained in example 29 was dissolved in anhydrous dichloromethane (10 ml) and boiled under reflux for 2 hours. The solvent and excess oxalicacid was removed under reduced pressure. The residue was dissolved in dichloromethane, was added aqueous ammonia (5 ml) and was stirred for 30 minutes. The reaction mixture was extracted with chloroform (2×25 ml). Layers of chloroform were combined, washed with water (25 ml), dried (Na2SO4was filtered and the solvent evaporated under reduced pressure. The residue was subjected to chromatography on silica gel using a mixture of ethyl acetate and petroleum ether (7:3) as eluent, obtaining mentioned in the title compound (0.32 g, 54%) as a white solid with TPL 120-122°C.

1H-NMR (CDCl3, 200 MHz): δ to 1.15 (t, J=of 6.96 Hz, 3H), 2,81-3,20 (complex, 4H), 3,38-to 3.58 (complex, 2H), 3,71-3,90 (complex, 4H), 3,91 (dd, J=7,38 and to 3.73 Hz, 1H), 4,16 (t, J=5,58 Hz, 2H), 5,54 (bs, exchanges with D2O, 1H), 6,44 (bs, exchanges with D2O, 1H), 6,59-6,84 (complex, 4H), 6,92-7,19 (complex, 4H).

EXAMPLE 32

(±)N-Methyl-3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-ethoxypropane

In a cooled ice solution (±)3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)-ethoxy]phenyl]-2-ethoxypropanol acid (0.3 g, 0.78 mmol)obtained in example 29, and triethylamine (rate £ 0.162 g, 1.6 mmol) in anhydrous chloromethane (10ml) was added pivaloate (0.10 g, 0.86 mmol) and stirred for 30 minutes at 0°C. To this reaction mixture was added methylamine (40% solution) (0,124 ml) at 25°C and stirred for another 1 hour at 25°C. was Added water (20 ml) and was extracted with ethyl acetate (2×20 ml). The organic extracts were combined, washed with water (10 ml) and saturated NaCl (10 ml), dried (Na2SO4), filtered and the solvent evaporated under reduced pressure. The residue was subjected to chromatography on silica gel using a mixture of ethyl acetate and petroleum ether (1:1), obtaining mentioned in the title compound as a colourless solid with TPL 80-82°C.

1H-NMR (CDCl3, 200 MHz): δ a 1.11 (t, J=7,00 Hz, 3H), was 2.76 (d, J=4,89 Hz, 3H), 2,81-2,88 (complex, 1H), 3,01-3,12 (complex, 3H), 3,39-3,52 (complex, 2H), 3,70-3,81 (complex, 4H), 3,86-3,91 (complex, 1H), 4,14 (t, J=of 5.81 Hz, 2H), 6.48 in (bs, 1H), 6,61-for 6.81 (complex, 4H), 6,94-7,14 (complex, 4H).

EXAMPLE 33

(±)3-[4-[2-(2,3-Dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropane

The specified connection (0.2 g, 80%) was obtained as a white solid from (±) 3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid (0.25 g, 0.67 mmol)obtained in example 26, and ammonia solution (4 ml) using the procedure similar to that described in example 31. TPL 107-109°C.

1H-NMR (CDCl3, 200 MHz): δ of 1.13 (t, J=of 6.96 Hz, 3H), 2,81-2,93(complex, 1H), 3,03-3,19 (complex, 1H), 3,34-3,59 (complex, 4H), of 3.69 (t, J=of 5.53 Hz, 2H), 3,88 (dd, J=7,43 and 3.70 Hz, 1H), 4,15 (t, J=5,58 Hz, 2H), 4,28 (t, J=4,24 Hz, 2H), 5,49 (bs, 1H, exchanges with D2O)to 6.43 (bs, 1H, exchanges with D2O)6,68-6,87 (complex, 6N), to 7.15 (t, J=8,49 Hz, 2H).

EXAMPLE 34

(±)N-Methyl-3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropane

The specified connection (0,23 g, 74%) was obtained as a white solid from (±)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy] phenyl]-2-ethoxypropanol acid (0.3 g, 0.8 mmol)obtained in example 26, and methylamine (40% solution) (2 ml) using the procedure similar to that described in example 32. TPL 97-99°C.

1H-NMR (CDCl3, 200 MHz): δ to 1.14 (t, J=7,00 Hz, 3H), was 2.76 (d, J=4,98 Hz, 3H), 3,02-3,14 (complex, 1H), 3,35 is-3.45 (complex, 2H), 3,52 (t, J=4,57 Hz, 2H), 3,68 (t, J=of 5.81 Hz, 2H), 4,14 (t, J=5,72 Hz, 2H), 4,22 (t, J=4,15 Hz, 2H), 4,80-4,90 (complex, 1H), 6,50 (bs, 1H), 6,55-6,89 (complex, 6N), 7,11 (d, J=8,3 Hz, 2H), 7,88 (dd, J=7,06 and 3.74 Hz, 1H).

EXAMPLE 35

(±)N-Benzyl-3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropane

The specified connection (0.25 g, 67%) was obtained as a white solid from (±)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid (0.3 g, 0.8 mmol)obtained in example 26, and benzylamine (0,095 g, 0.88 mmol) using the procedure similar to that described in example 32. TPL 94-96°C.

1H-NMR (CDCl 3, 200 MHz): δ a 1.11 (t, J=7,00 Hz, 3H), 2,82-3,18 (complex, 2H), 3,40-3,55 (complex, 4H), 3,70 (t, J=5,49 Hz, 2H), 3,94-3,98 (complex, 1H), 4,14 (t, J=5,72 Hz, 2H), 4,23 (t, J=4,24 Hz, 2H), 4,28-to 4.52 (complex, 2H), 6,60-6,87 (complex, 6N), 7,06-7,32 (complex, 7H), proton CONH not determined due to the broadening of the peak.

EXAMPLE 36

(±)N-Benzyl-3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-ethoxypropane

The specified connection (0,22 g, 74%) was obtained as a white solid from (±)3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid (0.25 g, of 0.65 mmol)obtained in example 29, and benzylamine (0,076 g, 0.71 mmol) by the method similar to that described in example 32. TPL 92-93°C.

1H-NMR (CDCl3, 200 MHz): δ to 1.15 (t, J=7,00 Hz, 3H), 2,88-3,20 (complex, 4H), 3,42-3,60 (complex, 2H), of 3.73-a 3.87 (complex, 4H), 3,98-4,06 (complex, 1H), 4,18 (t, J=5,72 Hz, 2H), 4,30-4,56 (complex, 2H), 6,61-of 6.90 (complex, 4H), 7,00-7,43 (complex N), proton CONH not defined due to the broadening of the peak.

EXAMPLE 37

(±)2-Methyl-3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid

The specified connection (0.3 g, 62%) was obtained in the form of a layered fluid from the methyl ester (±)2-methyl-3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid (0.5 g, 1.2 mmol)obtained in example 7, according to the method similar to the one that is painted in example 26.

1H-NMR (CDCl3, 200 MHz): δ 1.24 (the complex, 6N), 2,98 and 3.04 (1H, 2d, J=14.1 Hz each), 3,51 (t, J=4,25 Hz, 2H), 3,49-3,71 (complex, 4H), to 4.15 (t, J=5,63 Hz, 2H), 4,22 (t, J=4,48 Hz, 2H), 6,60-6,87 (complex, 6N), 7,07 (d, J=8,67 Hz, 2H), proton COOH is not defined due to the broadening of the peak.

EXAMPLE 38

(±)2-Methyl-3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid, sodium salt

The specified connection (0.12 g, 51%) was obtained as a white solid from (±)2-methyl-3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid (0,22 g, or 0.57 mmol)obtained in example 37, by the method similar to that described in example 27.

1H-NMR (DMSO-d6, 200 MHz): δ 0,96-1,08 (complex, 6N), and 2.79 (s, 2H), 3,28-3,52 (complex, 4H), to 3.64 (t, J=and 5.30 Hz, 2H), 4,05-4;19 (complex, 4H), 6.48 in-6,59 (complex, 1H), 6,62-6,86 (complex, 4H), 7.03 is-7,28 (complex, 3H).

EXAMPLE 39

(±)2-(2-Forebesi)-3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid

The specified connection (0.25 g, 42%) was obtained in the form of a resinous liquid of methyl ester (±)2-(2-forebesi)-3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid (0.6 g, 1.2 mmol)obtained in example 8 by the method similar to that described in example 26.

1H-NMR (CDCl3, 200 MHz): δ of 1.12 (t, J=PC 6.82 Hz,3H), of 1.65 (bs, 1H, exchanges with D2O), 3,11-3,42 (complex, 4H), 3,50 (t, J=4,34 Hz, 2H), 3,68 (t, J=5,67 Hz, 2H), 3,70-3,89 (complex, 2H), 4,14 (t, J=5,67 Hz, 2H), 4,21 (t, J=4,15 Hz, 2H), 6,62-6,86 (complex, 6N), 7,03-7,12 (complex, 4H), 7.18 in-7,30 (complex, 2H).

EXAMPLE 40

(±)2-(2-Forebesi)-3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid, sodium salt

The specified connection (0.11 g, 48%) was obtained as a white solid from (±)2-(2-forebesi)-3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]-phenyl]-2-ethoxypropanol acid (0,22 g, 0.45 mmol)obtained in example 39, according to the method similar to that described in example 27.

1H-NMR (CDCl3, 200 MHz): δ of 1.02 (t, J=of 6.65 Hz, 3H), 2,75-2,92 (complex, 4H), 3,39-to 3.58 (complex, 4H), 3,62 (bs, 2H), 4.04 the-4,20 (complex, 4H), of 6.49-6,82 (complex, 5H), 6.90 to-7,28 (complex, 6N), 7,49-7,13 (complex, 1H).

EXAMPLE 41

(±)3-[4-[2-(3-Oxo-2H-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid

The specified connection (0.75 g, 77%) was obtained as a white solid from methyl ester (±)3-[4-[2-(3-oxo-2H-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid (1.0 g, 2.5 mmol)obtained in example 10, according to the method similar to that described in example 26. TPL 90-93°C.

1H-NMR (CDCl3, 200 MHz): δ of 1.18 (t, J=of 6.96 Hz, 3H), 2,88-3,13 (complex, 2H), 3,41-3,63 (complex, 2H), 4,06 (dd, J=743 and 4,33 Hz, 1H), 4,25-to 4.52 (complex, 4H), br4.61 (s, 2H), 6,80 (d, J=8,62 Hz, 2H), 7,00-7,34 (complex, 6N), 7,18-7,30 (complex, 2H), COOH proton is not detected due to the broadening of the peak.

EXAMPLE 42

(±)3-[4-[2-(3-Oxo-2H-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid, sodium salt

The specified connection (0.12 g, 56%) was obtained as a white solid from (±) 3-[4-[2-(3-oxo-2H-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid (0.2 g, 0.51 mmol)obtained in example 41, according to the method similar to that described in example 27.

1H-NMR (CDCl3, 200 MHz): δ 0,99 (t, J=6,97 Hz, 3H), 2,61-2,80 (complex, 2H), 3,32 is 3.57 (complex, 1H), 3,60-3,72 (complex, 1H), 3,65-3,70 (complex, 1H), 4,18 (bs, 2H), 4,30 (bs, 2H), and 4.68 (s, 2H), 6,78 (d, J=8,4 Hz, 2H), 7.03 is-7,14 (complex, 5H), 7,42 (d, J=7,06 Hz, 1H).

EXAMPLE 43

(±)3-[6-[2-(2,3-Dihydro-1,4-benzothiazin-4-yl)ethoxy]naphthyl]-2-ethoxypropanol acid

The specified connection (0.8 g, 69%) was obtained as a white solid from methyl ester (±)3-[6-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]naphthyl]-2-ethoxypropanol acid (1.2 g, of 2.66 mmol)obtained in example 12, by the method similar to that described in example 26. TPL 102-104°C.

1H-NMR (CDCl3, 200 MHz): δ to 1.15 (t, J=7.01 Hz, 3H), 3,06 (t, J=4,98 Hz, 2H), is 3.08-3,63 (complex, 4H), of 3.77-3,83 (complex, 4H), to 4.15 (dd, J=4,15 and 4,18 Hz, 1H), 4,28 (t, J=5,95 Hz, 2H), 6,59-6,79 (comp is CEN, 2N), of 6.96 and 7.36 (complex, 5H), to 7.61-7,79 (complex, 3H), COOH proton is not detected due to the broadening of the peak.

EXAMPLE 44

(±)3-[6-[2-(2,3-Dihydro-1,4-benzothiazin-4-yl)ethoxy]naphthyl]-2-ethoxypropanol acid, sodium salt

The specified connection (0.16 g, 76%) was obtained as a white solid from (±)3-[6-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]naphthyl]-2-ethoxypropanol acid (0.2 g, 0,457 mmol)obtained in example 43, by the method similar to that described in example 27. TPL 138-140°C.

1H-NMR (CDCl3, 200 MHz): δ and 0.98 (t, J=7,06 Hz, 3H), 2,72-2,90 (complex, 1H), 2,92-3,21 (complex, 3H), 3,32-3,54 (complex, 2H), 3,61-3,91 (complex, 5H), 4,28 (bs, 2H), 6,56 (d, J=7,00 Hz, 1H), 6.73 x-7,00 (complex, 3H), 7,05-7,30 (complex, 2H), 7,38 (d, J=8,30 Hz, 1H), 7,60-7,82 (complex, 3H).

EXAMPLE 45

(±)3-[4-[2-(2,3-Dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-hydroxypropanoic acid

The specified connection (0.06 g, 43%) was obtained as a brown viscous liquid (±)ethyl-3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-hydroxypropanoate (0.15 g, 0.40 mmol)obtained in example 13 by the method similar to that described in example 26.

1H-NMR (CDCl3, 200 MHz): δ 2,85-3,19 (complex, 2H), 3.43 points (t, J=4,15 Hz, 2H), 3,61 (t, J=5,49 Hz, 2H), 4,07 (t, J=5,40 Hz, 2H), 4,16 (t, J=4,48 Hz, 2H), 4,45 (bs, 1H), 6,50-6,82 (complex, 6N), was 7.08 (t, J=7,88 Hz, 2H), COOH protons and HE's not op Adelaide due to the broadening of the peak.

EXAMPLE 46

(±)3-[4-[2-(2,3-Dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-hydroxypropanoic acid

The specified connection (0.7 g, 46%) was obtained as a white solid from ethyl ether (±) ethyl-3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-hydroxypropanoic acid (1.7 g, 4,39 mmol)obtained in example 14, by the method similar to that described in example 26. TPL 74-76°C.

1H-NMR (CDCl3, 200 MHz): δ 2,88-3,18 (complex, 4H), 3,69-3,79 (complex, 4H), to 4.15 (t, J=5,72 Hz, 2H), 4,45 (dd, J=6.73 x and 4,79 Hz, 1H), 4,51-equal to 4.97 (bs, exchanges with D2O, 1H), 6,65-6,89 (complex, 4H), 6,94-7,17 (complex, 4H), COOH proton is not detected due to the broadening of the peak.

EXAMPLE 47

(±)3-[4-[2-(2,3-Dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-benzyloxypropionic acid

The specified connection (0.15 g, 67%) was obtained as a thick liquid from ethyl ether (±)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-benzyloxypropionic acid (0.24 g, 0.52 mmol)obtained in example 15, by the method similar to that described in example 26.

1H-NMR (CDCl3, 200 MHz): δ 1,40 is 2.80 (br, 1H, exchanges with D2O), 2,99-3,18 (complex, 2H), 3,51 (t, J=4,34 Hz, 2H), 3,70 (t, J=of 5.82 Hz, 2H), 4,13-4,24 (complex, 5H), 4,51 (d, J=17,0 Hz, 2H), 6,60-6,89 (complex, 6N), 7,10-7,37 (complex, 7H).

EXAMPLE 48

(±)3-[4-[2-(2,3-Dihydro-1,4-benzoxazin-4-yl)is the si]phenyl]-2-benzyloxypropionic acid, sodium salt

The specified connection (0.1 g, 73%) was obtained in the form of hygroscopic substances cream color (±) 3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-benzyloxypropionic acid (of 0.13 g, 0.30 mmol)obtained in example 47, according to the method similar to that described in example 27.

1H-NMR (DMSO-d6, 200 MHz): δ 2,62-2,74 (complex, 1H), 2,89-2,98 (complex, 1H), 3,48 (t, J=4,20 Hz, 2H), to 3.67 (t, J=5,48 Hz, 2H), 4,12-4.26 deaths (complex, 5H)and 4.65 (d, J=12,45 Hz, 2H), 6,45-6,84 (complex, 6N), 7,12-of 7.25 (complex, 7H).

EXAMPLE 49

(±)3-[4-[2-(2,3-Dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-butoxypropan acid

The specified connection (0.25 g, 67%) was obtained as a viscous liquid of ethyl ether (±)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-butoxypropan acid (0.4 g, of 0.93 mmol)obtained in example 16, by the method similar to that described in example 26.

1H-NMR (CDCl3, 200 MHz): δ of 0.87 (t, J=7,15 Hz, 3H), 1,25-1,40 (complex, 2H), 1,49-1,66 (complex, 2H), 2.95 and-3,15 (complex, 2H), 3,43-3,53 (complex, 4H), 3,68 (t, J=5,49 Hz, 2H), 4,00-4,12 (complex, 1H), 4,14 (t, J=5,65 Hz, 2H), 4,22 (t, J=4,25 Hz, 2H), 6,60-6,89 (complex, 6N), 7,12 (d, J=8,39 Hz, 2H), COOH proton is not detected due to the broadening of the peak.

EXAMPLE 50

(±)3-[4-[2-(2,3-Dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-butoxypropan acid, sodium salt

The specified connection (0.12 g, 57%) was obtained in the form of hygroscopic substances cream color (±)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-butoxypropan acid (0.2 g, 0.5 mmol)obtained in example 49, by the method similar to that described in example 27.

1H-NMR (DMSO-d6, 200 MHz): δ 0,78 (t, J=7,06 Hz, 3H), 1,16-1,56 (complex, 4H), 2,52-2,64 (complex, 1H), 2,79-2,87 (complex, 1H), 2,99-3,18 (complex, 2H), 3,40 (bs, 2H), 3,66 (t, J=5,31 Hz, 2H), 4,10-4,25 (complex, 5H), 6,52-of 6.90 (complex, 6N), 7,12 (d, J=8,30 Hz, 2H).

EXAMPLE 51

(±)3-[4-[2-(2,3-Dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-hexyloxyphenol acid

The specified connection (0.17 g, 60%) was obtained as a greenish liquid from ethyl ether (±)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-hexyloxyphenol acid (0.3 g, of 0.65 mmol)obtained in example 17, by the method similar to that described in example 26.

1H-NMR (CDCl3, 200 MHz): δ 0,86 (t, J=5,72 Hz, 3H), 1,25-1,33 (complex, 4H), 1.41 to 1,75 (complex, 4H), 2,94-3,06 (complex, 2H), 3,36-to 3.58 (complex, 4H), 3,68 (t, J=5,49 Hz, 2H), 4,01-4,06 (complex, 1H), 4,14 (t, J=5,70 Hz, 2H), 4,22 (t, J=4,15 Hz, 2H), of 6.71-7,08 (complex, 6N), 7,12 (d, J=8,40 Hz, 2H), COOH proton is not detected due to the broadening of the peak.

EXAMPLE 52

(±)3-[4-[2-(2,3-Dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-hexyloxyphenol acid, sodium salt

The specified connection (0.1 g, 52%) was obtained as a white hygroscopic substances from (±)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-hexyloxyphenol acid (0.18 g, 0.42 mmol)obtained in example 51, according to the method similar to that described in example 27.

1H-NMR (DMSO-d6, 200 MHz): δ of 0.82 (t, J=5,72 Hz, 3H), 1,10-1,45 (complex, 8H), 2,75-2,96 (complex, 2H), 3,35-3,56 (complex, 4H), to 3.67 (t, J=and 5.30 Hz, 2H), 4,08-4,21 (complex, 5H), 6,50-6,82 (complex, 6N), 7,12 (d, J=8,00 Hz, 2H).

EXAMPLE 53

(±)3-[4-[2-(2,3-Dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-phenoxypropanol acid

The specified connection (0.1 g, 53%) was obtained as a colourless liquid of methyl ester (±)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-phenoxypropanol acid (0.2 g, 0,461 mmol)obtained in example 19, by the method similar to that described in example 26.

1H-NMR (CDCl3, 200 MHz): δ 2,40 is 2.80 (bs, 1H, exchanges with D2O), up 3.22 (d, J=5,80 Hz, 2H), 3,49 (t, J=4,25 Hz, 2H), to 3.67 (t, J=of 5.81 Hz, 2H), 4,14 (t, J=of 5.81 Hz, 2H), 4,21 (t, J=4,16 Hz, 2H), 4,82 (t, J=5,90 Hz, 1H), 6,61-7,02 (complex, 8H), 7,17-7,30 (complex, 5H).

EXAMPLE 54

(±)3-[4-[2-(2,3-Dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-phenoxypropanol acid

The specified connection (0.2 g, 51%) was obtained in the form of a resinous liquid of methyl ester (±)3-[4-[2-(2,3-dihydro-1,4-benzodia the Jn-4-yl)ethoxy]phenyl]-2-phenoxypropanol acid (0.4 g, 0.9 mmol)obtained in example 21, by the method similar to that described in example 26.

1H-NMR (CDCl3, 200 MHz): δ to 3.02 (t, J=5,00 Hz, 2H), up 3.22 (d, J=6.25 Hz, 2H), 3,68-3,78 (complex, 4H), 4,14 (t, J=of 5.81 Hz, 2H), 4,50 (t, J=to 6.19 Hz, 1H), 4,90-of 5.40 (b, 1H, exchanges with D2O)6,58-6,86 (complex, 7H), 6,94-7,07 (complex, 2H), 7.18 in-7,29 (complex, 4H).

EXAMPLE 55

(±)3-[4-[2-(2,3-Dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-phenoxypropanol acid, sodium salt

The specified connection (0.05 g, 48%) was obtained in the form of a hygroscopic substance of (±)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-phenoxypropanol acid (0.1 g, 0.24 mmol)obtained in example 53, by the method similar to that described in example 27.

1H-NMR (DMSO-d6, 200 MHz): δ 2,81-3,09 (complex, 2H), 3,42 (bs, 2H), 3,65 (t, J=4.5 Hz, 2H), 4,12 (bs, 4H), 4,22-4,32 (complex, 1H), 6,50-6,92 (complex, 8H), 7,10-7,33 (complex, 5H).

EXAMPLE 56

(±)2-Methyl-3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-phenoxypropanol acid, methyl ester

The specified connection (0.27 g, 87%) was obtained as a viscous liquid of methyl ester (±)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-phenoxypropanol acid (0.3 g, 0.69 mmol)obtained in example 19, by the method similar to that described in example 7.

1H-NMR (CDCl3, 200 MHz): δ 1,9 (s, 3H), 3,09 and 3.26 (1H, 2d, J=13,7 Hz each), 3,51 (t, J=4,30 Hz, 2H), 3,66-to 3.73 (complex, 5H), is 4.15 (t, J=5.50 Hz, 2H), 4,22 (t, J=4,24 Hz, 2H), 6,61-7,01 (complex N), 7,12-7,22 (complex, 4H).

EXAMPLE 57

(±)2-Methyl-3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-phenoxypropanol acid

The specified connection is made (0.13 g, 50%) was obtained as a pale yellow hygroscopic substance of the methyl ester (±)2-methyl-3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-phenoxypropanol acid (0.27 g, of 0.60 mmol)obtained in example 56, according to the method similar to that described in example 26.

1H-NMR (CDCl3, 200 MHz): δ of 1.42 (s, 3H), 3,12 and 3,29 (1H, 2d, J=14.1 Hz each), 3,50 (t, J=4,50 Hz, 2H), 3,69 (t, J=ceiling of 5.60 Hz, 2H), 4,16 (t, J=of 5.81 Hz, 2H), 4,22 (t, J=4,50 Hz, 2H), 6,62-7,17 (complex N), 7,21-7,30 (complex, 4H), proton COOH is not defined due to the broadening of the peak.

EXAMPLE 58

(±)2-Methyl-3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-phenoxypropanol acid, sodium salt

The specified connection (to 0.055 g, 46%) was obtained in the form of a hygroscopic pale yellow powder (±)2-methyl-3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-phenoxypropanol acid (of 0.13 g, 0.28 mmol)obtained in example 57, according to the method similar to that described in example 27.

1H-NMR (CDCl3, 200 MHz): δ to 1.15 (s, 3H), 2,92-3,21 (complex, 2H), 3,47 (s, 2H), to 3.67 (bs, 2H), 4,14 (bs, 4H), 6,53-of 6.90 (complex, N), 7,08-7,30 (complex, 4H).

EXAMPLE 59

(±)2-Methyl-3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-phenoxypropanol acid, methyl ester

The specified connection (0.96 g, 93%) was obtained as a pale yellow liquid of methyl ester (±)3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-phenoxypropanol acid (1.0 g, 2.22 mmol)obtained in example 21, by the method similar to that described in example 7.

1H-NMR (CDCl3, 200 MHz): δ of 1.40 (s, 3H), 3,03 (t, J=4,90 Hz, 2H), 3,09 3.27 (1H, 2d, J=13,7 Hz each), 3,70-3,85 (complex, 7H), to 4.16 (t, J=of 5.81 Hz, 2H), 6,60-6,89 (complex, 6N), of 6.96-7,30 (complex, 7H).

EXAMPLE 60

(±)2-Methyl-3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-phenoxypropanol acid

The specified connection (0.6 g, 65%) was obtained as a viscous liquid of methyl ester (±)2-methyl-3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-phenoxypropanol acid (0.96 g, 2.00 mmol)obtained in example 59, according to the method similar to that described in example 26.

1H-NMR (CDCl3, 200 MHz): δ of 1.42 (s, 3H), 3,03 (t, J=5,00 Hz, 2H), 3,12 and 3.30 (1H, 2d, J=13,8 Hz each), 3,70-3,80 (complex, 4H), to 4.15 (t, J=5.50 Hz, 2H), 6,58-7,08 (complex, 8H), 7.18 in-7,30 (complex, 5H), COOH proton is not detected due to the broadening of the peak.

EXAMPLE 61

(±)3-[4-[2-(23-Dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid, 4-nitrophenyloctyl ether

The specified connection (0.15 g, 38%) was obtained as a yellow liquid (±)3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid (0.3 g, 0.77 mmol)obtained in example 29, and 4-NITROPHENOL by method similar to that described in example 32.

1H-NMR (CDCl3, 200 MHz): δ to 1.24 (t, J=6,92 Hz, 3H), 3.04 from (t, J=5,16 Hz, 2H), 3,12 (d, J=6,63 Hz, 2H), 3.46 in-the 3.65 (complex, 1H), 3,70-3,86 (complex, 5H), to 4.16 (t, J=5,23 Hz, 2H), 4.26 deaths (t, J=5.50 Hz, 1H), 6,62-6,74 (complex, 2H), at 6.84 (d, J=8,62 Hz, 2H), 6,94-7,22 (complex, 6N), 8,23 (d, J=9,00 Hz, 2H).

EXAMPLE 62

(±)3-[4-(4-Benzyl-3,4-dihydro-1,4-benzoxazin-2-yl)methoxyphenyl]-2-ethoxypropanol acid

The specified connection (0.4 g, 57%) was obtained as a viscous liquid of methyl ester (±)3-[4-(4-benzyl-3,4-dihydro-1,4-benzoxazin-2-yl)methoxyphenyl]-2-ethoxypropanol acid (0.8 g, of 2.16 mmol)obtained in example 25, by the method similar to that described in example 26.

1H-NMR (CDCl3, 200 MHz): δ of 1.17 (t, J=7,00 Hz, 3H), 2,99-3,13 (complex, 2H), 3,31-the 3.65 (complex, 4H), 4,01-4,24 (complex, 3H), of 4.45 (d, J=3,40 Hz, 2H), to 4.52-4,59 (complex, 1H), 6,62 of 6.68 (complex, 6N), 7,14 (d, J=at 8.60 Hz, 2H), 7,27 (s, 5H), COOH proton is not is determined from the broadening of the peak.

EXAMPLE 63

(±)3-[4-(4-Benzyl-3,4-dihydro-1,4-benzoxazin-2-yl)methoxyphenyl]-2-ethoxypropanol acid, sodium salt

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The specified connection (0.15 g, 75%) was obtained as a colourless hygroscopic substances from (±)3-[4-(4-benzyl-3,4-dihydro-1,4-benzoxazin-2-yl)methoxyphenyl]-2-ethoxypropanol acid (0.2 g, 0.44 mmol)obtained in example 62, according to the method similar to that described in example 27.

1H-NMR (DMSO-d6, 200 MHz): δ 0,99 (t, J=6,97 Hz, 3H), 2,60-2,90 (complex, 2H), 3,30-the 3.65 (complex, 5H), 4,16 (d, J=5,00 Hz, 2H), 4,40-4,65 (complex, 3H), 6,55-6,89 (complex, 6N), 7,14 (d, J=8,50 Hz, 2H), 7,32 (s, 5H).

EXAMPLE 64

(±)3-[4-(4-Benzyl-3,4-dihydro-1,4-benzoxazin-2-yl)methoxyphenyl]-2-ethoxypropanol acid, 4-nitrophenyloctyl ether

The specified connection (0.6 g, 100%) was obtained as a dark brown liquid of (±)3-[4-(4-benzyl-3,4-dihydro-1,4-benzoxazin-4-yl)methoxyphenyl]-2-ethoxypropanol acid (0.5 g, of 1.34 mmol)obtained in example 62, and 4-NITROPHENOL by method similar to that described in example 32.

1H-NMR (CDCl3, 200 MHz): δ 1,25 (t, J=7,00 Hz, 3H), 3,14 (d, J=6,60 Hz, 2H), 3.33 and-3,55 (complex, 3H), 3,69-of 3.77 (complex, 1H), 4,05-or 4.31 (complex, 3H), 4,46 (d, J=3,40 Hz, 2H), 4,55-br4.61 (complex, 1H), 6,63 of 6.68 (complex, 6N), 7,11-7,28 (complex, 7H), 7,52 (d, J=7,60 Hz, 2H), 8,23 (d, J=9,00 Hz, 2H).

EXAMPLE 65

(-)2-Ethoxy-3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]propanoic acid, ethyl ester

Ethyl ester of ()2-ethoxy-3-(4-hydroxyphenyl)propanoic acid (0.5 g, 2.1 mmol) was dissolved in anhydrous N,N-dimethylformamide (0.8 ml) and with stirring was added anhydrous potassium carbonate (of 1.16 g, 8.4 mmol), stirred 20 minutes at about 25°and added mesilate 2,3-dihydro-1,4-benzothiazin-1-ethanol (or 0.57 g, 2.1 mmol) in 4 ml of anhydrous DMF. The reaction mixture was stirred at about 60°C for 18 hours, cooled to 25°and filtered. The filtrate was diluted with ethyl acetate (100 ml) and washed with water (3×100 ml), dried over anhydrous Na2SO4and evaporated.

The compound was purified by chromatography on silica gel using 10% ethyl acetate in petroleum ether as eluent, obtaining mentioned in the title compound as a light brown oil (0,63 g, 70%). [α]25D=is 12.5° (C=1,0, CHCl3).

1H-NMR (CDCl3, 200 MHz): δ 1,10-1,30 (m, 6H), to 2.94 (d, J=6.42 per Hz, 2H), 3,01-3,10 (m, 2H), 3,28-3,68 (m, 2H), 3,70-of 3.80 (m, 4H), of 3.95 (t, J=6.42 per Hz, 1H), 4,10-4,22 (m, 4H), 6,55-6,74 (m, 2H), 6,80 (d, J=8,63 Hz, 2H), 6,98-7,10 (m, 2H), 7,14 (d, J=8,63 Hz, 2H).

EXAMPLE 66

(+)2-Ethoxy-3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]propanoic acid, ethyl ester

The specified connection (0.9 g, 76%) was obtained as a light brown oil from ethyl ether (+)2-ethoxy-3-(4-hydroxyphenyl)propanoic acid (0.68 g, 2.8 mmol), nelfinavir 2,3-dihydro-1,4-benzothiazin-1-ethanol (0,78 g, 2.8 mmol) and anhydrous K2CO3(1,57 g, 113 mmol) according to the method similar to that described in example 65. [α]25D=10,8° (C=1,05, CHCl3).

1H-NMR (CDCl3, 200 MHz): δ 1,10-1,30 (m, 6H), of 2.93 (d, J=6,55 Hz, 2H), 3.00 and-of 3.07 (m, 2H), 3.25 to 3,68 (m, 2H), 3,69-of 3.80 (m, 4H), of 3.96 (t, J=6,55 Hz, 1H), 4,10-4,20 (m, 4H), 6,55 to 6.75 (m, 2H), 6,80 (d, J=8,30 Hz, 2H), 6.98-7,10 (m, 2H), 7,14 (d, J=8,30 Hz, 2H).

EXAMPLE 67

(-)2-Ethoxy-3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]propanoic acid

Ethyl ester of (-)2-ethoxy-3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]propanoic acid (0,050 g, 0.12 mmol)obtained in example 65 was dissolved in methanol and stirring was added a solution of NaOH (0,050 g in 1 ml water) at 26°for hydrolysis of the ester. After 20 minutes, the methanol was evaporated under reduced pressure and a temperature below 30°C (water bath)and the residue was immediately diluted with ice water (5 ml) and cooled to approximately 3°C (on ice). The contents were acidified to pH 7.0 with 0,5N HCl, thoroughly washed with 0.3% ethyl acetate in diethyl ether (3×10 ml) and was extracted with ethyl acetate (3×10 ml). The extracts were washed with water and saturated NaCl solution, dried over anhydrous Na2SO4and evaporated the solvent under reduced pressure and a temperature below 30°getting mentioned in the title compound as a colorless sticky mass (0.037 g, 80%). [α]20D=-15,8° (C=1,050, Meon).

1H-NMR (CDCl3/sub> , 200 MHz): δ of 1.17 (t, J=7.01 Hz, 3H), 2,88 is 3.15 (m, 4H), 3,32-3,68 (m, 2H), 3,70-of 3.80 (m, 4H), 4,00-4,10 (m, 1H), 4,15 (t, J=of 5.81 Hz, 2H), 6,53-of 6.78 (m, 2H), for 6.81 (d, J=8,63 Hz, 2H), 6,95-7,10 (m, 2H), 7,15 (d, J=8,63 Hz, 2H).

EXAMPLE 68

(+)2-Ethoxy-3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]propanoic acid

The specified connection (0.07 g, 78%) was obtained as off-white sticky mass of ethyl ester of (+)2-ethoxy-3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]propanoic acid (0.1 g, 0.24 mmol)obtained in example 66, and a solution of NaOH (0.1 g, 2.4 mmol) by the method similar to that described in example 67.

1H-NMR (CDCl3, 200 MHz): δ to 1.15 (t, J=6,98 Hz, 3H), 2,87-3,14 (m, 4H), 3,30-3,70 (m, 2H), 3.72 points-is 3.82 (m, 4H), 4,00-4,12 (m, 1H), 4,12 (t, J=5,78 Hz, 2H), 6,55-6,70 (m, 2H), for 6.81 (d, J=8,62 Hz, 2H), 6.87 in-7,10 (m, 2H), 7,14 (d, J=8,62 Hz, 2H).

EXAMPLE 69

(±)3-[4-[2-(2,3-Dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid, magnesium salt

(±)3-[4-[2-(2,3-Dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid (100 mg, 0,258 mmol)obtained in example 29 was dissolved in methanol (5 ml)was added magnesium hydroxide (7.5 mg, 0,129 mmol) and stirred the reaction mixture at 30°within 24 hours, the solvent was evaporated and the residue is washed with anhydrous diethyl ether, removing the unreacted starting material. The white powder was dried at 50°C under vacuum during the 7 hours getting listed in the title compound as a white powder (90 mg, 88%). TPL 158°C-160°C.

1H-NMR (d4-MeOH): δ of 1.09 (t, J=7,00 Hz, 3H), 2,78 (dd, J=8,40 and 14.0 Hz, 1H), 2,90 was 3.05 (m, 3H), 3,15-to 3.67 (m, 2H), 3,69-to 3.73 (m, 4H), 3.75 to 3,90 (m, 1H), 4,14 (t, J=5,40 Hz, 2H), 6,55 (d, J=7,50 Hz, 1H), 6,70-PC 6.82 (m, 3H), of 6.90 (d, J=7,50 Hz, 2H), 7,16 (d, J=8,40 Hz, 2H).

EXAMPLE 70

(-)3-[4-[2-(2,3-Dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid, sodium salt

A mixture of (-)3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid (0.2 g, 0.51 mmol)obtained in example 67, and sodium methoxide (0,0279 g, 0.51 mmol) in methanol (4 ml) was stirred at room temperature for 2 hours. The methanol was removed under reduced pressure, and the residue was treated with ether (3×10 ml). The precipitation was filtered and dried over P2O5under vacuum, obtaining specified in the title compound in the form of hygroscopic solids (0,105 g, 50%).

1H-NMR (DMSO-d6): δ 0,92 is 0.99 (t, J=6,64 Hz, 3H), 2,50-2,77 (m, 3H), 3,02-3,10 (m, 3H), 3,44-3,50 (t, J=8,90 Hz, 1H), 3,55 at 3.69 (m, 4H), 4,11-4,13 (m, 2H), 6,53-to 6.57 (d, J=7,05 Hz, 1H), 6,77-PC 6.82 (d, J=8,30 Hz, 2H), 6.90 to-for 7.12 (m, 3H), 7,20-7,22 (d, J=4,75 Hz, 2H).

EXAMPLE 71

(-)3-[4-[2-(2,3-Dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid, magnesium salt

A mixture of (-)3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-etox the propanoic acid (0,320 g, 0.82 mmol)obtained in example 67, and magnesium hydroxide (0,024 g, 0.41 mmol) in methanol (12 ml) was boiled under reflux for 15 hours and cooled to room temperature. The methanol was removed under reduced pressure, and the residue was treated with petroleum ether, filtered and dried over P2O5getting listed in the title compound (0,250 g, 73%). TPL 275°C-285°C. [α]25D=-70,5° (C=1,0, CHCl3).

1H-NMR (CDCl3+CD3OD): δ 1,10 (t, J=7,06 Hz, 3H), 2,81-to 3.02 (m, 3H), 3.27 to and 3.31 (m, 2H), 3,55-with 3.79 (m, 5H), 3,81-3,86 (t, J=3,74 Hz, 1H), 4,12-4,17 (t, J=5,49 Hz, 2H), 6,00-is 6.54 (d, J=7,47 Hz, 1H), 6,79-PC 6.82 (d, J=7,56 Hz, 2H,), 6,90-6,94 (m, 3H), 7,14-7,19 (d, J=8,39 Hz, 2H).

EXAMPLE 72

(-)3-[4-[2-(2,3-Dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid, arginine salt

L-Arginine (0,072 g, 0.4 mmol) was dissolved in water (0,360 ml) and added into a solution of (-)3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid (0,180 g, 0.46 mmol)obtained in example 67, in ethanol (4 ml) at 50°C, cooled to room temperature and was stirred for 10 hours. The solvent was removed under reduced pressure and the residual water was removed azeotrope with toluene. The residue was dried under vacuum, obtaining specified in the header connection (0,175 g, 99.5%pure). TPL 115-125°C. [α]25D=-13,00° (C=1.0, the Meon).

1NAMR (CD 3OD): δ of 1.05 to 1.12 (t, J=of 6.96 Hz, 3H), 1,69-of 1.85 (m, 4H), 2,79-to 3.02 (m, 5H), 3,15-3,30 (m, 6N), 3,51-of 3.60 (q, J=6.73 x Hz, 2H), 3,62-3,81 (m, 6H), 4,12-4,18 (t, J=5,49 Hz, 2H), 6,54 return of 6.58 (t, J=7,38 Hz, 1H), 6,78-of 6.96 (m, 5H), 7,15-7,19 (d, J=8,21 Hz, 2H).

EXAMPLE 73

3-[4-[2-(2,3-Dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid, arginine salt

L-Arginine (0.152 g, 0.87 mmol) was dissolved in water (0.7 ml) and added into a solution of 3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid (0,360 g, 0.97 mmol)obtained in example 26, in ethanol (9 ml) at 50°C, cooled to room temperature and was stirred for 10 hours. The solvent was removed under reduced pressure and the residual water was removed azeotrope with toluene. The residue was dried under vacuum, obtaining mentioned in the title compound (0.3 g, 56%). TPL 180°S-190°C.

1H-NMR (CD3OD): δ 0,99 by 1.12 (t, J=6,92 Hz, 3H), 1,60 to 1.76 (m, 4H), to 2.75 (dd, J=10,0 and 5.4 Hz, 2H), 3,05-3,39 (m, 8H), 3,45-3,74 (m, 10H), of 4.05 (t, J=5,40 Hz, 3H), to 6.43-of 6.65 (m, 4H), 6,69 (d, J=8,62 Hz, 2H), 7,06 (d, J=to 8.62 Hz, 2H).

EXAMPLE 74

(-)2-Ethoxy-3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]propanoic acid, ethyl ester

In a mixture consisting of methanesulfonate 2,3-dihydro-1,4-benzoxazin-1-ethanol (27,0 g, 0.15 mmol), potassium carbonate (58,0 g, 0,420 mmol) and ethyl ether (-)2-ethoxy-3-(4-hydroxyphenyl)propanoic acid (25,0 g, 0,105 mmol), we use the and anhydrous N,N-dimethylformamide (800 ml) at 25° With and was heated at 60°C for 16 hours. Upon completion the reaction mixture was filtered, washed with DMF, diluted with water and extracted with ethyl acetate. The organic layer was thoroughly washed with water and saturated NaCl solution, dried over anhydrous Na2SO4and evaporated under reduced pressure. The crude product was purified by chromatography on silica gel using 5% ethyl acetate in petroleum ether as eluent, obtaining mentioned in the title compound as a brown liquid (18.2 g, 44%). [α]25D=-12,1° (C=1,0, CHCl3).

1H-NMR (CDCl3): δ 1,10-1,30 (m, 6H), 2.95 points (d, J=6,74 Hz, 2H), 3,20-of 3.60 (m, 4H), 3,66 (t, J=5,58 Hz, 2H), 3.96 points (t, J=6,74 Hz, 1H), 4,10-4,30 (m, 6H), PC 6.82 (d, J=8,63 Hz, 2H), 6,58-of 6.90 (m, 4H), to 7.15 (d, J=8,63 Hz, 2H).

EXAMPLE 75

(-)2-Ethoxy-3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]propanoic acid

Ethyl ester of (-)2-ethoxy-3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]propanoic acid (17.0 g, 0,0426 mmol)obtained in example 74 was dissolved in methanol (500 ml)was added 10% NaOH solution (135 ml) at 25°and was stirred for 30 minutes. The methanol was evaporated under reduced pressure and 20°C (water bath)and the residue was immediately diluted with ice water. The aqueous layer was washed with diethyl ether, acidified with 2N HCl and was extracted with ethyl acetate. The organic layer thoroughly flushing and water and a saturated solution of NaCl, dried over Na2SO4and evaporated the solvent under reduced pressure at 25°getting mentioned in the title compound as a thick light brown liquid (14.1 g, 89%). [α]25D=-18,3° (C=1.0, the Meon).

1H-NMR (CDCl3): δ of 1.17 (t, J=6,97 Hz, 3H), 2,95 (dd, J=5.99 and 14,11 Hz, 1H), is 3.08 (dd, J=4,24 and 14,11 Hz, 1H), 3,30-the 3.65 (m, 4H), of 3.69 (t, J=5,49 Hz, 2H), 4,00-4,10 (m, 1H), 4,12 (t, J=5,49 Hz, 2H), 4,20 (t, J=of 4.38 Hz, 2H), to 6.80 (d, J=8,40 Hz, 2H), 6,55-of 6.90 (m, 4H), to 7.15 (d, J=8,40 Hz, 2H).

EXAMPLE 76

(-)3-[4-[2-(2,3-Dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid, magnesium salt

(-)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid (14.0 g, 0,0377 mmol)obtained in example 75 was dissolved in anhydrous methanol (12 ml) was added magnesium hydroxide (1.10 g, 0,0188 mmol) under nitrogen atmosphere at 25°and then boiled under reflux for 18 hours. The solvent was evaporated under reduced pressure and the residue was carefully treated with anhydrous diethyl ether, and dried under a strong vacuum at 65°C (oil bath) for 30 minutes, getting mentioned in the title compound as a white solid (12.2 g, 83%). TPL 255°C-260°C. [α]25D=-22,3° (C=1.0, the Meon:CHCl3(1:1)).

1H-NMR (CDCl3+CD3OD): δ 0,99 (t, J=6,97 Hz, 3H), 2,70 (dd, J=8,40 and 4.12 Hz, 1H), 2,90 (dd, J=4,12 and 14,20Hz, 1H), 3,10-3,55 (m, 4H), of 3.57 (t, J=5,40 Hz, 2H), 3,70-of 3.80 (m, 1H), 4,00-4,10 (m, 4H), 6,70 (d, J=8,31 Hz, 2H), 6,35-to 6.80 (m, 4H), 7,07 (d, J=8,31 Hz, 2H).

EXAMPLE 77

(-)3-[4-[2-(2,3-Dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid, arginine salt

L-Arginine (6,16 g, 0,0354 mmol) was dissolved in water (20 ml) and stirring was made in solution (-)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid (19.6 g, 0,0395 mmol)obtained in example 75, in ethanol (300 ml) at 50°C, cooled to room temperature and was stirred for 15 hours. The solvent was removed azeotrope with toluene and the residue was treated with anhydrous diethyl ether, filtered and dried under vacuum over CaCl2during the night, getting mentioned in the title compound as a white powder (16.2 g, 76%). TPL 184-186°C. [α]25D=-23,4° (C=1.0, the Meon).

1H-NMR (CD3OD): δ 0,99 (t, J=7,06 Hz, 3H), 1,50-of 1.85 (m, 4H), 2,68 (dd, J=8,54 and 14,22 Hz, 1H), 2,80 (dd, J=4,35 and 14,22 Hz, 1H), 3,00-3,20 (m, 3H), 3.25 to of 3.48 (m, 4H), of 3.56 (t, J=5,39 Hz, 2H), 3,70 (dd, J=4,24 and 8,39 Hz, 1H), 4,06 (m, 4H), of 6.66 (d, J=8.53 Hz, 2H), 6.75 in to 6.35 (m, 4H), 7,06 (d, J=8.53 Hz, 2H).

Compounds of the present invention reduced the level of blood sugar, triglycerides, total cholesterol, LDL, lonp and increased HDL. It was shown in animal experiments both in vitro and in vivo.

Evidence of the effectiveness of connections

A) In vitro

a) Definition is the activity hPPARα

The ligand-binding domain hPPARα sewn to the DNA-binding domain of the yeast transcription factor GAL4 in a eukaryotic expression vector. Using as reagent for transfection drug Superfect (Qiagen, Germany), this plasmid was transferrable cells SOME 293 together with a reporter plasmid carrying the gene luciferase under the control GL4-specific promoter. After 42 hours after transfection) was added compound in various concentrations and allowed to incubated overnight. Luciferase activity as an indicator of binding compounds with PPARα/activation connection PPARα measured using the Luclite kit Packard company (USA) in the Top Count (Ivan Sadowski, Brendan Bell, Peter Broag and Melvyn Hollis. Gene. 1992. 118: 137-141; Superfect Transfection Reagent Handbook. February 1997. Qiagen, Germany).

b) determining the activity of hPPARγ

The ligand-binding domain hPPARγ1 sewn to the DNA-binding domain of the yeast transcription factor GAL4 in a eukaryotic expression vector. Using as reagent for transfection drug Lipofectamine (Gibco BRL, USA), this plasmid was transferrable cells SOME 293 together with a reporter plasmid carrying the gene luciferase under the control of GAL4-specific promoter. 48 hours after transfection) was added compound in a concentration of 1 μm and left to incubated overnight. Luciferase activity as an indicator of light is ivania compounds with PPARγ 1/activate connection PPARγ1 was measured using the Luclite kit (Packard, USA) in the Top Count, Packard company (Ivan Sadowski, Brendan Bell, Peter Broag and Melvyn Hollis. Gene. 1992. 118: 137-141; Guide to Eukaryotic Transfections with Cationic Lipid Reagents. Life Technologies, Gibco BRL, USA).

C) determination of the inhibition of HMG:CoA reductase activity

Containing reductase liver microsomes were isolated from rats fed food with the addition of 2% cholestyramine, in the middle of the dark cycle. Spectrophotometric determination was carried out in 100 mm KN2RHO4, 4 mm DTT, 0.2 mm NADPH, 0.3 mm HMG-CoA and 125 μg of enzyme liver microsomes. The total volume of the reaction mixture was 1 ml Reactions were initiated by addition of HMG-CoA. The reaction was carried out at 37°C for 30 minutes, noting the decrease in absorption at 340 nm. Blank solution contained the reaction mixture without substrate (Goldstein J.L. and Brown, M.S. Progress in understanding the LDL receptor and HMG CoA reductase, two membrane proteins that regulate the plasma cholesterol. J.Lipid Res. 1984, 25: 1450-1461). The compounds inhibited the enzyme HMG:CoA reductase.

B) In vivo

(a) the Effectiveness of the genetic models

Mutations in colonies of laboratory animals and differences in sensitivity to food regimes made possible the development of animal models independent from insulin diabetes, and hyperlipidemia, which are accompanied by obesity and insulin resistance. Such genetic models, as the mice db/db and ob/ob (Diabetes, (1982) 31(1): 1-6) and rats Zucer fa/fa, have been developed in various laboratories for understanding the pathophysiology of the disease and test the effectiveness of new compounds against diabetes, (1983) 32: 830-838; Annu. Rep. Sankyo Res. Lab. (1994) 46: 1-57). Homozygous mouse line S BL/KsJ-db/db developed in the USA by a firm Jackson Laboratory, suffer from obesity, hyperglycemia and are resistant to insulin (J. Clin. Invest., (1990) 85: 962-967), whereas heterozygous mice thin and normoglycemic. In the model db/db mice with age gradually develops insulinopenia that usually occurs to people in the later stages of type II diabetes when the blood sugar levels difficult to control. The condition of the pancreas and its changes vary susisiekti from the model. Since this model is similar to diabetes type II, it felt compounds of the present invention for the reduction of blood sugar and triglycerides in the blood.

In the experiments used male mice S BL/KsJ-db/db in age from 8 to 14 weeks weighing from 35 to 60 g, which were bred in the kennel Dr. Reddy's Research Foundation (DRF). Mice received standard feed (National Institute of Nutrition (NIN), Hyderabad, India) and acidified water ad libitum. For testing used animals with a blood sugar level of more than 350 mg/DL. Each group consisted of 4 mice.

The compounds suspended in a 0.25%solution of carboxymethylcellulose and introduced experimental group the e in doses from 0.1 to 30 mg/kg in the mouth by gavage daily for 6 days. The control group was administered the vehicle (10 ml/kg). On the 6th day took blood samples after 1 hour after administration of the compounds or media to assess biological activity.

Blood samples (100 µl) for measuring sugar levels and triglycerides were collected in tubes containing EDTA, through the orbital sinus using reparenting capillary, and then centrifuged to obtain plasma. The levels of glucose and triglycerides in plasma were measured spectrophotometrically using sets containing the enzymes glucose oxidase and glycerol-3-PO4oxidase/peroxidase, respectively (Dr. Reddy's Lab. Diagnostic Division Kits, Hyderabad, India).

Reducing sugar levels and triglycerides in the blood of the investigated compounds considered in the formula.

When testing was not observed side effects from these compounds of the present invention.

ConnectionDose (mg/kg)Reducing the level of glucose in the blood (%)Reduction of triglycerides (%)
Example 4135327
Example 5034523
Example 64104774

Line mouse ob/ob were obtained at 5 weeks of age from the fir is s Bomholtgard (Denmark) and were used at the age of 8 weeks. Rats with obesity lines Zucker fa/fa were obtained from the company IffaCredo (France) at 10 weeks of age and were used at the age of 13 weeks. Animals were kept on a 12-hour cycle of day/night at 25±1°C. Animals were given standard laboratory feed (NIN, Hyderabad, India) and water ad libitum (Fujiwara T., Yoshioka, S., Yoshioka T., Ushiyama J. and Horikoshi H. Characterization of new oral antidiabetic agent CS-045. Studies in KK and ob/ob mice and Zucker fatty rats. Diabetes. 1988. 37: 1549-1559).

The compounds were administered in doses of from 0.1 to 30 mg/kg/day for 6 days. Control animals were injected media (0,25%solution of carboxymethyl cellulose, 10 ml/kg) into the mouth by gavage.

Blood samples were taken in the fed state after 1 hour after administration of the compounds on the 0-th and 9-th day. Blood was collected in tubes containing EDTA, retroorbital sinus using reparenting capillary. After centrifugation was collected plasma samples for analysis of triglycerides, glucose, free fatty acid, total cholesterol and insulin. Triglycerides, glucose, total cholesterol were measured using commercial kits (Dr. Reddy's Laboratory, Diagnostic Division, Hyderabad, India). The level of free fatty acids were measured using a commercial kit company Boehringer (Germany). Insulin levels were measured using RIA kit company BARC (India). The degree of impact of various parameters during the tests considered in the formula below

In mice ob/ob conducted a test of glucose tolerance after 9 days of taking the drugs. Mice were kept hungry for 5 hours, and then were injected glucose in a dose of 3 g/kg orally. After 0, 15, 30, 60 and 120 minutes took blood samples for determination of glucose level.

Obtained in mice db/db and ob/ob rats and Zucker fa/fa results show that the new compounds of the present invention have therapeutic potential as tools for the prevention or treatment of diabetes, obesity, cardiovascular disorders such as hypertension, hyperlipidemia and other diseases, as it is known from literature that these diseases are linked to each other.

The levels of glucose and triglycerides in the blood also decreased at doses more than 10 mg/kg Usually the degree of reduction depends on the dose and reaches a plateau at a certain dose.

b) Reduction of triglycerides and cholesterol in the blood on models of hypercholesterolemia in rats

Male rats Sprague Dawley (rock NIN) were bred in the kennel DRF. Animals were kept on a 12-hour cycle of day/night at 25±1°C. In the experiments used rats weighing 180-200 g Hypercholesterolemia in animals caused by the addition of 2% cholesterol and 1% cholate sodium in standard laboratory feed (National Institute of Nutrition (NIN), Hyderabad, India) for 6 days. Throughout the experiments, animals were kept n the same diet (Petit D., Bonnefis M.T., Rey C. Infante and R.Effects of ciprofibrate on liver lipids and lipoprotein synthesis in normo - and hyperlipidemic rats. Atherosclerosis. 1988. 74: 215-225).

The compounds were administered orally in doses of from 0.1 to 30 mg/kg/day for 3 days. The control group was injected only media (0,25%solution of carboxymethyl cellulose, 10 ml/kg).

Blood samples were taken in the fed state after 1 hour after administration of the compounds on the 0-th and 3-th day. Blood was collected in tubes containing EDTA, retroorbital sinus using reparenting capillary. After centrifugation was collected plasma samples for analysis of total cholesterol, HDL and triglycerides. Triglycerides, total cholesterol and HDL cholesterol were determined using commercial kits (Dr.Reddy's Laboratory, Diagnostic Division, India). Cholesterol LDL and lonp account of the results of determination of total cholesterol, HDL and triglycerides. The degree of impact of various parameters during the tests considered in the formula.

ExampleDose (mg/kg)Triglycerides (%)↓Total cholesterol (%) ↓HDL (%) ↑LDL (%) ↑LEP (%) ↓
Example 2714357375879
Example 44150 42464453
↓ - drop, ↑ - increase

C) Reduction of triglycerides and total cholesterol in the blood in mice Swiss albino and Guinea pigs

Male mice of Swiss albino (SAM) and male Guinea pigs were obtained from NIN and was kept in the nursery DRF. All these animals were kept on a 12-hour cycle of day/night at 25±1°C. Animals were given standard laboratory feed (NIN, Hyderabad, India) and water ad libitum. Used SAM weighing 20-25 g and Guinea pigs weighing 500-700 g (Oliver P., PIancke M.O., Marzin D., Clavey V., Sauzieres J. and Fruchart J.C. Effects of fenofibrate, gemfibrozil and nicotinic acid on plasma lipoprotein levels in normal and hyperlipidemic mice. Atherosclerosis. 1988. 70: 107-114).

The investigated compounds were administered to mice Swiss albino orally in doses of 0.3 to 30 mg/kg/day for 6 days. Control mice were injected media (0,25%solution of carboxymethyl cellulose, 10 ml/kg). Guinea pigs tested compound was administered orally in doses of 0.3 to 30 mg/kg/day for 6 days. Control animals were injected media (0,25%solution of carboxymethyl cellulose, 5 ml/kg).

Blood samples were taken in the fed state after 1 hour after administration of the compounds on the 0-th and 6-th day. Blood was collected in tubes containing EDTA, retroorbital sinus using reparenting capillary. After centrifugation was collected about azzy plasma for the analysis of triglycerides and total cholesterol (Wieland O. Methods of Enzymatic Analysis. Bergmeyer N.O., Ed., 1963. 211-214; Trinder P. Ann. Clin. Biochem. 1969. 6: 24-27). Triglycerides, total cholesterol and HDL cholesterol were determined using commercial kits (Dr. Reddy's Diagnostic Division, Hyderabad, India).

ConnectionDose (mg/kg)Reduction of triglycerides (%)
Example 33355
Example 411054
Example 43349
Example 63357

C) Reduction of body weight in hamsters fed cholesterol

Male Syrian hamsters were obtained from NIN (Hyderabad, India). Animals were kept in the nursery DRF on a 12-hour cycle of day/night at 25±1°and they had free access to food and water. Animals received standard laboratory feed containing 1% cholesterol (NIN), starting from the first day of the experiment.

The compounds were administered orally in doses of from 1 to 30 mg/kg/day for 15 days. Animals of the control group were injected media (deionized water Mill Q., 10 ml/kg/day). Animals were weighed every 3 days.

ExampleDose (mg/kg/day)The decrease in body weight (%)
Example 27 1012
Example 301018

Formulas for calculations

1. The percentage of reducing sugar/triglycerides/total cholesterol in the blood is thought by the formula:

where OS is the value in the control group at day 0,

FROM the value in the experimental group at day 0,

TC - value in the control group on the day of analysis,

TT - value in the experimental group on the day of analysis.

2. The levels of LDL cholesterol and lonp considered by the formulas:

1. Substituted bicyclic heterocyclic compound of the formula (I)

its tautomeric forms, stereoisomers, polymorphic forms, pharmaceutically acceptable salt, pharmaceutically acceptable solvate, where the group R1, R2, R3, R4group and R5and R6when they are connected to carbon atoms, represent hydrogen, halogen, hydroxy, alkyl, alkoxy; R5and R6one, or both, can also be oxoprop when they are linked to the carbon atom; when R5and R6linked to the nitrogen atom, they represent a hydrogen, hydroxy or unsubstituted group selected from alkyl, alkoxy, aralkyl; x is the heteroatom, selected from to the of Sloboda or sulfur; Ar denotes unsubstituted divalent phenylene, naftilan or benzofuran; R7means a hydrogen atom, alkoxy, lower alkyl or forms a bond with a neighboring group, R8; R8means hydrogen, lower alkyl, unsubstituted or substituted aralkyl, or forms a bond with R7; R9means hydrogen or unsubstituted group selected from alkyl, aryl; R10means hydrogen or unsubstituted group selected from alkyl, aryl; Y represents oxygen or NR12where R12means hydrogen, alkyl; n is an integer from 1 to 4; m is an integer 1.

2. The method of obtaining the compounds of formula (I)

its tautomeric forms, stereoisomers, polymorphic forms, pharmaceutically acceptable salts, pharmaceutically acceptable solvate, where the group R1, R2, R3, R4group and R5and R6when they are connected to carbon atoms, represent hydrogen, halogen, hydroxy, alkyl, alkoxy; R5and R6one, or both, can also be oxoprop when they are linked to the carbon atom; when R5and R6linked to the nitrogen atom, they represent a hydrogen, hydroxy or unsubstituted group selected from alkyl, alkoxy, aralkyl; x is the heteroatom selected from oxygen or sulfur; Ar denotes unsubstituted dohale the fair phenylene, naftilan or benzofuran; R7forms a link with a neighboring group, R8; R9means hydrogen or unsubstituted group selected from alkyl, aryl; R10means hydrogen or unsubstituted group selected from alkyl, aryl; Y represents oxygen; n is an integer from 1 to 4; m is an integer 1, comprising the reaction of compounds of formula (IIIa)

where R1, R2, R3, R4, R5, R6, Ar, X, n and m have the above meanings, with a compound of formula (IIIb)

where R9and R10are defined above; R14means (C1-C6)alkyl; obtaining videopreteen the compounds of formula (I), and, optionally, converting the compounds of formula (I) into a pharmaceutically acceptable salt or pharmaceutically acceptable MES.

3. The method of obtaining the compounds of formula (I)

its tautomeric forms, stereoisomers, polymorphic forms, pharmaceutically acceptable salts, pharmaceutically acceptable solvate, where the group R1, R2, R3, R4group and R5and R6when they are connected to carbon atoms, represent hydrogen, halogen, hydroxy, alkyl, alkoxy; R5and R6one or both may also be present with the Oh oxoprop, when they are linked to the carbon atom; when R5and R6linked to the nitrogen atom, they represent a hydrogen, hydroxy or unsubstituted group selected from alkyl, alkoxy, aralkyl; x is the heteroatom selected from oxygen or sulfur; Ar denotes unsubstituted divalent phenylene, naftilan or benzofuran; R7forms a link with a neighboring group, R8; R9means hydrogen or unsubstituted group selected from alkyl, aryl; R10means hydrogen or unsubstituted group selected from alkyl, aryl; Y represents oxygen; n is an integer from 1 to 4; m is an integer 1, comprising the reaction of compounds of formula (IIIa)

where R1, R2, R3, R4, R5, R6, Ar, X, n and m have the above meanings, with a Wittig reagent with getting videopreteen the compounds of formula (I) and, optionally, converting the compounds of formula (I) into a pharmaceutically acceptable salt or pharmaceutically acceptable MES.

4. The method of obtaining the compounds of formula (I)

its tautomeric forms, stereoisomers, polymorphic forms, pharmaceutically acceptable salts, pharmaceutically acceptable solvate, where the group R1, R2, R3, R4group and R5and R6when they are associated with atom and carbon, represent hydrogen, halogen, hydroxy, alkyl, alkoxy; R5and R6one, or both, can also be oxoprop when they are linked to the carbon atom; when R5and R6linked to the nitrogen atom, they represent a hydrogen, hydroxy or unsubstituted group selected from alkyl, alkoxy, aralkyl; x is the heteroatom selected from oxygen or sulfur; Ar denotes unsubstituted divalent phenylene, naftilan or benzofuran; R7forms a link with a neighboring group, R8; R9means hydrogen or unsubstituted group selected from alkyl, aryl; R10means hydrogen or unsubstituted group selected from alkyl, aryl; Y represents oxygen; n is an integer from 1 to 4; m is an integer 1, comprising the reaction of compounds of formula (IIIh)

where R1, R2, R3, R4, R5, R6, X and p have the above meanings; L1means a leaving group with a compound of formula (IIIi)

where R7, R8, R9and R10have the above values; obtaining videopreteen the compounds of formula (I); and, optionally, converting the compounds of formula (I) into a pharmaceutically acceptable salt or pharmaceutically acceptable MES.

5. The method of obtaining connection is of formula (I)

its tautomeric forms, stereoisomers, polymorphic forms, pharmaceutically acceptable salts, pharmaceutically acceptable solvate, where the group R1, R2, R3, R4group and R5and R6when they are connected to carbon atoms, represent hydrogen, halogen, hydroxy, alkyl, alkoxy; R5and R6one, or both, can also be oxoprop when they are linked to the carbon atom; when R5and R6linked to the nitrogen atom, they represent a hydrogen, hydroxy or unsubstituted group selected from alkyl, alkoxy, aralkyl; x is the heteroatom selected from oxygen or sulfur; Ar denotes unsubstituted divalent phenylene, naftilan or benzofuran; R7forms a link with a neighboring group, R8; R9means hydrogen or unsubstituted group selected from alkyl, aryl; R10means hydrogen or unsubstituted group selected from alkyl, aryl; Y represents oxygen; n is an integer from 1 to 4; m is an integer 1, comprising the reaction of compounds of formula (IIIj)

where R1, R2, R3, R4, R5, R6, X, and n have the above meanings, with a compound of formula (IIIi)

where R7and R8together is the form a chemical bond; R9, R10and Ar are as defined above values; obtaining videopreteen the compounds of formula (I), and, optionally, converting the compounds of formula (I) into a pharmaceutically acceptable salt or pharmaceutically acceptable MES.

6. The method of obtaining the compounds of formula (I)

its tautomeric forms, stereoisomers, polymorphic forms, pharmaceutically acceptable salts, pharmaceutically acceptable solvate, where the group R1, R2, R3, R4group and R5and R6when they are connected to carbon atoms, represent hydrogen, halogen, hydroxy, alkyl, alkoxy; R5and R6one, or both, can also be oxoprop when they are linked to the carbon atom; when R5and R6linked to the nitrogen atom, they represent a hydrogen, hydroxy or unsubstituted group selected from alkyl, alkoxy, aralkyl; x is the heteroatom selected from oxygen or sulfur; Ar denotes unsubstituted divalent phenylene, naftilan or benzofuran; R7and R8each means hydrogen, R9means hydrogen or unsubstituted group selected from alkyl, aryl; R10means hydrogen or unsubstituted group selected from alkyl, aryl; Y represents oxygen; n is an integer from 1 to 4; m is an integer 1, including the restore the compounds of formula (IVa)

where R1, R2, R3, R4, R5, R6, R9, R10, Ar, X, n and m have the above meanings, with getting videopreteen the compounds of formula (I) and, optionally, the separation of the compounds of formula (I), its stereoisomers, and, optionally, converting the obtained compound of formula (I) or its stereoisomers in pharmaceutically acceptable salt or pharmaceutically acceptable MES.

7. The method of obtaining the compounds of formula (I)

its tautomeric forms, stereoisomers, polymorphic forms, pharmaceutically acceptable salts, pharmaceutically acceptable solvate, where the group R1, R2, R3, R4group and R5and R6when they are connected to carbon atoms, represent hydrogen, halogen, hydroxy, alkyl, alkoxy; R5and R6one, or both, can also be oxoprop when they are linked to the carbon atom; when R5and R6linked to the nitrogen atom, they represent a hydrogen, hydroxy or unsubstituted group selected from alkyl, alkoxy, aralkyl; x is the heteroatom selected from oxygen or sulfur; Ar denotes unsubstituted divalent phenylene, naftilan or benzofuran; R7means hydrogen, alkoxy, Nissi is alkyl; R8means hydrogen, lower alkyl, unsubstituted or substituted aralkyl; R9means hydrogen or unsubstituted group selected from alkyl, aryl; R10means hydrogen or unsubstituted group selected from alkyl, aryl; Y represents oxygen; n is an integer from 1 to 4; m is an integer 1, comprising the reaction of compounds of formula (IIIh)

where R1, R2, R3, R4, R5, R6, X and n have the above meanings, L1means delete the group with the compound of the formula (IIIi)

where R7, R8, R9, R10and Ar are as defined above values, obtaining videopreteen the compounds of formula (I) and, optionally, the separation of the compounds of formula (I), its stereoisomers, and, optionally, converting the compounds of formula (I) or its stereoisomers in pharmaceutically acceptable salt or pharmaceutically acceptable MES.

8. The method of obtaining the compounds of formula (I)

its tautomeric forms, stereoisomers, polymorphic forms, pharmaceutically acceptable salts, pharmaceutically acceptable solvate, where the group R1, R2, R3, R4group and R5and R6when they are linked to the carbon atoms, to depict ablaut a hydrogen, halogen, hydroxy, alkyl, alkoxy; R5and R6one, or both, can also be oxoprop when they are linked to the carbon atom; when R5and R6linked to the nitrogen atom, they represent a hydrogen, hydroxy or unsubstituted group selected from alkyl, alkoxy, aralkyl; x is the heteroatom selected from oxygen or sulfur; Ar denotes unsubstituted divalent phenylene, naftilan or benzofuran; R7means hydrogen, alkoxy, lower alkyl; R8means hydrogen, lower alkyl, substituted or unsubstituted aralkyl; R9means hydrogen or unsubstituted group selected from alkyl, aryl; R10means hydrogen or unsubstituted group selected from alkyl, aryl; Y represents oxygen; n is an integer from 1 to 4; m is an integer 1, comprising the reaction of compounds of formula (IIIj)

where R1, R2, R3, R4, R5, R6, X, and n have the above meanings, with a compound of formula (IIIi)

where R7, R8, R9, R10and Ar are as defined above values, obtaining videopreteen the compounds of formula (I), and, optionally, the separation of the compounds of formula (I), its stereoisomers, and, optionally, converting the compounds of formula (I) or its stereo is the Windows in pharmaceutically acceptable salt or pharmaceutically acceptable MES.

9. The method of obtaining the compounds of formula (I)

its tautomeric forms, stereoisomers, polymorphic forms, pharmaceutically acceptable salts, pharmaceutically acceptable solvate, where the group R1, R2, R3, R4group and R5and R6when they are connected to carbon atoms, represent hydrogen, halogen, hydroxy, alkyl, alkoxy; R5and R6one, or both, can also be oxoprop when they are linked to the carbon atom; when R5and R6linked to the nitrogen atom, they represent a hydrogen, hydroxy or unsubstituted group selected from alkyl, alkoxy, aralkyl; x is the heteroatom selected from oxygen or sulfur; Ar denotes unsubstituted divalent phenylene, naftilan or benzofuran; R7means hydrogen, alkoxy, lower alkyl; R8means hydrogen, lower alkyl, substituted or unsubstituted aralkyl; R9means hydrogen or unsubstituted group selected from alkyl, aryl; R10means hydrogen or unsubstituted group selected from alkyl, aryl; Y represents oxygen; n is an integer from 1 to 4; m is an integer 1, comprising the reaction of compounds of formula (IVd)

where R1, R2, R3, R4, R5, R6, R7, R810, Ar, X, n and m have videopreteen values, with the compound of formula (IIVe)

where R9means hydrogen or unsubstituted group selected from alkyl or aryl; L2means halogen; obtaining videopreteen the compounds of formula (I), and optional separation of the compounds of formula (I), its stereoisomers, and, optionally, converting the compounds of formula (I) or its stereoisomers in pharmaceutically acceptable salt or pharmaceutically acceptable MES.

10. The method of obtaining the compounds of formula (I)

its tautomeric forms, stereoisomers, polymorphic forms, pharmaceutically acceptable salts, pharmaceutically acceptable solvate, where the group R1, R2, R3, R4group and R5and R6when they are connected to carbon atoms, represent hydrogen, halogen, hydroxy, alkyl, alkoxy; R5and R6one, or both, can also be oxoprop when they are linked to the carbon atom; when R5and R6linked to the nitrogen atom, they represent a hydrogen, hydroxy or unsubstituted group selected from alkyl, alkoxy, aralkyl; x is the heteroatom selected from oxygen or sulfur; Ar denotes unsubstituted divalent phenylene, naftilan or benzo is furyl; R7means a hydrogen atom, alkoxy, lower alkyl or forms a bond with a neighboring group, R8; R8means hydrogen, lower alkyl, unsubstituted or substituted aralkyl or forms a bond with R7; R9means hydrogen or unsubstituted group selected from alkyl, aryl; R10means hydrogen or unsubstituted group selected from alkyl, aryl; Y represents NR12where R12means hydrogen, alkyl; n is an integer from 1 to 4; m is an integer 1, comprising the reaction of compounds of formula (I)

where R1, R2, R3, R4, R5, R6, R7, R8, R9, Ar, X, n and m have the above meanings; Y represents oxygen, YR10means halogen, or COYR10is a mixed anhydride, with an appropriate amine of the formula with other10R12where R10and R12have videopreteen values and, optionally, the separation of the compounds of formula (I), the stereoisomers, and, optionally, converting the obtained compound of formula (I) or its stereoisomers in pharmaceutically acceptable salt or pharmaceutically acceptable MES.

11. Substituted bicyclic heterocyclic compound of the formula (I)

its tautomeric forms, stereoisomers, Polym hnye form, pharmaceutically acceptable salt, pharmaceutically acceptable solvate, where the group R1, R2, R3, R4group and R5and R6when they are connected to carbon atoms, represent hydrogen, halogen, hydroxy, alkyl, alkoxy; R5and R6one, or both, can also be oxoprop when they are linked to the carbon atom; when R5and R6linked to the nitrogen atom, they represent a hydrogen, hydroxy or unsubstituted group selected from alkyl, alkoxy, aralkyl; x is the heteroatom selected from oxygen or sulfur; Ar denotes unsubstituted divalent phenylene, naftilan or benzofuran; R7forms a link with the group R8; R9means hydrogen or unsubstituted group selected from alkyl, aryl; R10means hydrogen or unsubstituted group selected from alkyl, aryl; Y represents oxygen; n is an integer from 1 to 4; m is an integer 1, obtained by the method according to any of claim 2 through 5.

12. Substituted bicyclic heterocyclic compound of the formula (I)

its tautomeric forms, stereoisomers, polymorphic forms, pharmaceutically acceptable salt, pharmaceutically acceptable solvate, where the group R1, R2, R3, R4group and R5and R6when they are connected to carbon atoms, predstavlyaet a hydrogen, halogen, hydroxy, alkyl, alkoxy; R5and R6one, or both, can also be oxoprop when they are linked to the carbon atom; when R5and R6linked to the nitrogen atom, they represent a hydrogen, hydroxy or unsubstituted group selected from alkyl, alkoxy, aralkyl; x is the heteroatom selected from oxygen or sulfur; Ar denotes unsubstituted divalent phenylene, naftilan or benzofuran; R7means hydrogen, alkoxy, lower alkyl; R8means hydrogen, lower alkyl, substituted or unsubstituted aralkyl; R9means hydrogen or unsubstituted group selected from alkyl, aryl; R10means hydrogen or unsubstituted group selected from alkyl, aryl; Y represents oxygen; n is an integer from 1 to 4; m is an integer 1, obtained by the method according to any of PP-9.

13. Substituted bicyclic heterocyclic compound of the formula (I)

its tautomeric forms, stereoisomers, polymorphic forms, pharmaceutically acceptable salt, pharmaceutically acceptable solvate, where the group R1, R2, R3, R4group and R5and R6when they are connected to carbon atoms, represent hydrogen, halogen, hydroxy, alkyl, alkoxy; R5and R6one or both may also represent an oxo is the Rupp, when they are linked to the carbon atom; when R5and R6linked to the nitrogen atom, they represent a hydrogen, hydroxy or unsubstituted group selected from alkyl, alkoxy, aralkyl; x is the heteroatom selected from oxygen or sulfur; Ar denotes unsubstituted divalent phenylene, naftilan or benzofuran; R7means a hydrogen atom, alkoxy, lower alkyl or forms a bond with a neighboring group, R8; R8means hydrogen, lower alkyl, unsubstituted or substituted aralkyl, or forms a bond with R7; R9means hydrogen or unsubstituted group selected from alkyl, aryl; R10means hydrogen or unsubstituted group selected from alkyl, aryl; Y represents NR12where R12means hydrogen, alkyl; n is an integer from 1 to 4; m is an integer 1, obtained by the method according to claim 10.

14. The compound according to claim 1, selected from the group

(E/Z)-3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid, ethyl ester;

(E)-3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid, ethyl ester;

(Z)-3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid, ethyl ester;

(±)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid, methyl ester;

(+)3-[4-[2-(2,3-dihydro-1,4-benzoxa is n-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid, methyl ether;

(-)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid, methyl ester;

(E/Z)-3-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)methylbenzofuran-5-yl]-2-ethoxypropanol acid, ethyl ester;

(E)-3-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)methylbenzofuran-5-yl]-2-ethoxypropanol acid, ethyl ester;

(Z)-3-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)methylbenzofuran-5-yl]-2-ethoxypropanol acid, ethyl ester;

(E/Z)-3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid, ethyl ester;

(E)-3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid, ethyl ester;

(Z)-3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid, ethyl ester;

(±)-3-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)methylbenzofuran-5-yl]-2-ethoxypropanol acid, methyl ester;

(±)3-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)methylbenzofuran-5-yl]-2-ethoxypropanol acid, methyl ester;

(-)3-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)methylbenzofuran-5-yl]-2-ethoxypropanol acid, methyl ester;

(±)3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid, methyl ester;

(+)3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid, methyl ester;

(-)3-[-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid, methyl ether;

(±)2-methyl-3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid, methyl ester;

(+)- 2-methyl-3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid, methyl ester;

(- )- 2-methyl-3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid, methyl ester;

(±)2-(2-forebesi)-3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid, methyl ester;

(+)2-(2-forebesi)-3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid, methyl ester;

(-)2-(2-forebesi)-3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid, methyl ester;

(E/Z)-3-[4-[2-(3-oxo-2H-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid, ethyl ester;

(E)-3-[4-[2-(3-oxo-2H-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid, ethyl ester;

(Z)-3-[4-[2-(3-oxo-2H-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid, ethyl ester;

(±)3-[4-[2-(3-oxo-2H-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid, methyl ester;

(+)3-[4-[2-(3-oxo-2H-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid, methyl ester;

(-)3-[4-[2-(3-oxo-2H-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid, methyl who FYR;

(E/Z)-3-[6-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]naphthyl]-2-ethoxypropanol acid, ethyl ester;

(E)-3-[6-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]naphthyl]-2-ethoxypropanol acid, ethyl ester;

(Z)-3-[6-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]naphthyl]-2-ethoxypropanol acid, ethyl ester;

(±)3-[6-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]naphthyl]-2-ethoxypropanol acid, methyl ester;

(+)3-[6-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]naphthyl]-2-ethoxypropanol acid, methyl ester;

(-)3-[6-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]naphthyl]-2-ethoxypropanol acid, methyl ester;

(±)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-hydroxypropanoic acid, ethyl ester;

(+)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-hydroxypropanoic acid, ethyl ester;

(-)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-hydroxypropanoic acid, ethyl ester;

(±)3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-hydroxypropanoic acid, ethyl ester;

(+)3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-hydroxypropanoic acid, ethyl ester;

(-)3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-hydroxypropanoic acid, ethyl ester;

(±)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)e is the hydroxy]phenyl]-2-benzyloxypropionic acid, ethyl ether;

(+)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-benzyloxypropionic acid, ethyl ester;

(-)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-benzyloxypropionic acid, ethyl ester;

(±)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-butoxypropan acid, ethyl ester;

(+)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-butoxypropan acid, ethyl ester;

(-)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-butoxypropan acid, ethyl ester;

(±)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-hexyloxyphenol acid, ethyl ester;

(+)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-hexyloxyphenol acid, ethyl ester;

(-)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-hexyloxyphenol acid, ethyl ester;

(±)(E/Z)-3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-phenoxypropanol acid, ethyl ester;

(+)(E)-3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-phenoxypropanol acid, ethyl ester;

(-)(Z)-3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-phenoxypropanol acid, ethyl ester;

(±)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-phenoxypropanol acid, methyl ester;

(+)3-[4-[2-(2,3-d the hydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-phenoxypropanol acid, methyl ether;

(-)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-phenoxypropanol acid, methyl ester;

(E/Z)-3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-phenoxypropanol acid, ethyl ester;

(E)-3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-phenoxypropanol acid, ethyl ester;

(Z)-3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-phenoxypropanol acid, ethyl ester;

(±)3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-phenoxypropanol acid, methyl ester;

(+)3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-phenoxypropanol acid, methyl ester;

(-)3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-phenoxypropanol acid, methyl ester;

(E/Z)-3-[4-(4-methyl-3,4-dihydro-1,4-benzoxazin-2-yl)methoxyphenyl]-2-ethoxypropanol acid, ethyl ester;

(E)-3-[4-(4-methyl-3,4-dihydro-1,4-benzoxazin-2-yl)methoxyphenyl]-2-ethoxypropanol acid, ethyl ester;

(Z)-3-[4-(4-methyl-3,4-dihydro-1,4-benzoxazin-2-yl)methoxyphenyl]-2-ethoxypropanol acid, ethyl ester;

(±)3-[4-(4-methyl-3,4-dihydro-1,4-benzoxazin-2-yl)methoxyphenyl]-2-ethoxypropanol acid, methyl ester;

(+)3-[4-(4-methyl-3,4-dihydro-1,4-benzoxazin-2-yl)methoxyphenyl]-2-ethoxypropanol acid, methyl ester;

(-)3-[4-(methyl-3,4-dihydro-1,4-benzoxazin-2-yl)methoxyphenyl]-2-ethoxypropanol acid, methyl ether;

(E/Z)-3-[4-(4-benzyl-3,4-dihydro-1,4-benzoxazin-2-yl)methoxyphenyl]-2-ethoxypropanol acid, ethyl ester;

(E)-3-[4-(4-benzyl-3,4-dihydro-1,4-benzoxazin-2-yl)methoxyphenyl]-2-ethoxypropanol acid, ethyl ester;

(Z)-3-[4-(4-benzyl-3,4-dihydro-1,4-benzoxazin-2-yl)methoxyphenyl]-2-ethoxypropanol acid, ethyl ester;

(±)3-[4-(4-benzyl-3,4-dihydro-1,4-benzoxazin-2-yl)methoxyphenyl]-2-ethoxypropanol acid, methyl ester;

(+)3-[4-(4-benzyl-3,4-dihydro-1,4-benzoxazin-2-yl)methoxyphenyl]-2-ethoxypropanol acid, methyl ester;

(-)3-[4-(4-benzyl-3,4-dihydro-1,4-benzoxazin-2-yl)methoxyphenyl]-2-ethoxypropanol acid, methyl ester;

(±)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid and its salts;

(+)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid and its salts;

(-)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid and its salts;

(±)3-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)methylbenzofuran-5-yl]-2-ethoxypropanol acid and its salts;

(+)3-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)methylbenzofuran-5-yl]-2-ethoxypropanol acid and its salts;

(-)3-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)methylbenzofuran-5-yl]-2-ethoxypropanol acid and its salts;

(±)3-[2-(2,3-dihydr the -1,4-benzothiazin-4-yl)methylbenzofuran-5-yl]-2-ethoxypropanol acid and its salts;

(+)3-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)methylbenzofuran-5-yl]-2-ethoxypropanol acid and its salts;

(-)3-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)methylbenzofuran-5-yl]-2-ethoxypropanol acid and its salts;

(±)3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid and its salts;

(+)3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid and its salts;

(-)3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid and its salts;

(±)3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-ethoxypropane;

(+)3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-ethoxypropane;

(-)3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-ethoxypropane;

(±)N-methyl-3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-ethoxypropane;

(+)N-methyl-3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-stateprovided;

(-)N-methyl-3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-ethoxypropane;

(±)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropane;

(+)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropane;

(-)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropane;

(±)N-methyl-3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-ethoxypropane;

(+)N-methyl-3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropane;

(-)N-methyl-3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropane;

(±)N-benzyl-3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropane;

(+)N-benzyl-3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropane;

(-)N-benzyl-3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropane;

(±)N-benzyl-3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-ethoxypropane;

(+)N-benzyl-3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-ethoxypropane;

(-)N-benzyl-3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-ethoxypropane;

(±)2-methyl-3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid and its salts;

(+)- 2-methyl-3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid and its salts;

(- )- 2-methyl-3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid and its salts;

(±)2-(2-forebesi)-3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy] phenyl]-2-ethoxypropanol acid and its salts;

(+)2-(2-forebesi)-3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid and its salts;

(-)2-(2-forebesi)-3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ATOC and]phenyl]-2-ethoxypropanol acid and its salts;

(±)3-[4-[2-(3-oxo-2H-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid and its salts;

(+)3-[4-[2-(3-oxo-2H-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid and its salts;

(-)3-[4-[2-(3-oxo-2H-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid and its salts;

(±)3-[4-[2-(3-oxo-2H-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid and its salts;

(+)3-[4-[2-(3-oxo-2H-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid and its salts;

(-)3-[4-[2-(3-oxo-2H-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid and its salts;

(±)3-[6-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]naphthyl]-2-ethoxypropanol acid and its salts;

(+)3-[6-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]naphthyl]-2-ethoxypropanol acid and its salts;

(-)3-[6-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]naphthyl]-2-ethoxypropanol acid and its salts;

(±)3-[6-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]naphthyl]-2-ethoxypropanol acid and its salts;

(+)3-[6-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]naphthyl]-2-ethoxypropanol acid and its salts;

(-)3-[6-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]naphthyl]-2-ethoxypropanol acid and its salts;

(±)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-hydroxypropanoic acid and its salts;

(+)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-the l)ethoxy]phenyl]-2-hydroxypropanoic acid and its salts;

(-)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-hydroxypropanoic acid and its salts;

(±)3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-hydroxypropanoic acid and its salts;

(+)3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-hydroxypropanoic acid and its salts;

(-)3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-hydroxypropanoic acid and its salts;

(±)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-benzyloxypropionic acid and its salts;

(+)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-benzyloxypropionic acid and its salts;

(-)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-benzyloxypropionic acid and its salts;

(±)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-butoxypropan acid and its salts;

(+)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-butoxypropan acid and its salts;

(-)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-butoxypropan acid and its salts;

(±)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-hexyloxyphenol acid and its salts;

(+)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-hexyloxyphenol acid and its salts;

(-)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-hexyloxyphenol acid and its salts;

(±)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-phenoxypropanol acid and its salts;

(+)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-phenoxypropanol acid and its salts;

(-)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-phenoxypropanol acid and its salts;

(±)3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-phenoxypropanol acid and its salts;

(+)3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-phenoxypropanol acid and its salts;

(-)3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-phenoxypropanol acid and its salts;

(±)2-methyl-3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-phenoxypropanol acid, methyl ester;

(+)- 2-methyl-3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-phenoxypropanol acid, methyl ester;

(- )- 2-methyl-3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-phenoxypropanol acid, methyl ester;

(±)2-methyl-3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-phenoxypropanol acid and its salts;

(+)- 2-methyl-3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-phenoxypropanol acid and its salts;

(- )- 2-methyl-3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-phenoxypropanol acid and its salts;

(±)2-methyl-3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-Fe is oxopropanoic acid, methyl ether;

(+)- 2-methyl-3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-phenoxypropanol acid, methyl ester;

(- )- 2-methyl-3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-phenoxypropanol acid, methyl ester;

(±)2-methyl-3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-phenoxypropanol acid and its salts;

(+)- 2-methyl-3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-phenoxypropanol acid and its salts;

(- )- 2-methyl-3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-phenoxypropanol acid and its salts;

(±)3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid, 4-nitrophenyloctyl ether;

(+)3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid, 4-nitrophenyloctyl ether;

(-)3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid, 4-nitrophenyloctyl ether;

(±)3-[4-(4-benzyl-3,4-dihydro-1,4-benzoxazin-2-yl)methoxyphenyl]-2-ethoxypropanol acid and its salts;

(+)3-[4-(4-benzyl-3,4-dihydro-1,4-benzoxazin-2-yl)methoxyphenyl]-2-ethoxypropanol acid and its salts;

(-)3-[4-(4-benzyl-3,4-dihydro-1,4-benzoxazin-2-yl)methoxyphenyl]-2-ethoxypropanol acid and its salts;

(±)3-[4-(4-benzyl-3,4-dihydro-1,4-benzoxazin-2-yl)methoxyphenyl]-2-ethoxypropanol acid, 4-nitro niloy ether;

(+)3-[4-(4-benzyl-3,4-dihydro-1,4-benzoxazin-2-yl)methoxyphenyl]-2-ethoxypropanol acid, 4-nitrophenyloctyl ether;

(-)3-[4-(4-benzyl-3,4-dihydro-1,4-benzoxazin-2-yl)methoxyphenyl]-2-ethoxypropanol acid, 4-nitrophenyloctyl ether.

15. The compound according to claim 1, in which the pharmaceutically acceptable salt is a salt of Li, Na, K, CA, Mg, Fe, Cu, Zn, Mn, N,N'-diacetylethylenediamine, betaine, caffeine, 2-Diethylaminoethanol, 2-dimethylaminoethanol, N-ethylmorpholine, N-ethylpiperidine, glucamine, glucosamine, geranamine, Isopropylamine, methylglucamine, research, piperazine, piperidine, procaine, purines, theobromine, triethylamine, trimethylamine, Tripropylamine, tromethamine, diethanolamine, meglumine, Ethylenediamine, N,N'-diphenylethylenediamine, N,N'-dibenziletilendiaminom, N-benzylpenicillin, choline, choline hydroxide, dicyclohexylamine, benzylamine, phenethylamine, dialkylamino, trialkylamine, thiamine, aminopyrimidine, aminopyridine, purine, spermidine, alkylenediamine, glycinol, phenylglycinol, glycine, alanine, valine, leucine, isoleucine, norleucine, tyrosine, cystine, cysteine, methionine, Proline, hydroxyproline, histidine, ornithine, lysine, arginine, serine, threonine, phenylalanine, guanidine, substituted guanidine, ammonium, substituted ammonium or aluminum.

16. The compound according to claim 1 or 26, representing the Wallpaper any of the salts of Li, Na, K, CA, Mg, Fe, Cu, Zn, Mn, N,N'-diacetylethylenediamine, betaine, caffeine, 2-Diethylaminoethanol, 2-dimethylaminoethanol, N-ethylmorpholine, N-ethylpiperidine, glucamine, glucosamine, geranamine, Isopropylamine, methylglucamine, research, piperazine, piperidine, procaine, purines, theobromine, triethylamine, trimethylamine, Tripropylamine, tromethamine, diethanolamine, meglumine, Ethylenediamine, N,N'-diphenylethylenediamine, N,N'-dibenziletilendiaminom, N-benzylpenicillin, choline, kolingerova, dicyclohexylamine, benzylamine, phenethylamine, dialkylamino, trialkylamine, thiamine, aminopyrimidine, aminopyridine, purine, spermidine, alkylenediamine, glycinol, phenylglycinol, glycine, alanine, valine, leucine, isoleucine, norleucine, tyrosine, cystine, cysteine, methionine, Proline, hydroxyproline, histidine, ornithine, lysine, arginine, serine, threonine, phenylalanine, guanidine, substituted guanidine, ammonium, substituted ammonium or aluminum salts, educated (±)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid;

any of the salts of Li, Na, K, CA, Mg, Fe, Cu, Zn, Mn, N,N'-diacetylethylenediamine, betaine, caffeine, 2-Diethylaminoethanol, 2-dimethylaminoethanol, N-ethylmorpholine, N-ethylpiperidine, glucamine, glucosamine, geranamine, Isopropylamine, methylglucamine, research, piperazine, Pieper is Dina, of procaine, purines, theobromine, triethylamine, trimethylamine, Tripropylamine, tromethamine, diethanolamine, meglumine, Ethylenediamine, N,N'-diphenylethylenediamine, N,N'-dibenziletilendiaminom, N-benzylpenicillin, choline, kolingerova, dicyclohexylamine, benzylamine, phenethylamine, dialkylamino, trialkylamine, thiamine, aminopyrimidine, aminopyridine, purine, spermidine, alkylenediamine, glycinol, phenylglycinol, glycine, alanine, valine, leucine, isoleucine, norleucine, tyrosine, cystine, cysteine, methionine, Proline, hydroxyproline, histidine, ornithine, lysine, arginine, serine, threonine, phenylalanine, guanidine, substituted guanidine, ammonium, substituted ammonium and aluminium, educated (+)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid;

any of the salts of Li, Na, K, CA, Mg, Fe, Cu, Zn, Mn, N,N'-diacetylethylenediamine, betaine, caffeine, 2-Diethylaminoethanol, 2-dimethylaminoethanol, N-ethylmorpholine, N-ethylpiperidine, glucamine, glucosamine, geranamine, Isopropylamine, methylglucamine, research, piperazine, piperidine, procaine, purines, theobromine, triethylamine, trimethylamine, Tripropylamine, tromethamine, diethanolamine, meglumine, Ethylenediamine, N,N'-diphenylethylenediamine, N,N'-dibenziletilendiaminom, N-benzylpenicillin, choline, kolingerova, dicyclohexylamine, Benz is lamina, of phenethylamine, dialkylamino, trialkylamine, thiamine, aminopyrimidine, aminopyridine, purine, spermidine, alkylenediamine, glycinol, phenylglycinol, glycine, alanine, valine, Lapina, isoleucine, norleucine, tyrosine, cystine, cysteine, methionine, Proline, hydroxyproline, histidine, ornithine, lysine, arginine, serine, threonine, phenylalanine, guanidine, substituted guanidine, ammonium, substituted ammonium and aluminum formed (-)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid;

any of the salts of Li, Na, K, CA, Mg, Fe, Cu, Zn, Mn, N,N'-diacetylethylenediamine, betaine, caffeine, 2-Diethylaminoethanol, 2-dimethylaminoethanol, N-ethylmorpholine, N-ethylpiperidine, glucamine, glucosamine, geranamine, Isopropylamine, methylglucamine, research, piperazine, piperidine, procaine, purines, theobromine, triethylamine, trimethylamine, Tripropylamine, tromethamine, diethanolamine, meglumine, Ethylenediamine, N,N'-diphenylethylenediamine, N,N'-dibenziletilendiaminom, N-benzylpenicillin, choline, kolingerova, dicyclohexylamine, benzylamine, phenethylamine, dialkylamino, trialkylamine, thiamine, aminopyrimidine, aminopyridine, purine, spermidine, alkylenediamine, glycinol, phenylglycinol, glycine, alanine, valine, leucine, isoleucine, norleucine, tyrosine, cystine, cysteine, methionine, Proline, is hydroxyproline, histidine, ornithine, lysine, arginine, serine, threonine, phenylalanine, guanidine, substituted guanidine, ammonium, substituted ammonium and aluminium, educated (±)3-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)methylbenzofuran-5-yl]-2-ethoxypropanol acid;

any of the salts of Li, Na, K, CA, Mg, Fe, Cu, Zn, Mn, N,N'-diacetylethylenediamine, betaine, caffeine, 2-Diethylaminoethanol, 2-dimethylaminoethanol, N-ethylmorpholine, N-ethylpiperidine, glucamine, glucosamine, geranamine, Isopropylamine, methylglucamine, research, piperazine, piperidine, procaine, purines, theobromine, triethylamine, trimethylamine, Tripropylamine, tromethamine, diethanolamine, meglumine, Ethylenediamine, N,N'-diphenylethylenediamine, N,N'-dibenziletilendiaminom, N-benzylpenicillin, choline, kolingerova, dicyclohexylamine, benzylamine, phenethylamine, dialkylamino, trialkylamine, thiamine, aminopyrimidine, aminopyridine, purine, spermidine, alkylenediamine, glycinol, phenylglycinol, glycine, alanine, valine, leucine, isoleucine, norleucine, tyrosine, cystine, cysteine, methionine, Proline, hydroxyproline, histidine, ornithine, lysine, arginine, serine, threonine, phenylalanine, guanidine, substituted guanidine, ammonium, substituted ammonium and aluminium, educated (+)3-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)methylbenzofuran-5-yl]-2-ethoxypropanol acid;

any of the salts of Li, Na, K, CA, Mg, Fe, Cu, Zn, Mn, N,N'-diacetylethylenediamine, betaine, caffeine, 2-Diethylaminoethanol, 2-dimethylaminoethanol, N-ethylmorpholine, N-ethylpiperidine, glucamine, glucosamine, geranamine, Isopropylamine, methylglucamine, research, piperazine, piperidine, procaine, purines, theobromine, triethylamine, trimethylamine, Tripropylamine, tromethamine, diethanolamine, meglumine, Ethylenediamine, N,N'-diphenylethylenediamine, N,N'-dibenziletilendiaminom, N-benzylpenicillin, choline, kolingerova, dicyclohexylamine, benzylamine, phenethylamine, dialkylamino, trialkylamine, thiamine, aminopyrimidine, aminopyridine, purine, spermidine, alkylenediamine, glycinol, phenylglycinol, glycine, alanine, valine, leucine, isoleucine, norleucine, tyrosine, cystine, cysteine, methionine, Proline, hydroxyproline, histidine, ornithine, lysine, arginine, serine, threonine, phenylalanine, guanidine, substituted guanidine, ammonium, substituted ammonium and aluminum formed (-)3-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)methylbenzofuran-5-yl]-2-ethoxypropanol acid;

any of the salts of Li, Na, K, CA, Mg, Fe, Cu, Zn, Mn, N,N'-diacetylethylenediamine, betaine, caffeine, 2-Diethylaminoethanol, 2-dimethylaminoethanol, N-ethylmorpholine, N-ethylpiperidine, glucamine, glucosamine, geranamine, Isopropylamine, methylglucamine, research, piperazine, n is peridine, of procaine, purines, theobromine, triethylamine, trimethylamine, Tripropylamine, tromethamine, diethanolamine, meglumine, Ethylenediamine, N,N'-diphenylethylenediamine, N,N'-dibenziletilendiaminom, N-benzylpenicillin, choline, kolingerova, dicyclohexylamine, benzylamine, phenethylamine, dialkylamino, trialkylamine, thiamine, aminopyrimidine, aminopyridine, purine, spermidine, alkylenediamine, glycinol, phenylglycinol, glycine, alanine, valine, leucine, isoleucine, norleucine, tyrosine, cystine, cysteine, methionine, Proline, hydroxyproline, histidine, ornithine, lysine, arginine, serine, threonine, phenylalanine, guanidine, substituted guanidine, ammonium, substituted ammonium and aluminium, educated (±)3-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)methylbenzofuran-5-yl]-2-ethoxypropanol acid;

any of the salts of Li, Na, K, CA, Mg, Fe, Cu, Zn, Mn, N,N'-diacetylethylenediamine, betaine, caffeine, 2-Diethylaminoethanol, 2-dimethylaminoethanol, N-ethylmorpholine, N-ethylpiperidine, glucamine, glucosamine, geranamine, Isopropylamine, methylglucamine, research, piperazine, piperidine, procaine, purines, theobromine, triethylamine, trimethylamine, Tripropylamine, tromethamine, diethanolamine, meglumine, Ethylenediamine, N,N'-diphenylethylenediamine, N,N'-dibenziletilendiaminom, N-benzylpenicillin, choline, kolingerova, DICYCLOHEXYL the ina, benzylamine, phenethylamine, dialkylamino, trialkylamine, thiamine, aminopyrimidine, aminopyridine, purine, spermidine, alkylenediamine, glycinol, phenylglycinol, glycine, alanine, valine, leucine, isoleucine, norleucine, tyrosine, cystine, cysteine, methionine, Proline, hydroxyproline, histidine, ornithine, lysine, arginine, serine, threonine, phenylalanine, guanidine, substituted guanidine, ammonium, substituted ammonium and aluminium, educated (+)3-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)methylbenzofuran-5-yl]-2-ethoxypropanol acid;

any of the salts of Li, Na, K, CA, Mg, Fe, Cu, Zn, Mn, N,N'-diacetylethylenediamine, betaine, caffeine, 2-Diethylaminoethanol, 2-dimethylaminoethanol, N-ethylmorpholine, N-ethylpiperidine, glucamine, glucosamine, geranamine, Isopropylamine, methylglucamine, research, piperazine, piperidine, procaine, purines, theobromine, triethylamine, trimethylamine, Tripropylamine, tromethamine, diethanolamine, meglumine, Ethylenediamine, N,N'-diphenylethylenediamine, N,N'-dibenziletilendiaminom, N-benzylpenicillin, choline, kolingerova, dicyclohexylamine, benzylamine, phenethylamine, dialkylamino, trialkylamine, thiamine, aminopyrimidine, aminopyridine, purine, spermidine, alkylenediamine, glycinol, phenylglycinol, glycine, alanine, valine, leucine, isoleucine, norleucine, tyrosine, cystine, cysteine, m is thionine, Proline, hydroxyproline, histidine, ornithine, lysine, arginine, serine, threonine, phenylalanine, guanidine, substituted guanidine, ammonium, substituted ammonium and aluminum formed (-)3-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)methylbenzofuran-5-yl]-2-ethoxypropanol acid;

any of the salts of Li, Na, K, CA, Mg, Fe, Cu, Zn, Mn, N,N'-diacetylethylenediamine, betaine, caffeine, 2-Diethylaminoethanol, 2-dimethylaminoethanol, N-ethylmorpholine, N-ethylpiperidine, glucamine, glucosamine, geranamine, Isopropylamine, methylglucamine, research, piperazine, piperidine, procaine, purines, theobromine, triethylamine, trimethylamine, Tripropylamine, tromethamine, diethanolamine, meglumine, Ethylenediamine, N,N'-diphenylethylenediamine, N,N'-dibenziletilendiaminom, N-benzylpenicillin, choline, kolingerova, dicyclohexylamine, benzylamine, phenethylamine, dialkylamino, trialkylamine, thiamine, aminopyrimidine, aminopyridine, purine, spermidine, alkylenediamine, glycinol, phenylglycinol, glycine, alanine, valine, leucine, isoleucine, norleucine, tyrosine, cystine, cysteine, methionine, Proline, hydroxyproline, histidine, ornithine, lysine, arginine, serine, threonine, phenylalanine, guanidine, substituted guanidine, ammonium, substituted ammonium and aluminium, educated (±)3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-ethoxypropan the OIC acid;

any of the salts of Li, Na, K, CA, Mg, Fe, Cu, Zn, Mn, N,N'-diacetylethylenediamine, betaine, caffeine, 2-Diethylaminoethanol, 2-dimethylaminoethanol, N-ethylmorpholine, N-ethylpiperidine, glucamine, glucosamine, geranamine, Isopropylamine, methylglucamine, research, piperazine, piperidine, procaine, purines, theobromine, triethylamine, trimethylamine, Tripropylamine, tromethamine, diethanolamine, meglumine, Ethylenediamine, N,N'-diphenylethylenediamine, N,N'-dibenziletilendiaminom, N-benzylpenicillin, choline, kolingerova, dicyclohexylamine, benzylamine, phenethylamine, dialkylamino, trialkylamine, thiamine, aminopyrimidine, aminopyridine, purine, spermidine, alkylenediamine, glycinol, phenylglycinol, glycine, alanine, valine, leucine, isoleucine, norleucine, tyrosine, cystine, cysteine, methionine, Proline, hydroxyproline, histidine, ornithine, lysine, arginine, serine, threonine, phenylalanine, guanidine, substituted guanidine, ammonium, substituted ammonium and aluminium, educated (+)3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid;

any of the salts of Li, Na, K, CA, Mg, Fe, Cu, Zn, Mn, N,N'-diacetylethylenediamine, betaine, caffeine, 2-Diethylaminoethanol, 2-dimethylaminoethanol, N-ethylmorpholine, N-ethylpiperidine, glucamine, glucosamine, geranamine, Isopropylamine, methylglucamine, research, pipers is on, piperidine, procaine, purines, theobromine, triethylamine, trimethylamine, Tripropylamine, tromethamine, diethanolamine, meglumine, Ethylenediamine, N,N'-diphenylethylenediamine, N,N'-dibenziletilendiaminom, N-benzylpenicillin, choline, kolingerova, dicyclohexylamine, benzylamine, phenethylamine, dialkylamino, trialkylamine, thiamine, aminopyrimidine, aminopyridine, purine, spermidine, alkylenediamine, glycinol, phenylglycinol, glycine, alanine, valine, leucine, isoleucine, norleucine, tyrosine, cystine, cysteine, methionine, Proline, hydroxyproline, histidine, ornithine, lysine, arginine, serine, threonine, phenylalanine, guanidine, substituted guanidine, ammonium, substituted ammonium and aluminum formed (-)3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid;

any of the salts of Li, Na, K, CA, Mg, Fe, Cu, Zn, Mn, N,N'-diacetylethylenediamine, betaine, caffeine, 2-Diethylaminoethanol, 2-dimethylaminoethanol, N-ethylmorpholine, N-ethylpiperidine, glucamine, glucosamine, geranamine, Isopropylamine, methylglucamine, research, piperazine, piperidine, procaine, purines, theobromine, triethylamine, trimethylamine, Tripropylamine, tromethamine, diethanolamine, meglumine, Ethylenediamine, N,N'-diphenylethylenediamine, N,N'-dibenziletilendiaminom, N-benzylpenicillin, choline, kolingerova, DICYCLOHEXYL the amine, benzylamine, phenethylamine, dialkylamino, trialkylamine, thiamine, aminopyrimidine, aminopyridine, purine, spermidine, alkylenediamine, glycinol, phenylglycinol, glycine, alanine, valine, leucine, isoleucine, norleucine, tyrosine, cystine, cysteine, methionine, Proline, hydroxyproline, histidine, ornithine, lysine, arginine, serine, threonine, phenylalanine, guanidine, substituted guanidine, ammonium, substituted ammonium and aluminium, educated (±)2-methyl-3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]-phenyl]-2-ethoxypropanol acid;

any of the salts of Li, Na, K, CA, Mg, Fe, Cu, Zn, Mn, N,N'-diacetylethylenediamine, betaine, caffeine, 2-Diethylaminoethanol, 2-dimethylaminoethanol, N-ethylmorpholine, N-ethylpiperidine, glucamine, glucosamine, geranamine, Isopropylamine, methylglucamine, research, piperazine, piperidine, procaine, purines, theobromine, triethylamine, trimethylamine, Tripropylamine, tromethamine, diethanolamine, meglumine, Ethylenediamine, N,N'-diphenylethylenediamine, N,N'-dibenziletilendiaminom, N-benzylpenicillin, choline, kolingerova, dicyclohexylamine, benzylamine, phenethylamine, dialkylamino, trialkylamine, thiamine, aminopyrimidine, aminopyridine, purine, spermidine, alkylenediamine, glycinol, phenylglycinol, glycine, alanine, valine, leucine, isoleucine, norleucine, tyrosine, cystine, cysts is in, methionine, Proline, hydroxyproline, histidine, ornithine, lysine, arginine, serine, threonine, phenylalanine, guanidine, substituted guanidine, ammonium, substituted ammonium and aluminium, educated (+)-2-methyl-3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]-phenyl]-2-ethoxypropanol acid;

any of the salts of Li, Na, K, CA, Mg, Fe, Cu, Zn, Mn, N,N'-diacetylethylenediamine, betaine, caffeine, 2-Diethylaminoethanol, 2-dimethylaminoethanol, N-ethylmorpholine, N-ethylpiperidine, glucamine, glucosamine, geranamine, Isopropylamine, methylglucamine, research, piperazine, piperidine, procaine, purines, theobromine, triethylamine, trimethylamine, Tripropylamine, tromethamine, diethanolamine, meglumine, Ethylenediamine, N,N'-diphenylethylenediamine, N,N'-dibenziletilendiaminom, N-benzylpenicillin, choline, kolingerova, dicyclohexylamine, benzylamine, phenethylamine, dialkylamino, trialkylamine, thiamine, aminopyrimidine, aminopyridine, purine, spermidine, alkylenediamine, glycinol, phenylglycinol, glycine, alanine, valine, leucine, isoleucine, norleucine, tyrosine, cystine, cysteine, methionine, Proline, hydroxyproline, histidine, ornithine, lysine, arginine, serine, threonine, phenylalanine, guanidine, substituted guanidine, ammonium, substituted ammonium and aluminum formed (- )-2-methyl-3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]-FeNi is]-2-ethoxypropanol acid;

any of the salts of Li, Na, K, CA, Mg, Fe, Cu, Zn, Mn, N,N'-diacetylethylenediamine, betaine, caffeine, 2-Diethylaminoethanol, 2-dimethylaminoethanol, N-ethylmorpholine, N-ethylpiperidine, glucamine, glucosamine, geranamine, Isopropylamine, methylglucamine, research, piperazine, piperidine, procaine, purines, theobromine, triethylamine, trimethylamine, Tripropylamine, tromethamine, diethanolamine, meglumine, Ethylenediamine, N,N'-diphenylethylenediamine, N,N'-dibenziletilendiaminom, N-benzylpenicillin, choline, kolingerova, dicyclohexylamine, benzylamine, phenethylamine, dialkylamino, trialkylamine, thiamine, aminopyrimidine, aminopyridine, purine, spermidine, alkylenediamine, glycinol, phenylglycinol, glycine, alanine, valine, leucine, isoleucine, norleucine, tyrosine, cystine, cysteine, methionine, Proline, hydroxyproline, histidine, ornithine, lysine, arginine, serine, threonine, phenylalanine, guanidine, substituted guanidine, ammonium, substituted ammonium and aluminium, educated (±)2-(2-forebesi)-3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid;

any of the salts of Li, Na, K, CA, Mg, Fe, Cu, Zn, Mn, N,N'-diacetylethylenediamine, betaine, caffeine, 2-Diethylaminoethanol, 2-dimethylaminoethanol, N-ethylmorpholine, N-ethylpiperidine, glucamine, glucosamine, geranamine, Isopropylamine, methylglucamine of the research, piperazine, piperidine, procaine, purines, theobromine, triethylamine, trimethylamine, Tripropylamine, tromethamine, diethanolamine, meglumine, Ethylenediamine, N,N'-diphenylethylenediamine, N,N'-dibenziletilendiaminom, N-benzylpenicillin, choline, kolingerova, dicyclohexylamine, benzylamine, phenethylamine, dialkylamino, trialkylamine, thiamine, aminopyrimidine, aminopyridine, purine, spermidine, alkylenediamine, glycinol, phenylglycinol, glycine, alanine, valine, leucine, isoleucine, norleucine, tyrosine, cystine, cysteine, methionine, Proline, hydroxyproline, histidine, ornithine, lysine, arginine, serine, threonine, phenylalanine, guanidine, substituted guanidine, ammonium, substituted ammonium and aluminium, educated (+)2-(2-forebesi)-3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid;

any of the salts of Li, Na, K, CA, Mg, Fe, Cu, Zn, Mn, N,N'-diacetylethylenediamine, betaine, caffeine, 2-Diethylaminoethanol, 2-dimethylaminoethanol, N-ethylmorpholine, N-ethylpiperidine, glucamine, glucosamine, geranamine, Isopropylamine, methylglucamine, research, piperazine, piperidine, procaine, purines, theobromine, triethylamine, trimethylamine, Tripropylamine, tromethamine, diethanolamine, meglumine, Ethylenediamine, N,N'-diphenylethylenediamine, N,N'-dibenziletilendiaminom, N-benzylpenicillin, choline, hall is hydroxide, dicyclohexylamine, benzylamine, phenethylamine, dialkylamino, trialkylamine, thiamine, aminopyrimidine, aminopyridine, purine, spermidine, alkylenediamine, glycinol, phenylglycinol, glycine, alanine, valine, leucine, isoleucine, norleucine, tyrosine, cystine, cysteine, methionine, Proline, hydroxyproline, histidine, ornithine, lysine, arginine, serine, threonine, phenylalanine, guanidine, substituted guanidine, ammonium, substituted ammonium and aluminum formed (-)2-(2-forebesi)-3-[4-[2-(2,3-dihydro 1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid;

any of the salts of Li, Na, K, CA, Mg, Fe, Cu, Zn, Mn, N,N'-diacetylethylenediamine, betaine, caffeine, 2-Diethylaminoethanol, 2-dimethylaminoethanol, N-ethylmorpholine, N-ethylpiperidine, glucamine, glucosamine, geranamine, Isopropylamine, methylglucamine, research, piperazine, piperidine, procaine, purines, theobromine, triethylamine, trimethylamine, Tripropylamine, tromethamine, diethanolamine, meglumine, Ethylenediamine, N,N'-diphenylethylenediamine, N,N'-dibenziletilendiaminom, N-benzylpenicillin, choline, kolingerova, dicyclohexylamine, benzylamine, phenethylamine, dialkylamino, trialkylamine, thiamine, aminopyrimidine, aminopyridine, purine, spermidine, alkylenediamine, glycinol, phenylglycinol, glycine, alanine, valine, leucine, isoleucine, norleucine tyrosine, cystine, cysteine, methionine, Proline, hydroxyproline, histidine, ornithine, lysine, arginine, serine, threonine, phenylalanine, guanidine, substituted guanidine, ammonium, substituted ammonium and aluminium, educated (±)3-[4-[2-(3-oxo-2H-1,4-benzoxazin-4-yl)ethoxy] phenyl]-2-ethoxypropanol acid;

any of the salts of Li, Na, K, CA, Mg, Fe, Cu, Zn, Mn, N,N'-diacetylethylenediamine, betaine, caffeine, 2-Diethylaminoethanol, 2-dimethylaminoethanol, N-ethylmorpholine, N-ethylpiperidine, glucamine, glucosamine, geranamine, Isopropylamine, methylglucamine, research, piperazine, piperidine, procaine, purines, theobromine, triethylamine, trimethylamine, Tripropylamine, tromethamine, diethanolamine, meglumine, Ethylenediamine, N,N'-diphenylethylenediamine, N,N'-dibenziletilendiaminom, N-benzylpenicillin, choline, kolingerova, dicyclohexylamine, benzylamine, phenethylamine, dialkylamino, trialkylamine, thiamine, aminopyrimidine, aminopyridine, purine, spermidine, alkylenediamine, glycinol, phenylglycinol, glycine, alanine, valine, leucine, isoleucine, norleucine, tyrosine, cystine, cysteine, methionine, Proline, hydroxyproline, histidine, ornithine, lysine, arginine, serine, threonine, phenylalanine, guanidine, substituted guanidine, ammonium, substituted ammonium and aluminium, educated (+)3-[4-[2-(3-oxo-2H 1,4-benzoxazin-4-yl)ethoxy]enyl]-2-ethoxypropanol acid;

any of the salts of Li, Na, K, CA, Mg, Fe, Cu, Zn, Mn, N,N'-diacetylethylenediamine, betaine, caffeine, 2-Diethylaminoethanol, 2-dimethylaminoethanol, N-ethylmorpholine, N-ethylpiperidine, glucamine, glucosamine, geranamine, Isopropylamine, methylglucamine, research, piperazine, piperidine, procaine, purines, theobromine, triethylamine, trimethylamine, Tripropylamine, tromethamine, diethanolamine, meglumine, Ethylenediamine, N,N'-diphenylethylenediamine, N,N'-dibenziletilendiaminom, N-benzylpenicillin, choline, kolingerova, dicyclohexylamine, benzylamine, phenethylamine, dialkylamino, trialkylamine, thiamine, aminopyrimidine, aminopyridine, purine, spermidine, alkylenediamine, glycinol, phenylglycinol, glycine, alanine, valine, leucine, isoleucine, norleucine, tyrosine, cystine, cysteine, methionine, Proline, hydroxyproline, histidine, ornithine, lysine, arginine, serine, threonine, phenylalanine, guanidine, substituted guanidine, ammonium, substituted ammonium and aluminum formed (-)3-[4-[2-(3-oxo-2H 1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid;

any of the salts of Li, Na, K, CA, Mg, Fe, Cu, Zn, Mn, N,N'-diacetylethylenediamine, betaine, caffeine, 2-Diethylaminoethanol, 2-dimethylaminoethanol, N-ethylmorpholine, N-ethylpiperidine, glucamine, glucosamine, geranamine, Isopropylamine, methylglucamine, research, piperazine is, piperidine, procaine, purines, theobromine, triethylamine, trimethylamine, Tripropylamine, tromethamine, diethanolamine, meglumine, Ethylenediamine, N,N'-diphenylethylenediamine, N,N'-dibenziletilendiaminom, N-benzylpenicillin, choline, kolingerova, dicyclohexylamine, benzylamine, phenethylamine, dialkylamino, trialkylamine, thiamine, aminopyrimidine, aminopyridine, purine, spermidine, alkylenediamine, glycinol, phenylglycinol, glycine, alanine, valine, leucine, isoleucine, norleucine, tyrosine, cystine, cysteine, methionine, Proline, hydroxyproline, histidine, ornithine, lysine, arginine, serine, threonine, phenylalanine, guanidine, substituted guanidine, ammonium, substituted ammonium and aluminium, educated (±)3-[4-[2-(3-oxo-2H-1,4-benzothiazin-4-yl)ethoxy] phenyl]-2-ethoxypropanol acid;

any of the salts of Li, Na, K, CA, Mg, Fe, Cu, Zn, Mn, N,N'-diacetylethylenediamine, betaine, caffeine, 2-Diethylaminoethanol, 2-dimethylaminoethanol, N-ethylmorpholine, N-ethylpiperidine, glucamine, glucosamine, geranamine, Isopropylamine, methylglucamine, research, piperazine, piperidine, procaine, purines, theobromine, triethylamine, trimethylamine, Tripropylamine, tromethamine, diethanolamine, meglumine, Ethylenediamine, N,N'-diphenylethylenediamine, N,N'-dibenziletilendiaminom, N-benzylpenicillin, choline, kolingerova, decollage is Ilumina, benzylamine, phenethylamine, dialkylamino, trialkylamine, thiamine, aminopyrimidine, aminopyridine, purine, spermidine, alkylenediamine, glycinol, phenylglycinol, glycine, alanine, valine, leucine, isoleucine, norleucine, tyrosine, cystine, cysteine, methionine, Proline, hydroxyproline, histidine, ornithine, lysine, arginine, serine, threonine, phenylalanine, guanidine, substituted guanidine, ammonium, substituted ammonium and aluminium, educated (+)3-[4-[2-(3-oxo-2H-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid;

any of the salts of Li, Na, K, CA, Mg, Fe, Cu, Zn, Mn, N,N'-diacetylethylenediamine, betaine, caffeine, 2-Diethylaminoethanol, 2-dimethylaminoethanol, N-ethylmorpholine, N-ethylpiperidine, glucamine, glucosamine, geranamine, Isopropylamine, methylglucamine, research, piperazine, piperidine, procaine, purines, theobromine, triethylamine, trimethylamine, Tripropylamine, tromethamine, diethanolamine, meglumine, Ethylenediamine, N,N'-diphenylethylenediamine, N,N'-dibenziletilendiaminom, N-benzylpenicillin, choline, kolingerova, dicyclohexylamine, benzylamine, phenethylamine, dialkylamino, trialkylamine, thiamine, aminopyrimidine, aminopyridine, purine, spermidine, alkylenediamine, glycinol, phenylglycinol, glycine, alanine, valine, leucine, isoleucine, norleucine, tyrosine, cystine, cysteine, methionine is, Proline, hydroxyproline, histidine, ornithine, lysine, arginine, serine, threonine, phenylalanine, guanidine, substituted guanidine, ammonium, substituted ammonium and aluminum formed (-)3-[4-[2-(3-oxo-2H-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-ethoxypropanol acid;

any of the salts of Li, Na, K, CA, Mg, Fe, Cu, Zn, Mn, N,N'-diacetylethylenediamine, betaine, caffeine, 2-Diethylaminoethanol, 2-dimethylaminoethanol, N-ethylmorpholine, N-ethylpiperidine, glucamine, glucosamine, geranamine, Isopropylamine, methylglucamine, research, piperazine, piperidine, procaine, purines, theobromine, triethylamine, trimethylamine, Tripropylamine, tromethamine, diethanolamine, meglumine, Ethylenediamine, N,N'-diphenylethylenediamine, N,N'-dibenziletilendiaminom, N-benzylpenicillin, choline, kolingerova, dicyclohexylamine, benzylamine, phenethylamine, dialkylamino, trialkylamine, thiamine, aminopyrimidine, aminopyridine, purine, spermidine, alkylenediamine, glycinol, phenylglycinol, glycine, alanine, valine, leucine, isoleucine, norleucine, tyrosine, cystine, cysteine, methionine, Proline, hydroxyproline, histidine, ornithine, lysine, arginine, serine, threonine, phenylalanine, guanidine, substituted guanidine, ammonium, substituted ammonium and aluminium, educated (±)3-[6-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]naphthyl]-2-ethoxypropanol to what slotow;

any of the salts of Li, Na, K, CA, Mg, Fe, Cu, Zn, Mn, N,N'-diacetylethylenediamine, betaine, caffeine, 2-Diethylaminoethanol, 2-dimethylaminoethanol, N-ethylmorpholine, N-ethylpiperidine, glucamine, glucosamine, geranamine, Isopropylamine, methylglucamine, research, piperazine, piperidine, procaine, purines, theobromine, triethylamine, trimethylamine, Tripropylamine, tromethamine, diethanolamine, meglumine, Ethylenediamine, N,N'-diphenylethylenediamine, N,N'-dibenziletilendiaminom, N-benzylpenicillin, choline, kolingerova, dicyclohexylamine, benzylamine, phenethylamine, dialkylamino, trialkylamine, thiamine, aminopyrimidine, aminopyridine, purine, spermidine, alkylenediamine, glycinol, phenylglycinol, glycine, alanine, valine, leucine, isoleucine, norleucine, tyrosine, cystine, cysteine, methionine, Proline, hydroxyproline, histidine, ornithine, lysine, arginine, serine, threonine, phenylalanine, guanidine, substituted guanidine, ammonium, substituted ammonium and aluminium, educated (+)3-[6-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]naphthyl]-2-ethoxypropanol acid;

any of the salts of Li, Na, K, CA, Mg, Fe, Cu, Zn, Mn, N,N'-diacetylethylenediamine, betaine, caffeine, 2-Diethylaminoethanol, 2-dimethylaminoethanol, N-ethylmorpholine, N-ethylpiperidine, glucamine, glucosamine, geranamine, Isopropylamine, methylglucamine, the research, the Pipera the ina, piperidine, procaine, purines, theobromine, triethylamine, trimethylamine, Tripropylamine, tromethamine, diethanolamine, meglumine, Ethylenediamine, N,N'-diphenylethylenediamine, N,N'-dibenziletilendiaminom, N-benzylpenicillin, choline, kolingerova, dicyclohexylamine, benzylamine, phenethylamine, dialkylamino, trialkylamine, thiamine, aminopyrimidine, aminopyridine, purine, spermidine, alkylenediamine, glycinol, phenylglycinol, glycine, alanine, valine, leucine, isoleucine, norleucine, tyrosine, cystine, cysteine, methionine, Proline, hydroxyproline, histidine, ornithine, lysine, arginine, serine, threonine, phenylalanine, guanidine, substituted guanidine, ammonium, substituted ammonium and aluminum formed (-)3-[6-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]naphthyl]-2-ethoxypropanol acid;

any of the salts of Li, Na, K, CA, Mg, Fe, Cu, Zn, Mn, N,N'-diacetylethylenediamine, betaine, caffeine, 2-Diethylaminoethanol, 2-dimethylaminoethanol, N-ethylmorpholine, N-ethylpiperidine, glucamine, glucosamine, geranamine, Isopropylamine, methylglucamine, research, piperazine, piperidine, procaine, purines, theobromine, triethylamine, trimethylamine, Tripropylamine, tromethamine, diethanolamine, meglumine, Ethylenediamine, N,N'-diphenylethylenediamine, N,N'-dibenziletilendiaminom, N-benzylpenicillin, choline, kolingerova, DICYCLOHEXYL lamina, benzylamine, phenethylamine, dialkylamino, trialkylamine, thiamine, aminopyrimidine, aminopyridine, purine, spermidine, alkylenediamine, glycinol, phenylglycinol, glycine, alanine, valine, leucine, isoleucine, norleucine, tyrosine, cystine, cysteine, methionine, Proline, hydroxyproline, histidine, ornithine, lysine, arginine, serine, threonine, phenylalanine, guanidine, substituted guanidine, ammonium, substituted ammonium and aluminium, educated (±)3-[6-[2-(2,3-dihydro-1,4-benzothiazin-4-Il)ethoxy]naphthyl]-2-ethoxypropanol acid;

any of the salts of Li, Na, K, CA, Mg, Fe, Cu, Zn, Mn, N,N'-diacetylethylenediamine, betaine, caffeine, 2-Diethylaminoethanol, 2-dimethylaminoethanol, N-ethylmorpholine, N-ethylpiperidine, glucamine, glucosamine, geranamine, Isopropylamine, methylglucamine, research, piperazine, piperidine, procaine, purines, theobromine, triethylamine, trimethylamine, Tripropylamine, tromethamine, diethanolamine, meglumine, Ethylenediamine, N,N'-diphenylethylenediamine, N,N'-dibenziletilendiaminom, N-benzylpenicillin, choline, kolingerova, dicyclohexylamine, benzylamine, phenethylamine, dialkylamino, trialkylamine, thiamine, aminopyrimidine, aminopyridine, purine, spermidine, alkylenediamine, glycinol, phenylglycinol, glycine, alanine, valine, leucine, isoleucine, norleucine, tyrosine, cystine, cysteine, m is thionine, Proline, hydroxyproline, histidine, ornithine, lysine, arginine, serine, threonine, phenylalanine, guanidine, substituted guanidine, ammonium, substituted ammonium and aluminium, educated (+)3-[6-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]naphthyl]-2-ethoxypropanol acid;

any of the salts of Li, Na, K, CA, Mg, Fe, Cu, Zn, Mn, N,N'-diacetylethylenediamine, betaine, caffeine, 2-Diethylaminoethanol, 2-dimethylaminoethanol, N-ethylmorpholine, N-ethylpiperidine, glucamine, glucosamine, geranamine, Isopropylamine, methylglucamine, research, piperazine, piperidine, procaine, purines, theobromine, triethylamine, trimethylamine, Tripropylamine, tromethamine, diethanolamine, meglumine, Ethylenediamine, N,N'-diphenylethylenediamine, N,N'-dibenziletilendiaminom, N-benzylpenicillin, choline, kolingerova, dicyclohexylamine, benzylamine, phenethylamine, dialkylamino, trialkylamine, thiamine, aminopyrimidine, aminopyridine, purine, spermidine, alkylenediamine, glycinol, phenylglycinol, glycine, alanine, valine, leucine, isoleucine, norleucine, tyrosine, cystine, cysteine, methionine, Proline, hydroxyproline, histidine, ornithine, lysine, arginine, serine, threonine, phenylalanine, guanidine, substituted guanidine, ammonium, substituted ammonium and aluminum formed (-)3-[6-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]naphthyl]-2-ethoxypropanol Ki is LOTOS;

any of the salts of Li, Na, K, CA, Mg, Fe, Cu, Zn, Mn, N,N'-diacetylethylenediamine, betaine, caffeine, 2-Diethylaminoethanol, 2-dimethylaminoethanol, N-ethylmorpholine, N-ethylpiperidine, glucamine, glucosamine, geranamine, Isopropylamine, methylglucamine, research, piperazine, piperidine, procaine, purines, theobromine, triethylamine, trimethylamine, Tripropylamine, tromethamine, diethanolamine, meglumine, Ethylenediamine, N,N'-diphenylethylenediamine, N,N'-dibenziletilendiaminom, N-benzylpenicillin, choline, kolingerova, dicyclohexylamine, benzylamine, phenethylamine, dialkylamino, trialkylamine, thiamine, aminopyrimidine, aminopyridine, purine, spermidine, alkylenediamine, glycinol, phenylglycinol, glycine, alanine, valine, leucine, isoleucine, norleucine, tyrosine, cystine, cysteine, methionine, Proline, hydroxyproline, histidine, ornithine, lysine, arginine, serine, threonine, phenylalanine, guanidine, substituted guanidine, ammonium, substituted ammonium and aluminium, educated (±)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-hydroxypropanoic acid;

any of the salts of Li, Na, K, CA, Mg, Fe, Cu, Zn, Mn, N,N'-diacetylethylenediamine, betaine, caffeine, 2-Diethylaminoethanol, 2-dimethylaminoethanol, N-ethylmorpholine, N-ethylpiperidine, glucamine, glucosamine, geranamine, Isopropylamine, methylglucamine, research, p is perazine, piperidine, procaine, purines, theobromine, triethylamine, trimethylamine, Tripropylamine, tromethamine, diethanolamine, meglumine, Ethylenediamine, N,N'-diphenylethylenediamine, N,N'-dibenziletilendiaminom, N-benzylpenicillin, choline, kolingerova, dicyclohexylamine, benzylamine, phenethylamine, dialkylamino, trialkylamine, thiamine, aminopyrimidine, aminopyridine, purine, spermidine, alkylenediamine, glycinol, phenylglycinol, glycine, alanine, valine, leucine, isoleucine, norleucine, tyrosine, cystine, cysteine, methionine, Proline, hydroxyproline, histidine, ornithine, lysine, arginine, serine, threonine, phenylalanine, guanidine, substituted guanidine, ammonium, substituted ammonium and aluminium, educated (+)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-hydroxypropanoic acid;

any of the salts of Li, Na, K, CA, Mg, Fe, Cu, Zn, Mn, N,N'-diacetylethylenediamine, betaine, caffeine, 2-Diethylaminoethanol, 2-dimethylaminoethanol, N-ethylmorpholine, N-ethylpiperidine, glucamine, glucosamine, geranamine, Isopropylamine, methylglucamine, research, piperazine, piperidine, procaine, purines, theobromine, triethylamine, trimethylamine, Tripropylamine, tromethamine, diethanolamine, meglumine, Ethylenediamine, N,N'-diphenylethylenediamine, N,N'-dibenziletilendiaminom, N-benzylpenicillin, choline, kolingerova, decollage is Ilumina, benzylamine, phenethylamine, dialkylamino, trialkylamine, thiamine, aminopyrimidine, aminopyridine, purine, spermidine, alkylenediamine, glycinol, phenylglycinol, glycine, alanine, valine, leucine, isoleucine, norleucine, tyrosine, cystine, cysteine, methionine, Proline, hydroxyproline, histidine, ornithine, lysine, arginine, serine, threonine, phenylalanine, guanidine, substituted guanidine, ammonium, substituted ammonium and aluminum formed (-)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-hydroxypropanoic acid;

any of the salts of Li, Na, K, CA, Mg, Fe, Cu, Zn, Mn, N,N'-diacetylethylenediamine, betaine, caffeine, 2-Diethylaminoethanol, 2-dimethylaminoethanol, N-ethylmorpholine, N-ethylpiperidine, glucamine, glucosamine, geranamine, Isopropylamine, methylglucamine, research, piperazine, piperidine, procaine, purines, theobromine, triethylamine, trimethylamine, Tripropylamine, tromethamine, diethanolamine, meglumine, Ethylenediamine, N,N'-diphenylethylenediamine, N,N'-dibenziletilendiaminom, N-benzylpenicillin, choline, kolingerova, dicyclohexylamine, benzylamine, phenethylamine, dialkylamino, trialkylamine, thiamine, aminopyrimidine, aminopyridine, purine, spermidine, alkylenediamine, glycinol, phenylglycinol, glycine, alanine, valine, leucine, isoleucine, norleucine, tyrosine, cystine, cysteine, METI the Nina, Proline, hydroxyproline, histidine, ornithine, lysine, arginine, serine, threonine, phenylalanine, guanidine, substituted guanidine, ammonium, substituted ammonium and aluminium, educated (±)3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-hydroxypropanoic acid;

any of the salts of Li, Na, K, CA, Mg, Fe, Cu, Zn, Mn, N,N'-diacetylethylenediamine, betaine, caffeine, 2-Diethylaminoethanol, 2-dimethylaminoethanol, N-ethylmorpholine, N-ethylpiperidine, glucamine, glucosamine, geranamine, Isopropylamine, methylglucamine, research, piperazine, piperidine, procaine, purines, theobromine, triethylamine, trimethylamine, Tripropylamine, tromethamine, diethanolamine, meglumine, Ethylenediamine, N,N'-diphenylethylenediamine, N,N'-dibenziletilendiaminom, N-benzylpenicillin, choline, kolingerova, dicyclohexylamine, benzylamine, phenethylamine, dialkylamino, trialkylamine, thiamine, aminopyrimidine, aminopyridine, purine, spermidine, alkylenediamine, glycinol, phenylglycinol, glycine, alanine, valine, leucine, isoleucine, norleucine, tyrosine, cystine, cysteine, methionine, Proline, hydroxyproline, histidine, ornithine, lysine, arginine, serine, threonine, phenylalanine, guanidine, substituted guanidine, ammonium, substituted ammonium and aluminium, educated (+)3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-hydroxypropane the second acid;

any of the salts of Li, Na, K, CA, Mg, Fe, Cu, Zn, Mn, N,N'-diacetylethylenediamine, betaine, caffeine, 2-Diethylaminoethanol, 2-dimethylaminoethanol, N-ethylmorpholine, N-ethylpiperidine, glucamine, glucosamine, geranamine, Isopropylamine, methylglucamine, research, piperazine, piperidine, procaine, purines, theobromine, triethylamine, trimethylamine, Tripropylamine, tromethamine, diethanolamine, meglumine, Ethylenediamine, N,N'-diphenylethylenediamine, N,N'-dibenziletilendiaminom, N-benzylpenicillin, choline, kolingerova, dicyclohexylamine, benzylamine, phenethylamine, dialkylamino, trialkylamine, thiamine, aminopyrimidine, aminopyridine, purine, spermidine, alkylenediamine, glycinol, phenylglycinol, glycine, alanine, valine, leucine, isoleucine, norleucine, tyrosine, cystine, cysteine, methionine, Proline, hydroxyproline, histidine, ornithine, lysine, arginine, serine, threonine, phenylalanine, guanidine, substituted guanidine, ammonium, substituted ammonium and aluminum formed (-)3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-hydroxypropanoic acid;

any of the salts of Li, Na, K, CA, Mg, Fe, Cu, Zn, Mn, N,N'-diacetylethylenediamine, betaine, caffeine, 2-Diethylaminoethanol, 2-dimethylaminoethanol, N-ethylmorpholine, N-ethylpiperidine, glucamine, glucosamine, geranamine, Isopropylamine, methylglucamine, research, Pieper is Zina, piperidine, procaine, purines, theobromine, triethylamine, trimethylamine, Tripropylamine, tromethamine, diethanolamine, meglumine, Ethylenediamine, N,N'-diphenylethylenediamine, N,N'-dibenziletilendiaminom, N-benzylpenicillin, choline, kolingerova, dicyclohexylamine, benzylamine, phenethylamine, dialkylamino, trialkylamine, thiamine, aminopyrimidine, aminopyridine, purine, spermidine, alkylenediamine, glycinol, phenylglycinol, glycine, alanine, valine, leucine, isoleucine, norleucine, tyrosine, cystine, cysteine, methionine, Proline, hydroxyproline, histidine, ornithine, lysine, arginine, serine, threonine, phenylalanine, guanidine, substituted guanidine, ammonium, substituted ammonium and aluminium, educated (±)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-benzyloxypropionic acid;

any of the salts of Li, Na, K, CA, Mg, Fe, Cu, Zn, Mn, N,N'-diacetylethylenediamine, betaine, caffeine, 2-Diethylaminoethanol, 2-dimethylaminoethanol, N-ethylmorpholine, N-ethylpiperidine, glucamine, glucosamine, geranamine, Isopropylamine, methylglucamine, research, piperazine, piperidine, procaine, purines, theobromine, triethylamine, trimethylamine, Tripropylamine, tromethamine, diethanolamine, meglumine, Ethylenediamine, N,N'-diphenylethylenediamine, N,N'-dibenziletilendiaminom, N-benzylpenicillin, choline, kolingerova, dice is legacylogin, benzylamine, phenethylamine, dialkylamino, trialkylamine, thiamine, aminopyrimidine, aminopyridine, purine, spermidine, alkylenediamine, glycinol, phenylglycinol, glycine, alanine, valine, leucine, isoleucine, norleucine, tyrosine, cystine, cysteine, methionine, Proline, hydroxyproline, histidine, ornithine, lysine, arginine, serine, threonine, phenylalanine, guanidine, substituted guanidine, ammonium, substituted ammonium and aluminium, educated (+)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-benzyloxypropionic acid;

any of the salts of Li, Na, K, CA, Mg, Fe, Cu, Zn, Mn, N,N'-diacetylethylenediamine, betaine, caffeine, 2-Diethylaminoethanol, 2-dimethylaminoethanol, N-ethylmorpholine, N-ethylpiperidine, glucamine, glucosamine, geranamine, Isopropylamine, methylglucamine, research, piperazine, piperidine, procaine, purines, theobromine, triethylamine, trimethylamine, Tripropylamine, tromethamine, diethanolamine, meglumine, Ethylenediamine, N,N'-diphenylethylenediamine, N,N'-dibenziletilendiaminom, N-benzylpenicillin, choline, kolingerova, dicyclohexylamine, benzylamine, phenethylamine, dialkylamino, trialkylamine, thiamine, aminopyrimidine, aminopyridine, purine, spermidine, alkylenediamine, glycinol, phenylglycinol, glycine, alanine, valine, leucine, isoleucine, norleucine, tyrosine, cystine, cysteine, IU the ionina, Proline, hydroxyproline, histidine, ornithine, lysine, arginine, serine, threonine, phenylalanine, guanidine, substituted guanidine, ammonium, substituted ammonium and aluminum formed (-)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-benzyloxypropionic acid;

any of the salts of Li, Na, K, CA, Mg, Fe, Cu, Zn, Mn, N,N'-diacetylethylenediamine, betaine, caffeine, 2-Diethylaminoethanol, 2-dimethylaminoethanol, N-ethylmorpholine, N-ethylpiperidine, glucamine, glucosamine, geranamine, Isopropylamine, methylglucamine, research, piperazine, piperidine, procaine, purines, theobromine, triethylamine, trimethylamine, Tripropylamine, tromethamine, diethanolamine, meglumine, Ethylenediamine, N,N'-diphenylethylenediamine, N,N'-dibenziletilendiaminom, N-benzylpenicillin, choline, kolingerova, dicyclohexylamine, benzylamine, phenethylamine, dialkylamino, trialkylamine, thiamine, aminopyrimidine, aminopyridine, purine, spermidine, alkylenediamine, glycinol, phenylglycinol, glycine, alanine, valine, leucine, isoleucine, norleucine, tyrosine, cystine, cysteine, methionine, Proline, hydroxyproline, histidine, ornithine, lysine, arginine, serine, threonine, phenylalanine, guanidine, substituted guanidine, ammonium, substituted ammonium and aluminium, educated (±)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-butoxypropan the howling acid;

any of the salts of Li, Na, K, CA, Mg, Fe, Cu, Zn, Mn, N,N'-diacetylethylenediamine, betaine, caffeine, 2-Diethylaminoethanol, 2-dimethylaminoethanol, N-ethylmorpholine, N-ethylpiperidine, glucamine, glucosamine, geranamine, Isopropylamine, methylglucamine, research, piperazine, piperidine, procaine, purines, theobromine, triethylamine, trimethylamine, Tripropylamine, tromethamine, diethanolamine, meglumine, Ethylenediamine, N,N'-diphenylethylenediamine, N,N'-dibenziletilendiaminom, N-benzylpenicillin, choline, kolingerova, dicyclohexylamine, benzylamine, phenethylamine, dialkylamino, trialkylamine, thiamine, aminopyrimidine, aminopyridine, purine, spermidine, alkylenediamine, glycinol, phenylglycinol, glycine, alanine, valine, leucine, isoleucine, norleucine, tyrosine, cystine, cysteine, methionine, Proline, hydroxyproline, histidine, ornithine, lysine, arginine, serine, threonine, phenylalanine, guanidine, substituted guanidine, ammonium, substituted ammonium and aluminium, educated (+)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-butoxypropan acid;

any of the salts of Li, Na, K, CA, Mg, Fe, Cu, Zn, Mn, N,N'-diacetylethylenediamine, betaine, caffeine, 2-Diethylaminoethanol, 2-dimethylaminoethanol, N-ethylmorpholine, N-ethylpiperidine, glucamine, glucosamine, geranamine, Isopropylamine, methylglucamine, the research, the Pipera the ina, piperidine, procaine, purines, theobromine, triethylamine, trimethylamine, Tripropylamine, tromethamine, diethanolamine, meglumine, Ethylenediamine, N,N'-diphenylethylenediamine, N,N'-dibenziletilendiaminom, N-benzylpenicillin, choline, kolingerova, dicyclohexylamine, benzylamine, phenethylamine, dialkylamino, trialkylamine, thiamine, aminopyrimidine, aminopyridine, purine, spermidine, alkylenediamine, glycinol, phenylglycinol, glycine, alanine, valine, leucine, isoleucine, norleucine, tyrosine, cystine, cysteine, methionine, Proline, hydroxyproline, histidine, ornithine, lysine, arginine, serine, threonine, phenylalanine, guanidine, substituted guanidine, ammonium, substituted ammonium and aluminum formed (-)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-butoxypropan acid;

any of the salts of Li, Na, K, CA, Mg, Fe, Cu, Zn, Mn, N,N'-diacetylethylenediamine, betaine, caffeine, 2-Diethylaminoethanol, 2-dimethylaminoethanol, N-ethylmorpholine, N-ethylpiperidine, glucamine, glucosamine, geranamine, Isopropylamine, methylglucamine, research, piperazine, piperidine, procaine, purines, theobromine, triethylamine, trimethylamine, Tripropylamine, tromethamine, diethanolamine, meglumine, Ethylenediamine, N,N'-diphenylethylenediamine, N,N'-dibenziletilendiaminom, N-benzylpenicillin, choline, kolingerova, DICYCLOHEXYL lamina, benzylamine, phenethylamine, dialkylamino, trialkylamine, thiamine, aminopyrimidine, aminopyridine, purine, spermidine, alkylenediamine, glycinol, phenylglycinol, glycine, alanine, valine, leucine, isoleucine, norleucine, tyrosine, cystine, cysteine, methionine, Proline, hydroxyproline, histidine, ornithine, lysine, arginine, serine, threonine, phenylalanine, guanidine, substituted guanidine, ammonium, substituted ammonium and aluminium, educated (±)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-Il)ethoxy]phenyl]-2-hexyloxyphenol acid;

any of the salts of Li, Na, K, CA, Mg, Fe, Cu, Zn, Mn, N,N'-diacetylethylenediamine, betaine, caffeine, 2-Diethylaminoethanol, 2-dimethylaminoethanol, N-ethylmorpholine, N-ethylpiperidine, glucamine, glucosamine, geranamine, Isopropylamine, methylglucamine, research, piperazine, piperidine, procaine, purines, theobromine, triethylamine, trimethylamine, Tripropylamine, tromethamine, diethanolamine, meglumine, Ethylenediamine, N,N'-diphenylethylenediamine, N,N'-dibenziletilendiaminom, N-benzylpenicillin, choline, kolingerova, dicyclohexylamine, benzylamine, phenethylamine, dialkylamino, trialkylamine, thiamine, aminopyrimidine, aminopyridine, purine, spermidine, alkylenediamine, glycinol, phenylglycinol, glycine, alanine, valine, leucine, isoleucine, norleucine, tyrosine, cystine, cysteine is, methionine, Proline, hydroxyproline, histidine, ornithine, lysine, arginine, serine, threonine, phenylalanine, guanidine, substituted guanidine, ammonium, substituted ammonium and aluminium, educated (+)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-hexyloxyphenol acid;

any of the salts of Li, Na, K, CA, Mg, Fe, Cu, Zn, Mn, N,N'-diacetylethylenediamine, betaine, caffeine, 2-Diethylaminoethanol, 2-dimethylaminoethanol, N-ethylmorpholine, N-ethylpiperidine, glucamine, glucosamine, geranamine, Isopropylamine, methylglucamine, research, piperazine, piperidine, procaine, purines, theobromine, triethylamine, trimethylamine, Tripropylamine, tromethamine, diethanolamine, meglumine, Ethylenediamine, N,N'-diphenylethylenediamine, N,N'-dibenziletilendiaminom, N-benzylpenicillin, choline, kolingerova, dicyclohexylamine, benzylamine, phenethylamine, dialkylamino, trialkylamine, thiamine, aminopyrimidine, aminopyridine, purine, spermidine, alkylenediamine, glycinol, phenylglycinol, glycine, alanine, valine, leucine, isoleucine, norleucine, tyrosine, cystine, cysteine, methionine, Proline, hydroxyproline, histidine, ornithine, lysine, arginine, serine, threonine, phenylalanine, guanidine, substituted guanidine, ammonium, substituted ammonium and aluminum formed (-)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-exile is eproposal acid;

any of the salts of Li, Na, K, CA, Mg, Fe, Cu, Zn, Mn, N,N'-diacetylethylenediamine, betaine, caffeine, 2-Diethylaminoethanol, 2-dimethylaminoethanol, N-ethylmorpholine, N-ethylpiperidine, glucamine, glucosamine, geranamine, Isopropylamine, methylglucamine, research, piperazine, piperidine, procaine, purines, theobromine, triethylamine, trimethylamine, Tripropylamine, tromethamine, diethanolamine, meglumine, Ethylenediamine, N,N'-diphenylethylenediamine, N,N'-dibenziletilendiaminom, N-benzylpenicillin, choline, kolingerova, dicyclohexylamine, benzylamine, phenethylamine, dialkylamino, trialkylamine, thiamine, aminopyrimidine, aminopyridine, purine, spermidine, alkylenediamine, glycinol, phenylglycinol, glycine, alanine, valine, leucine, isoleucine, norleucine, tyrosine, cystine, cysteine, methionine, Proline, hydroxyproline, histidine, ornithine, lysine, arginine, serine, threonine, phenylalanine, guanidine, substituted guanidine, ammonium, substituted ammonium and aluminium, educated (±)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-phenoxypropionic acid;

any of the salts of Li, Na, K, CA, Mg, Fe, Cu, Zn, Mn, N,N'-diacetylethylenediamine, betaine, caffeine, 2-Diethylaminoethanol, 2-dimethylaminoethanol, N-ethylmorpholine, N-ethylpiperidine, glucamine, glucosamine, geranamine, Isopropylamine, methylglucamine, the research, the PI is erazine, piperidine, procaine, purines, theobromine, triethylamine, trimethylamine, Tripropylamine, tromethamine, diethanolamine, meglumine, Ethylenediamine, N,N'-diphenylethylenediamine, N,N'-dibenziletilendiaminom, N-benzylpenicillin, choline, kolingerova, dicyclohexylamine, benzylamine, phenethylamine, dialkylamino, trialkylamine, thiamine, aminopyrimidine, aminopyridine, purine, spermidine, alkylenediamine, glycinol, phenylglycinol, glycine, alanine, valine, leucine, isoleucine, norleucine, tyrosine, cystine, cysteine, methionine, Proline, hydroxyproline, histidine, ornithine, lysine, arginine, serine, threonine, phenylalanine, guanidine, substituted guanidine, ammonium, substituted ammonium and aluminium, educated (+)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-phenoxypropionic acid;

any of the salts of Li, Na, K, CA, Mg, Fe, Cu, Zn, Mn, N,N'-diacetylethylenediamine, betaine, caffeine, 2-Diethylaminoethanol, 2-dimethylaminoethanol, N-ethylmorpholine, N-ethylpiperidine, glucamine, glucosamine, geranamine, Isopropylamine, methylglucamine, research, piperazine, piperidine, procaine, purines, theobromine, triethylamine, trimethylamine, Tripropylamine, tromethamine, diethanolamine, meglumine, Ethylenediamine, N,N'-diphenylethylenediamine, N,N'-dibenziletilendiaminom, N-benzylpenicillin, choline, kolingerova, DICYCLOHEXYL lamina, benzylamine, phenethylamine, dialkylamino, trialkylamine, thiamine, aminopyrimidine, aminopyridine, purine, spermidine, alkylenediamine, glycinol, phenylglycinol, glycine, alanine, valine, leucine, isoleucine, norleucine, tyrosine, cystine, cysteine, methionine, Proline, hydroxyproline, histidine, ornithine, lysine, arginine, serine, threonine, phenylalanine, guanidine, substituted guanidine, ammonium, substituted ammonium and aluminum formed (-)3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-phenoxypropionic acid;

any of the salts of Li, Na, K, CA, Mg, Fe, Cu, Zn, Mn, N,N'-diacetylethylenediamine, betaine, caffeine, 2-Diethylaminoethanol, 2-dimethylaminoethanol, N-ethylmorpholine, N-ethylpiperidine, glucamine, glucosamine, geranamine, Isopropylamine, methylglucamine, research, piperazine, piperidine, procaine, purines, theobromine, triethylamine, trimethylamine, Tripropylamine, tromethamine, diethanolamine, meglumine, Ethylenediamine, N,N'-diphenylethylenediamine, N,N'-dibenziletilendiaminom, N-benzylpenicillin, choline, kolingerova, dicyclohexylamine, benzylamine, phenethylamine, dialkylamino, trialkylamine, thiamine, aminopyrimidine, aminopyridine, purine, spermidine, alkylenediamine, glycinol, phenylglycinol, glycine, alanine, valine, leucine, isoleucine, norleucine, tyrosine, cystine, cysteine, metio the ina, Proline, hydroxyproline, histidine, ornithine, lysine, arginine, serine, threonine, phenylalanine, guanidine, substituted guanidine, ammonium, substituted ammonium and aluminium, educated (±)3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-phenoxypropionic acid;

any of the salts of Li, Na, K, CA, Mg, Fe, Cu, Zn, Mn, N,N'-diacetylethylenediamine, betaine, caffeine, 2-Diethylaminoethanol, 2-dimethylaminoethanol, N-ethylmorpholine, N-ethylpiperidine, glucamine, glucosamine, geranamine, Isopropylamine, methylglucamine, research, piperazine, piperidine, procaine, purines, theobromine, triethylamine, trimethylamine, Tripropylamine, tromethamine, diethanolamine, meglumine, Ethylenediamine, N,N'-diphenylethylenediamine, N,N'-dibenziletilendiaminom, N-benzylpenicillin, choline, kolingerova, dicyclohexylamine, benzylamine, phenethylamine, dialkylamino, trialkylamine, thiamine, aminopyrimidine, aminopyridine, purine, spermidine, alkylenediamine, glycinol, phenylglycinol, glycine, alanine, valine, leucine, isoleucine, norleucine, tyrosine, cystine, cysteine, methionine, Proline, hydroxyproline, histidine, ornithine, lysine, arginine, serine, threonine, phenylalanine, guanidine, substituted guanidine, ammonium, substituted ammonium and aluminium, educated (+)3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-phenoxypropanol the acid;

any of the salts of Li, Na, K, CA, Mg, Fe, Cu, Zn, Mn, N,N'-diacetylethylenediamine, betaine, caffeine, 2-Diethylaminoethanol, 2-dimethylaminoethanol, N-ethylmorpholine, N-ethylpiperidine, glucamine, glucosamine, geranamine, Isopropylamine, methylglucamine, research, piperazine, piperidine, procaine, purines, theobromine, triethylamine, trimethylamine, Tripropylamine, tromethamine, diethanolamine, meglumine, Ethylenediamine, N,N'-diphenylethylenediamine, N,N'-dibenziletilendiaminom, N-benzylpenicillin, choline, kolingerova, dicyclohexylamine, benzylamine, phenethylamine, dialkylamino, trialkylamine, thiamine, aminopyrimidine, aminopyridine, purine, spermidine, alkylenediamine, glycinol, phenylglycinol, glycine, alanine, valine, leucine, isoleucine, norleucine, tyrosine, cystine, cysteine, methionine, Proline, hydroxyproline, histidine, ornithine, lysine, arginine, serine, threonine, phenylalanine, guanidine, substituted guanidine, ammonium, substituted ammonium and aluminum formed (-)3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]phenyl]-2-phenoxypropionic acid;

any of the salts of Li, Na, K, CA, Mg, Fe, Cu, Zn, Mn, N,N'-diacetylethylenediamine, betaine, caffeine, 2-Diethylaminoethanol, 2-dimethylaminoethanol, N-ethylmorpholine, N-ethylpiperidine, glucamine, glucosamine, geranamine, Isopropylamine, methylglucamine, the research, the Pipera the ina, piperidine, procaine, purines, theobromine, triethylamine, trimethylamine, Tripropylamine, tromethamine, diethanolamine, meglumine, Ethylenediamine, N,N'-diphenylethylenediamine, N,N'-dibenziletilendiaminom, N-benzylpenicillin, choline, kolingerova, dicyclohexylamine, benzylamine, phenethylamine, dialkylamino, trialkylamine, thiamine, aminopyrimidine, aminopyridine, purine, spermidine, alkylenediamine, glycinol, phenylglycinol, glycine, alanine, valine, leucine, isoleucine, norleucine, tyrosine, cystine, cysteine, methionine, Proline, hydroxyproline, histidine, ornithine, lysine, arginine, serine, threonine, phenylalanine, guanidine, substituted guanidine, ammonium, substituted ammonium and aluminium, educated (±)2-methyl-3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]-phenyl]-2-phenoxypropionic acid;

any of the salts of Li, Na, K, CA, Mg, Fe, Cu, Zn, Mn, N,N'-diacetylethylenediamine, betaine, caffeine, 2-Diethylaminoethanol, 2-dimethylaminoethanol, N-ethylmorpholine, N-ethylpiperidine, glucamine, glucosamine, geranamine, Isopropylamine, methylglucamine, research, piperazine, piperidine, procaine, purines, theobromine, triethylamine, trimethylamine, Tripropylamine, tromethamine, diethanolamine, meglumine, Ethylenediamine, N,N'-diphenylethylenediamine, N,N'-dibenziletilendiaminom, N-benzylpenicillin, choline, kolingerova, is illogically, benzylamine, phenethylamine, dialkylamino, trialkylamine, thiamine, aminopyrimidine, aminopyridine, purine, spermidine, alkylenediamine, glycinol, phenylglycinol, glycine, alanine, valine, leucine, isoleucine, norleucine, tyrosine, cystine, cysteine, methionine, Proline, hydroxyproline, histidine, ornithine, lysine, arginine, serine, threonine, phenylalanine, guanidine, substituted guanidine, ammonium, substituted ammonium and aluminium, educated (+)-2-methyl-3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-Il)ethoxy]-phenyl]-2-phenoxypropionic acid;

any of the salts of Li, Na, K, CA, Mg, Fe, Cu, Zn, Mn, N,N'-diacetylethylenediamine, betaine, caffeine, 2-Diethylaminoethanol, 2-dimethylaminoethanol, N-ethylmorpholine, N-ethylpiperidine, glucamine, glucosamine, geranamine, Isopropylamine, methylglucamine, research, piperazine, piperidine, procaine, purines, theobromine, triethylamine, trimethylamine, Tripropylamine, tromethamine, diethanolamine, meglumine, Ethylenediamine, N,N'-diphenylethylenediamine, N,N'-dibenziletilendiaminom, N-benzylpenicillin, choline, kolingerova, dicyclohexylamine, benzylamine, phenethylamine, dialkylamino, trialkylamine, thiamine, aminopyrimidine, aminopyridine, purine, spermidine, alkylenediamine, glycinol, phenylglycinol, glycine, alanine, valine, leucine, isoleucine, norleucine, tyrosine, cystine, cysteine is, methionine, Proline, hydroxyproline, histidine, ornithine, lysine, arginine, serine, threonine, phenylalanine, guanidine, substituted guanidine, ammonium, substituted ammonium and aluminum formed (- )-2-methyl-3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]-phenyl]-2-phenoxypropionic acid;

any of the salts of Li, Na, K, CA, Mg, Fe, Cu, Zn, Mn, N,N'-diacetylethylenediamine, betaine, caffeine, 2-Diethylaminoethanol, 2-dimethylaminoethanol, N-ethylmorpholine, N-ethylpiperidine, glucamine, glucosamine, geranamine, Isopropylamine, methylglucamine, research, piperazine, piperidine, procaine, purines, theobromine, triethylamine, trimethylamine, Tripropylamine, tromethamine, diethanolamine, meglumine, Ethylenediamine, N,N'-diphenylethylenediamine, N,N'-dibenziletilendiaminom, N-benzylpenicillin, choline, kolingerova, dicyclohexylamine, benzylamine, phenethylamine, dialkylamino, trialkylamine, thiamine, aminopyrimidine, aminopyridine, purine, spermidine, alkylenediamine, glycinol, phenylglycinol, glycine, alanine, valine, leucine, isoleucine, norleucine, tyrosine, cystine, cysteine, methionine, Proline, hydroxyproline, histidine, ornithine, lysine, arginine, serine, threonine, phenylalanine, guanidine, substituted guanidine, ammonium, substituted ammonium and aluminium, educated (±)2-methyl-3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy-phenyl]-2-phenoxypropionic acid;

any of the salts of Li, Na, K, CA, Mg, Fe, Cu, Zn, Mn, N,N'-diacetylethylenediamine, betaine, caffeine, 2-Diethylaminoethanol, 2-dimethylaminoethanol, N-ethylmorpholine, N-ethylpiperidine, glucamine, glucosamine, geranamine, Isopropylamine, methylglucamine, research, piperazine, piperidine, procaine, purines, theobromine, triethylamine, trimethylamine, Tripropylamine, tromethamine, diethanolamine, meglumine, Ethylenediamine, N,N'-diphenylethylenediamine, N,N'-dibenziletilendiaminom, N-benzylpenicillin, choline, kolingerova, dicyclohexylamine, benzylamine, phenethylamine, dialkylamino, trialkylamine, thiamine, aminopyrimidine, aminopyridine, purine, spermidine, alkylenediamine, glycinol, phenylglycinol, glycine, alanine, valine, leucine, isoleucine, norleucine, tyrosine, cystine, cysteine, methionine, Proline, hydroxyproline, histidine, ornithine, lysine, arginine, serine, threonine, phenylalanine, guanidine, substituted guanidine, ammonium, substituted ammonium and aluminium, educated (+)-2-methyl-3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]-phenyl]-2-phenoxypropionic acid;

any of the salts of Li, Na, K, CA, Mg, Fe, Cu, Zn, Mn, N,N'-diacetylethylenediamine, betaine, caffeine, 2-Diethylaminoethanol, 2-dimethylaminoethanol, N-ethylmorpholine, N-ethylpiperidine, glucamine, glucosamine, geranamine, Isopropylamine, methylglucamine, research,piperazine, piperidine, procaine, purines, theobromine, triethylamine, trimethylamine, Tripropylamine, tromethamine, diethanolamine, meglumine, Ethylenediamine, N,N'-diphenylethylenediamine, N,N'-dibenziletilendiaminom, N-benzylpenicillin, choline, kolingerova, dicyclohexylamine, benzylamine, phenethylamine, dialkylamino, trialkylamine, thiamine, aminopyrimidine, aminopyridine, purine, spermidine, alkylenediamine, glycinol, phenylglycinol, glycine, alanine, valine, leucine, isoleucine, norleucine, tyrosine, cystine, cysteine, methionine, Proline, hydroxyproline, histidine, ornithine, lysine, arginine, serine, threonine, phenylalanine, guanidine, substituted guanidine, ammonium, substituted ammonium and aluminum formed (- )-2-methyl-3-[4-[2-(2,3-dihydro-1,4-benzothiazin-4-yl)ethoxy]-phenyl]-2-phenoxypropionic acid;

any of the salts of Li, Na, K, CA, Mg, Fe, Cu, Zn, Mn, N,N'-diacetylethylenediamine, betaine, caffeine, 2-Diethylaminoethanol, 2-dimethylaminoethanol, N-ethylmorpholine, N-ethylpiperidine, glucamine, glucosamine, geranamine, Isopropylamine, methylglucamine, research, piperazine, piperidine, procaine, purines, theobromine, triethylamine, trimethylamine, Tripropylamine, tromethamine, diethanolamine, meglumine, Ethylenediamine, N,N'-diphenylethylenediamine, N,N'-dibenziletilendiaminom, N-benzylpenicillin, choline, kolingerova, dice is legacylogin, benzylamine, phenethylamine, dialkylamino, trialkylamine, thiamine, aminopyrimidine, aminopyridine, purine, spermidine, alkylenediamine, glycinol, phenylglycinol, glycine, alanine, valine, leucine, isoleucine, norleucine, tyrosine, cystine, cysteine, methionine, Proline, hydroxyproline, histidine, ornithine, lysine, arginine, serine, threonine, phenylalanine, guanidine, substituted guanidine, ammonium, substituted ammonium and aluminium, educated (±)3-[4-(4-benzyl-3,4-dihydro-2H-1,4-benzoxazin-2-yl)methoxyphenyl]-2-ethoxypropanol acid;

any of the salts of Li, Na, K, CA, Mg, Fe, Cu, Zn, Mn, N,N'-diacetylethylenediamine, betaine, caffeine, 2-Diethylaminoethanol, 2-dimethylaminoethanol, N-ethylmorpholine, N-ethylpiperidine, glucamine, glucosamine, geranamine, Isopropylamine, methylglucamine, research, piperazine, piperidine, procaine, purines, theobromine, triethylamine, trimethylamine, Tripropylamine, tromethamine, diethanolamine, meglumine, Ethylenediamine, N,N'-diphenylethylenediamine, N,N'-dibenziletilendiaminom, N-benzylpenicillin, choline, kolingerova, dicyclohexylamine, benzylamine, phenethylamine, dialkylamino, trialkylamine, thiamine, aminopyrimidine, aminopyridine, purine, spermidine, alkylenediamine, glycinol, phenylglycinol, glycine, alanine, valine, leucine, isoleucine, norleucine, tyrosine, cysteine, Cys is Aina, methionine, Proline, hydroxyproline, histidine, ornithine, lysine, arginine, serine, threonine, phenylalanine, guanidine, substituted guanidine, ammonium, substituted ammonium and aluminium, educated (+)3-[4-(4-benzyl-3,4-dihydro-2H-1,4-benzoxazin-2-yl)methoxyphenyl]-2-ethoxypropanol acid;

any of the salts of Li, Na, K, CA, Mg, Fe, Cu, Zn, Mn, N,N'-diacetylethylenediamine, betaine, caffeine, 2-Diethylaminoethanol, 2-dimethylaminoethanol, N-ethylmorpholine, N-ethylpiperidine, glucamine, glucosamine, geranamine, Isopropylamine, methylglucamine, research, piperazine, piperidine, procaine, purines, theobromine, triethylamine, trimethylamine, Tripropylamine, tromethamine, diethanolamine, meglumine, Ethylenediamine, N,N'-diphenylethylenediamine, N,N'-dibenziletilendiaminom, N-benzylpenicillin, choline, kolingerova, dicyclohexylamine, benzylamine, phenethylamine, dialkylamino, trialkylamine, thiamine, aminopyrimidine, aminopyridine, purine, spermidine, alkylenediamine, glycinol, phenylglycinol, glycine, alanine, valine, leucine, isoleucine, norleucine, tyrosine, cystine, pestaina, methionine, Proline, hydroxyproline, histidine, ornithine, lysine, arginine, serine, threonine, phenylalanine, guanidine, substituted guanidine, ammonium, substituted ammonium, and aluminum formed (-)3-[4-(4-benzyl-3,4-dihydro-2H-1,4-benzoxazin-2-yl)methoxy is enyl]-2-oxopropanoic acid.

17. Pharmaceutical composition having the property agonist of PPARα and PPARγcomprising the compound of formula (I) according to any one of claims 1,14 or 16, as well as pharmaceutically acceptable carrier, diluent, filler or MES.

18. Pharmaceutical composition comprising a compound of formula (I) according to any one of claims 1, 14 or 16, as well as inhibitors of HMG:CoA-reductase inhibitors, fibrates, nicotinic acid, cholestyramine, colestipol or probucol or their combination, together with a pharmaceutically acceptable carrier, diluent, filler or MES.

19. Pharmaceutical composition for 17 or 18 in the form of tablets, capsules, powder, syrup or suspension.

20. Pharmaceutical composition for 17 or 18 for the treatment and/or prevention of type II diabetes, intolerance to glucose, resistance to leptin, dyslipidemia, disorders related to syndrome X such as hypertension, obesity, insulin resistance, atherosclerosis, hyperlipidemia, coronary heart disease, glomerulosclerosis, psoriasis, xanthomas or cancer.

21. A method of prophylaxis or treatment of hypercholesterolemia and obesity that have a positive effect on hyperlipemia, hyperglycemia, obesity, intolerance to glucose, insulin resistance and those diseases in which the main pathophysiological mechanism is resistance to insulin, including the surrounding introduction to the needy in this patient, the compounds of formula (I) according to any one of claims 1, 11-13 or connection 14 or 16 or pharmaceutical composition of 17 or 18.

22. The method according to item 21, in which the disease is type II diabetes, impaired glucose tolerance, dyslipidemia, diseases related to syndrome X such as hypertension, obesity, insulin resistance, atherosclerosis, hyperlipidemia, coronary heart disease, glomerular sclerosis, psoriasis, xanthoma or cancer.

23. The method according to item 21 for the prevention and/or treatment of diseases associated with syndrome X, including the introduction of the needy in this patient agonist of PPARα and/or PPARγ, of the formula (I) according to any one of claims 1, 11-13 or connection 14 or 16 or pharmaceutical composition of 17 or 18.

24. The way to reduce total cholesterol, body weight, glucose levels, triglycerides, LDL, lonp and free fatty acids in blood plasma, including the introduction of the needy in this patient, the compounds of formula (I) according to any one of claims 1, 11-13 or connection 14 or 16 or pharmaceutical composition of 17 or 18.

25. The method of prevention or treatment of hyperlipemia, hypercholesterolemia, hyperglycemia, obesity, intolerance to glucose, resistance to leptin, resistance to insulin, or diseases in which the main pathophysiological mechanism is resistance to insulin, including introduction to the needy in this patient effective to the icesta the compounds of formula (I), defined in any one of claims 1, 11-13 or connection 14 or 16 or pharmaceutical compositions for 17 or 18 combined/simultaneously with inhibitors of HMG:COA-reductase inhibitors, fibrates, nicotinic acid, cholestyramine, colestipol or probucol or their combination in such a period of time, so they had a synergistic effect.

26. The method according A.25, in which the disease is type II diabetes, impaired glucose tolerance, dyslipidemia, diseases related to syndrome X such as hypertension, obesity, atherosclerosis, hyperlipidemia, coronary heart disease, glomerular sclerosis, psoriasis, xanthoma and cancer.

27. The method according A.25, for the treatment and/or prevention of diseases associated with syndrome X, including the introduction of the needy in this patient agonist of PPARα and/or PPARγ, of the formula (I) according to any one of claims 1, 11-13 or connection 14 or 16 or pharmaceutical compositions for 17 or 18 together with inhibitors of HMG:COA-reductase inhibitors, fibrates, nicotinic acid, cholestyramine, colestipol or probucol or their combination in such a period of time, so they had a synergistic effect.

28. The way to reduce the level of glucose, triglycerides, total cholesterol, LDL, lonp and free fatty acids in blood plasma, including the introduction of the needy in this patient, the compounds of formula (I) according to any one of claims 1 11-13 or connection 14 or 16 or pharmaceutical compositions for 17 or 18 combined/simultaneously with inhibitors of HMG:COA-reductase, fibrates, nicotinic acid, cholestyramine, colestipol or probucol that you can enter together or within such a period of time, so they had a synergistic effect.

29. The compound of formula (I) according to any one of claims 1, 11-13 or connection 14 or 16 for the prophylaxis or treatment of hyperlipidemia, hypercholesterolemia, hyperglycemia, obesity, intolerance to glucose, resistance to leptin, resistance to insulin, or diseases in which the main pathophysiological mechanism is resistance to insulin.

30. The compound of formula (I) according to any one of claims 1, 11-13 or connection 14 or 16 for the prevention or treatment of diseases such as type II diabetes, impaired glucose tolerance, dyslipidemia, disorders related to syndrome X such as hypertension, obesity, atherosclerosis, hyperlipidemia, coronary heart disease, glomerulosclerosis, psoriasis, xanthomas and cancer.

31. The compound of formula (I) according to any one of claims 1, 11-13 or connection 14 or 16 to reduce the level of glucose, triglycerides, total cholesterol, LDL, lonp and free fatty acids in plasma.

32. The compound of formula (I) according to any one of claims 1, 11-13 or connection 14 or 16 combined/simultaneously with inhibitors of HMG:COA-reductase inhibitors, fibrates, nicotinic acid, cholestyramine, colestipol or probucol to the E. you can enter the needy in this patient together or within such a period of time, so they had a synergistic effect for the prevention or treatment of hyperlipidemia, hypercholesterolemia, hyperglycemia, obesity, intolerance to glucose, resistance to leptin, resistance to insulin, or diseases in which the main pathophysiological mechanism is resistance to insulin.

33. The compound of formula (I) according to any one of claims 1, 11-13 or connection 14 or 16 combined/simultaneously with inhibitors of HMG:CoA-reductase inhibitors, fibrates, nicotinic acid, cholestyramine, colestipol or probucol that you can enter to the needy in this patient together or within such a period of time, so they had a synergistic effect for the prevention or treatment of diseases such as type II diabetes, impaired glucose tolerance, dyslipidemia, disorders related to syndrome X such as hypertension, obesity, atherosclerosis, hyperlipidemia, coronary heart disease, glomerulosclerosis, psoriasis, xanthomas and cancer.

34. The compound of formula (I) according to any one of claims 1, 11-13 or connection 14 or 16 combined/simultaneously with inhibitors of HMG:COA-reductase inhibitors, fibrates, nicotinic acid, cholestyramine, colestipol or probucol to reduce the level of glucose, triglycerides, total cholesterol, LDL, lonp or free fatty acids in plasma.

35. The connection form is s (I) according to any one of claims 1, 11-13 or connection 14 or 16 for the manufacture of medicaments intended for the prevention or treatment of hyperlipidemia, hypercholesterolemia, hyperglycemia, obesity, intolerance to glucose, resistance to leptin, resistance to insulin, or diseases in which the main pathophysiological mechanism is resistance to insulin.

36. The compound of formula (I) according to any one of claims 1, 11-13 or connection 14 or 16 for the manufacture of medicaments intended for the prevention or treatment of such diseases as type II diabetes, impaired glucose tolerance, dyslipidemia, disorders related to syndrome X such as hypertension, obesity, atherosclerosis, hyperlipidemia, coronary heart disease, glomerulosclerosis, psoriasis, xanthomas and cancer.

37. The compound of formula (I) according to any one of claims 1, 11-13 or connection 14 or 16 for the manufacture of drugs intended to reduce the level of glucose, triglycerides, total cholesterol, LDL, lonp or free fatty acids in plasma.

38. The compounds of formula (I) according to any one of claims 1, 11-13 or connection 14 or 16 for the manufacture of drugs in combination with inhibitors of HMG:COA-reductase inhibitors, fibrates, nicotinic acid, cholestyramine, colestipol or probucol intended for the prevention or treatment of hyperlipemia, hypercholesterinemia is, hyperglycemia, obesity, intolerance to glucose, resistance to leptin, resistance to insulin, or diseases in which the main pathophysiological mechanism is resistance to insulin.

39. The compound of formula (I) according to any one of claims 1, 11-13 or connection 14 or 16 for the manufacture of drugs in combination with inhibitors of HMG:COA-reductase inhibitors, fibrates, nicotinic acid, cholestyramine, colestipol or probucol intended for the prevention or treatment of such diseases as type II diabetes, impaired glucose tolerance, dyslipidemia, disorders related to syndrome X such as hypertension, obesity, atherosclerosis, hyperlipidemia, coronary heart disease, glomerulosclerosis, psoriasis, xanthomas and cancer.

40. The compound of formula (I) according to any one of claims 1, 11-13 or connection 14 or 16 for the manufacture of drugs in combination with inhibitors of HMG:COA-reductase inhibitors, fibrates, nicotinic acid, cholestyramine, colestipol or probucol intended to reduce the level of glucose, triglycerides, total cholesterol, LDL, lonp or free fatty acids in plasma.

41. Pharmaceutical composition for 17 or 18, intended for the prevention or treatment of hyperlipidemia, hypercholesterolemia, hyperglycemia, obesity, intolerance to glucose, resistance to late is, resistance to insulin or diseases in which the main pathophysiological mechanism is resistance to insulin.

42. Pharmaceutical composition for 17 or 18, intended for the prevention or treatment of diseases such as type II diabetes, intolerance to glucose, dyslipidemia, disorders related to syndrome X such as hypertension, obesity, atherosclerosis, hyperlipidemia, coronary heart disease, glomerulosclerosis, psoriasis, xanthomas or cancer.

43. Pharmaceutical composition for 17 or 18, which is intended to reduce the level of glucose, triglycerides, total cholesterol, LDL, lonp or free fatty acids in plasma.

44. Pharmaceutical composition for 17 or 18 for the manufacture of drugs in combination with inhibitors of HMG:COA-reductase inhibitors, fibrates, nicotinic acid, cholestyramine, colestipol or probucol intended for the prevention or treatment of hyperlipemia, hypercholesterolemia, hyperglycemia, osteoporosis, obesity, intolerance to glucose, resistance to leptin, resistance to insulin, or diseases in which the main pathophysiological mechanism is resistance to insulin.

45. Pharmaceutical composition for 17 or 18 combined/simultaneously with inhibitors of HMG:COA-reductase inhibitors, fibrates, nicotinic acid, holisti is an amine, colestipol or probucol that you can enter to the needy in this patient together or within such a period of time, so they had a synergistic effect, for the prevention or treatment of such diseases as type II diabetes, impaired glucose tolerance, dyslipidemia, disorders related to syndrome X such as hypertension, obesity, atherosclerosis, hyperlipidemia, coronary heart disease, glomerulosclerosis, psoriasis, xanthomas and cancer.

46. Pharmaceutical composition for 17 or 18 combined/simultaneously with inhibitors of HMG:COA-reductase inhibitors, fibrates, nicotinic acid, cholestyramine, colestipol or probucol to reduce the level of glucose, triglycerides, total cholesterol, LDL, lonp or free fatty acids in plasma.

47. Pharmaceutical composition for 17 or 18 for the manufacture of medicaments intended for the prevention or treatment of hyperlipidemia, hypercholesterolemia, hyperglycemia, osteoporosis, obesity, intolerance to glucose, resistance to leptin, resistance to insulin, or diseases in which the main pathophysiological mechanism is resistance to insulin.

48. Pharmaceutical composition for 17 or 18 for the manufacture of medicaments intended for the prevention or treatment of such diseases as type II diabetes, impaired t is lerotholi to glucose, dyslipidemia, disorders related to syndrome X such as hypertension, obesity, atherosclerosis, hyperlipidemia, coronary heart disease, glomerulosclerosis, psoriasis, xanthomas and cancer.

49. Pharmaceutical composition for 17 or 18 for the manufacture of drugs intended to reduce the level of glucose, triglycerides, total cholesterol, LDL, lonp or free fatty acids in plasma.

50. Pharmaceutical composition for 17 or 18 for the manufacture of drugs in combination with inhibitors of HMG:COA-reductase inhibitors, fibrates, nicotinic acid, cholestyramine, colestipol or probucol intended for the prevention or treatment of such diseases as type II diabetes, impaired glucose tolerance, dyslipidemia, disorders related to syndrome X such as hypertension, obesity, atherosclerosis, hyperlipidemia, coronary heart disease, glomerulosclerosis, psoriasis, xanthomas and cancer.

51. Pharmaceutical composition for 17 or 18 for the manufacture of drugs in combination with inhibitors of HMG:COA-reductase inhibitors, fibrates, nicotinic acid, cholestyramine, colestipol or probucol intended for lowering levels of glucose, triglycerides, total cholesterol, LDL, lonp or free fatty acids in plasma.

52. The method of obtaining the compounds of formula (I)

its tautomeric forms, stereoisomers, polymorphic forms, pharmaceutically acceptable salts, pharmaceutically acceptable solvate, where the group R1, R2, R3, R4group and R5and R6when they are connected to carbon atoms, represent hydrogen, halogen, hydroxy, alkyl, alkoxy; R5and R6one, or both, can also be oxoprop when they are linked to the carbon atom; when R5and R6linked to the nitrogen atom, they represent a hydrogen, hydroxy or unsubstituted group selected from alkyl, alkoxy, aralkyl; x is the heteroatom selected from oxygen or sulfur; Ar denotes unsubstituted divalent phenylene, naftilan or benzofuran; R7means a hydrogen atom, alkoxy, lower alkyl or forms a bond with a neighboring group, R8; R8means hydrogen, lower alkyl, unsubstituted or substituted aralkyl, or forms a bond with R7; R9means hydrogen or unsubstituted group selected from alkyl, aryl; R10means hydrogen; Y represents oxygen or NR12where R12means hydrogen, alkyl; n is an integer from 1 to 4; m is an integer 1, including the hydrolysis of compounds of formula (I), where R10means unsubstituted group selected from alkyl, aryl; R1, R2, R3, R4, R5, R6 , R7, R8, R9, Ar, X, n and m have the above values.



 

Same patents:

FIELD: organic chemistry, medicine, hematology.

SUBSTANCE: invention elates to new compounds that inhibit activated blood coagulating factor X (Fxa factor) eliciting the strong anti-coagulating effect. Invention proposes compound of the formula (1): Q1-Q2-C(=C)-N-(R1)-Q3-N(R2)-T1-Q4(1) wherein R1, R2, Q1, Q2, Q4 and T1 have corresponding values, and Q2 represents the group of the formula: wherein R9, R10 and Q5 have corresponding values also, or its salt, solvate or N-oxide. Invention provides the development of a novel compound possessing strong Fxa-inhibiting effect and showing the rapid, significant and stable anti-thrombosis effectin oral administration.

EFFECT: valuable medicinal properties of compounds.

13 cl, 1 tbl, 195 ex

FIELD: organic chemistry, pharmacy.

SUBSTANCE: invention relates to compounds of the general formula (I) and pharmaceutical composition based on thereof possessing properties of ligand binding with adenosine receptors selectively. Invention provides preparing new compounds possessing useful biological properties.

EFFECT: valuable properties of compounds.

6 cl, 375 ex

FIELD: organic chemistry, chemical technology, medicine, pharmacy.

SUBSTANCE: invention relates to new derivatives of 4-aminopiptidine of the general formula (I): wherein R1 means (C1-C6)-alkyl, -(CH2)m-Y-Z11 or -(CH2)m-Z12 wherein Z11 means (C1-C6)-alkyl; Z12 means bis-phenyl, (C3-C7)-cycloalkyl, (C3-C7)-heterocycloalkyl with 1 or 2 heteroatoms taken among nitrogen (N) or oxygen (O) atoms, possibly substituted phenyl, naphthyl, possibly substituted (C5-C9)-heteroaryl wherein heteroatoms are taken among N; or Z12 means ; Y means O; or R1 means ; R2 means -C(Y)-NHX1, -C(O)X2 or -SO2X3; R3 means hydrogen atom (H), (C1-C4)-alkyl, (C2-C4)-alkenyl, possibly substituted heteroarylalkyl or -C(Y)-NHX1, -(CH2)n-C(O)X2 or -SO2X3 wherein X1-X3 have different values. Also, invention describes methods for preparing indicated substances by synthesis in liquid and solid phase. These compounds possessing good affinity to definite subtypes of somatostatin receptors can be used in treatment of pathological states or diseases caused by one or some somatostatin receptors.

EFFECT: improved preparing method, valuable medicinal properties of compounds.

14 cl, 4 tbl, 778 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new derivatives of isoquinoline carboxamide of the formula (I):

and to their pharmaceutically acceptable salts wherein R1 means hydrogen atom, hydroxy-group or -NHR2 wherein R2 means alkyl, arylalkyl, heterocyclylalkyl that comprises one or some heteroatoms taken among nitrogen, oxygen and sulfur atoms, cycloalkyl, alkylcarbonyl, cycloalkylcarbonyl, arylcarbonyl, heterocyclylcarbonyl that comprises one or some heteroatoms taken among nitrogen, oxygen and sulfur atoms, arylalkylcarbonyl, heterocyclylalkylcarbonyl that comprises one or some heteroatoms taken among nitrogen and oxygen atoms, alkyloxycarbonyl, arylalkyloxycarbonyl, heterocyclylalkyloxycarbonyl that comprises one or some heteroatoms taken among nitrogen atom, heterocyclyl that comprises one or some heteroatoms taken among nitrogen and sulfur atoms, alkylsulfonyl, arylsulfonyl or the group of the formula:

R3 and R4 mean alkyl independently of one another; R5 means alkyl; or R4 and R5 in common with carbon and sulfur atoms to which they are bound form a heterocycle; R6 means alkyl; R13 means hydrogen atom or the group of the formula:

R15 means aryl under condition that if R3, R4 and R5 form methyl, R6 forms tert.-butyl then R13 means hydrogen atom, and if R15 means phenyl then R2 doesn't mean benzyloxycarbonyl and 2-quinoline carbonyl (other values of radicals are given in cl. 1 of the invention claim). Also, invention relates to a medicinal agent based on these compounds used in treatment of HIV-mediated diseases. Invention provides preparing new compounds and a medicinal agent based on thereof in aims for treatment of HIV-mediated diseases.

EFFECT: valuable medicinal properties of compounds and medicinal agent.

14 cl, 11 tbl, 173 ex

FIELD: organic chemistry, herbicides, agriculture.

SUBSTANCE: invention elates to novel derivatives of uracil of the formula [I] possessing herbicide activity, a herbicide composition based on thereof and to a method for control of weeds. In derivatives of uracil of the formula [I] the group Q-R3 represents a substituted group taken among:

wherein a heterocyclic ring can be substituted with at least a substitute of a single species taken among the group involving halogen atom, (C1-C6)-alkyl-(C1-C6)-alkoxy; Y represents oxygen, sulfur atom, imino-group or (C1-C3)-alkylimino-group; R1 represents (C1-C3)-halogenalkyl; R2 represents (C1-C3)-alkyl; R3 represents OR7, SR8 or N(R9)R10; X1 represents halogen atom, cyano-group, thiocarbamoyl or nitro-group; X2 represents hydrogen or halogen atom wherein each among R7, R8 and R10 represents independently carboxy-(C1-C6)-alkyl and other substitutes given in the invention claim; R9 represents hydrogen atom or (C1-C6)-alkyl. Also, invention relates to intermediate compounds used in preparing uracil derivatives.

EFFECT: improved preparing method, valuable properties of compounds.

40 cl, 16 sch, 12 tbl, 65 ex

FIELD: pharmaceutical chemistry, medicine.

SUBSTANCE: invention relates to substituted pyridines and pyridazines with angiogenesis inhibition activity of general formula I

(I)1, wherein ring containing A, B, D, E, and L represents phenyl or nitrogen-containing heterocycle; X and Y are various linkage groups; R1 and R2 are identical or different and represent specific substituents or together form linkage ring; ring J represents aryl, pyridyl or cycloalkyl; and G's represent various specific substituents. Also disclosed are pharmaceutical composition containing claimed compounds, as well as method for treating of mammalian with abnormal angiogenesis or treating of increased penetrability using the same.

EFFECT: new pyridine and pyridazine derivatives with angiogenesis inhibition activity.

26 cl, 6 tbl, 114 ex

FIELD: organic chemistry, chemical technology, medicine.

SUBSTANCE: invention relates to a method for preparing derivatives of indole of the general formula (I):

wherein R1 represents hydroxy-group; R2 represents hydrogen atom, (C1-C6)-alkyl, (C1-C6)-alkoxy-group, (C2-C6)-alkoxyalkyl or 4-methoxybenzyl; R3 represents hydrogen atom or (C1-C6)-alkyl; each among R4 and R represents independently hydrogen atom, (C1-C6)-alkyl or (C1-C6)-alkoxy-group; D represents an ordinary bond, (C1-C6)-alkylene, (C2-C6)-alkenylene or (C1-C6)-oxyalkylene; in the group-G-R6 wherein G represents an ordinary bond, (C1-C6)-alkylene; R represents saturated or unsaturated carbocyclic ring (C3-C15) or 4-15-membered heterocyclic ring comprising 1-5 atoms of nitrogen, sulfur and/or oxygen wherein this ring can be substituted. Also, invention describes a method for preparing derivatives of indole and DP-receptor antagonist comprising derivative of the formula (I) as an active component. As far as compounds of the formula (I) bind with DP-receptors and they are antagonists of DP-receptors then they can be useful for prophylaxis and/or treatment of diseases, for example, allergic diseases.

EFFECT: improved preparing method, valuable medicinal properties of compounds.

11 cl, 7 tbl, 353 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to biologically active compounds, in particular, to substituted 5R1,6R2-thiadiazine-2-amines and pharmaceutical compositions comprising thereof that can be used in medicine as potential pharmacologically active substances eliciting the unique combination of properties: expressed anticoagulant activity in combination with capacity to inhibit aggregation of platelets. Effect of these substances differ from preparations used in medicinal practice and they can be used therefore in treatment of such diseases as myocardium infarction, disturbance in cerebral circulation, rejection of transplanted organs and tissues and so on. Indicated compounds correspond to the formula (I):

wherein values of radicals R1, R2 and R3 are given in the invention claim.

EFFECT: valuable medicinal properties of compounds.

4 cl, 2 tbl, 7 dwg, 33 ex

FIELD: organic chemistry, pesticides, agriculture.

SUBSTANCE: invention relates to compounds that elicit high pesticide activity and can be used in control of pests of domestic and agricultural animals. Indicated compounds show the formula (I):

wherein R1 means halogen atom, (C1-C6)-halogenalkyl; R2 means hydrogen atom (H), (C1-C6)-alkyl, (C1-C6)-alkylene-phenyl; X1 means nitrogen atom (N); X2 means group C(CN); X3 means oxygen atom (O); Q means CH; R3 and R4 mean independently of one another hydrogen atom (H) or in common with carbon atom with which they are bound form (C3-C7)-cycloalkyl ring; R5 means a substitute taken among group including (C1-C6)-halogenalkyl, halogen atom being if m above 1 then substitutes R5 can be similar or different; m = 1, 2 or 3; n = 0 or 1. Also, invention describes a method for their preparing and method for control of pests.

EFFECT: valuable pesticide properties of compounds.

7 cl, 3 tbl, 14 ex

FIELD: organic chemistry, chemical technology, agriculture.

SUBSTANCE: invention describes substituted azadioxocycloalkenes of the general formula (I): wherein A means unsubstituted or methyl-substituted dimethylene; Ar means unsubstituted or fluorine-substituted ortho-phenylene, thiophendiyl or pyridindiyl; E means group of the formula: wherein G means oxygen atom, groups -O-CH2-, -CH2-O- or -C(CH3)=N-O-CH2-; Z means unsubstituted or substituted phenyl, pyrimidinyl or thiadiazolyl, or naphthyl. Invention describes 4 methods for preparing compounds of the formula (I), 5 species of intermediate compounds used for preparing compounds of the formula (I), fungicide agents comprising compound of the formula (I) as an active substance, a method for preparing fungicide agents, method for control of harmful fungi using compound of the formula (I). Compounds of the formula (I) show fungicide properties and therefore they can be used in agriculture.

EFFECT: improved preparing methods, valuable properties of compounds.

13 cl, 5 tbl, 18 ex

FIELD: organic chemistry, medicine, oncology, pharmacy.

SUBSTANCE: invention relates to quinazoline derivatives of the formula (I) or their pharmaceutically acceptable salts wherein m = 0 or 1; each group R1 can be similar or different and represents halogen atom, hydroxy- and (C1-C6)-alkoxy-group, or group of the formula Q3-X1 wherein X1 represents oxygen atom (O); Q3 represents phenyl-(C1-C6)-alkyl, heteroaryl-(C1-C6)-alkyl, heterocyclyl or heterocyclyl-(C1-C6)-alkyl, and wherein heteroaryl group represents aromatic 5- or 6-membered monocyclic rings with one or two nitrogen heteroatoms, and any heterocyclyl group defined as the group R1 represents non-aromatic saturated or partially saturated 3-6-membered monocyclic ring with one or two heteroatoms chosen from oxygen and nitrogen atoms, and wherein adjacent carbon atoms in any (C2-C6)-alkylene chain in the substitute R1 are separated optionally by incorporation of oxygen atom (O) in the chain, and wherein any group CH2 or CH3 in the substitute R1 comprises optionally in each of indicated groups CH2 or CH3 one or some halogen substitutes or a substitute chosen from hydroxy-, (C1-C6)-alkoxy-group, (C1-C6)-alkylsulfonyl or pyridyloxy-group, and wherein any heteroaryl or heterocyclyl group in the substitute R1 comprises optionally 1, 2 or 3 substitutes that can be similar or different and chosen from hydroxy-group, carbamoyl, (C1-C6)-alkyl, (C1-C6)-alkoxycarbonyl, N-(C1-C6)-alkylcarbamoyl, N,N-di-[(C1-C6)-alkyl]-carbamoyl, (C1-C6)-alkoxy-(C1-C6)-alkyl and cyano-(C1-C6)-alkyl, or among group of the formula -X5-Q6 wherein X5 represents a direct bond or -CO, and Q6 represents heterocyclyl or heterocyclyl-(C1-C6)-alkyl that comprises optionally (C1-C6)-alkyl as a substitute wherein heterocyclyl group represents non-aromatic, fully or partially saturated 5- or 6-membered monocyclic ring with one or two heteroatoms chosen from nitrogen and oxygen atom; R2 represents hydrogen atom; R3 represents hydrogen atom; Z represents a direct bond or oxygen atom; Q1 represents phenyl, (C3-C7)-cycloalkyl, heteroaryl-(C1-C6)-alkyl, heterocyclyl or heterocyclyl-(C1-C6)-alkyl wherein heteroaryl group represents 5- or 6-membered aromatic monocyclic ring with I, 2 or 3 heteroatoms of nitrogen, and any heterocyclyl group represents non-aromatic fully or partially saturated 5- or 6-membered monocyclic ring with one or two heteroatoms chosen from oxygen, nitrogen or sulfur atom, or when Z represents oxygen atom (O) then Q1 can represent (C1-C6)-alkyl or (C1-C6)-alkoxy-(C1-C6)-alkyl and wherein any heterocyclyl group in the group -Q1-Z- comprises substitutes chosen from (C1-C6)-alkyl, (C1-C)-alkoxycarbonyl and pyridylmethyl, and wherein any heterocyclyl group in the group -Q1-Z- comprises optionally 1 or 2 oxo-substitutes; Q2 represents aryl group of the formula (Ia): wherein G1 represents halogen atom, trifluoromethyl, (C1-C6)-alkyl, (C2-C8)-alkenyl, (C2-C8)-alkynyl, (C1-C6)-alkoxy-, (C1-C6)-alkylthio-group, (C2-C6)-alkanoyl, pyrrolyl, pyrrolidinyl, piperidinyl and morpholinomethyl, and each G2, G3, G4 and G5 that can be similar or different represents hydrogen, halogen atom, cyano-group, (C1-C6)-alkyl, (C2-C8)-alkenyl, (C2-C8)-alkynyl and (C1-C6)-alkoxy-group, or G1 and G2 form in common group of formulae -CH=CH-CH=CH-, -CH=CH-O- or -O-CH=CH- being each group carries optionally halogen atom as a substitute, or G1 and G2 form in common group of formulae -O-CH2-O- or -O-CH2-CH2-O-, or -O-CH2-CH2-O-, and each among G3 and G4 represents hydrogen atom, and G5 is chosen from hydrogen and halogen atom. Proposed compounds possess anti-tumor activity and designated for preparing a medicine preparation for its using as an anti-tumor agent for suppression and/or treatment of solid tumors. Also, invention relates to a pharmaceutical composition based on abovementioned compounds.

EFFECT: valuable medicinal properties of compounds.

20 cl, 7 tbl, 57 ex

FIELD: organic chemistry, medicine, oncology, pharmacy.

SUBSTANCE: invention relates to new sulfonamide derivatives possessing anti-tumor activity, namely to compounds of the formula (I): wherein R6 means hydroxyl; R7 means methyl, isopropyl, isobutyl, benzyl or indole-3-ylmethyl; R8 means hydrogen atom; R9 means phenylene; R10 means thienyl, furyl or pyridyl optionally substituted with lower alkyl or halogen atom. Also, invention relates to their derivatives or pharmaceutically acceptable salts or solvates. Invention describes medicinal agents used in treatment or prophylaxis of cancer and for prophylaxis of metastasis. Also, invention describes a case for treatment of cancer in mammal.

EFFECT: improved treatment method, valuable medicinal properties of agent.

5 cl, 17 tbl, 112 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new biologically active ortho-substituted nitrogen-containing bis-aryl compounds. Invention describes compounds of the formula (I): wherein A1, A2, A3, A4, A5, A6, A7 and A8 mean independently of one another nitrogen atom or -CH and wherein at least one or two (not above) these groups mean nitrogen atom; R(1) means -C(O)OR(9) or -COR(11) wherein R(9) and R(11) mean independently of one another CxH2x-R(14) wherein x has a value 0, 1, 2, 3 or 4 and R(14) means alkyl c 1, 3, 4, 5 or 6 carbon atoms, phenyl or isoxazolyl wherein phenyl and isoxazolyl are not substituted or substituted with 1, 2 or 3 substitutes chosen from the group consisting of F, Cl, Br, J, CF3, OCF3, alkyl with 1, 2, 3 or 4 carbon atoms and alkoxy-group with 1, 2, 3 or 4 carbon atoms; R(2) means hydrogen atom; R(3) means CyH2y-R(16) wherein y has a value 0, 1, 2, 3 or 4but y can't mean 0 if R(16) means -OR(17), and R(16) means alkyl with 1, 2, 3, 4, 5 or 6 carbon atoms, cycloalkyl with 3 carbon atoms, -OR(17), phenyl or pyridyl wherein phenyl and pyridyl are not substituted or substituted with 1, 2 or 3 substitutes chosen from the group consisting of F, Cl, Br, J and alkoxy-group with 1, 2, 3 or 4 carbon atoms; R(17) means hydrogen atom; or R(3) means -CHR(18)R(19) wherein R(18) means alkyl with 1, 2, 3, 4, 5 or 6 carbon atoms and R(19) means -CONH2; R(4) means hydrogen atom; R(30) and R(31) mean hydrogen atom, and their pharmaceutically acceptable salts also. Also, invention describes a pharmaceutical composition showing effect that inhibits K+-channel and comprising the effective amount of at least compound of the formula (I) and using compounds of the formula (I). Invention provides preparing new compounds possessing useful biological properties.

EFFECT: valuable medicinal properties of compounds and composition.

10 cl, 8 tbl, 35 ex

FIELD: organic chemistry, biochemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new derivatives of 3-aminomethylquinolone-2 of the general formula (1)

(2)

or (3) wherein R1 means hydrogen atom (H) or Alk; R2 is taken among Alk; -OAlk, -SCH3, -Hal, -CF3, 3,4-OCH2CH2O-, 3,4-OCH2O-, 4-OCF3, 2-Ph, -OPh, -NHCOR, 2-OCH3, 5-Ph, 4-Obzk, 3-NO2, 2-CH3, 5-iPr, di-OAlk, di-Hal; or R2 represents halogen atom and alkyl group, or halogen atom and alkoxy-group taken simultaneously and independently of one another; or R2 represents the group -CONR4R5 wherein each R4 and R5 means independently of one another the group Alk, or they form the group -(CH2)n- wherein n = 2-6. R means -CH3; R3 means hydrogen atom (H); X is taken among hydrogen atom (H), 6-(C1-C3)-Alk, 6-iPr, 6-iBu; 7-(C1-C2)-Alk, 8-(C1-C2)-Alk, 6-(C1-C2)-OAlk, 6-OCF3, 7-(C1-C2)-Alk, 7-SCH3, 6,7-OCH2O-, 6,7-OCH2CH2O-, 5,6,7-OCH3, 6-F; X and Y are similar or different and taken among 7,8-CH3, 6,8-CH3, 5,8-CH3, 5,7-CH3, 6,7-CH3, 6,7-OCH3, 6-CH3, 7-Cl. Also, invention relates to a method for preparing indicated compounds and to pharmaceutical composition inhibiting activity of NO-synthetase based on these compounds. Invention provides preparing new compounds and pharmaceutical composition based on thereof for aims preparing medicinal agents for treatment diseases associated with hyperactivity of phagocytizing cells, for example, rheumatic arthritis, asthma and others.

EFFECT: improved preparing method, valuable medicinal and biochemical properties of compounds and pharmaceutical composition.

19 cl, 1 tbl, 95 ex

FIELD: organic chemistry, pharmacy.

SUBSTANCE: invention relates to compounds of the general formula (I) and pharmaceutical composition based on thereof possessing properties of ligand binding with adenosine receptors selectively. Invention provides preparing new compounds possessing useful biological properties.

EFFECT: valuable properties of compounds.

6 cl, 375 ex

FIELD: organic chemistry, biochemistry.

SUBSTANCE: invention relates to substituted 3-phenyl-5-alkoxy-1,3,4-oxadiazol-2-ones of the formula (1):

wherein R1 means (C1-C6)-alkyl that can be substituted once or multiply with phenyl; R2 and R3 means independently of one another hydrogen atom, (C6-C10)-aryl, (C3-C8)-cycloalkyl, (C6-C10)-aryloxymethyl, O-benzyl can be substituted once or multiply with halogen atom, -CF3,, O-(C6-C10)-aryl or O-(C3-C8)-cycloalkyl, O-(C1-C6)-alkyl, that can be substituted once or multiply with fluorine atom or amino-group wherein amino-group, in turn, can be substituted once or multiply with (C1-C4)-alkyl; SO2-NH-(C1-C6)-alkyl substituted possibly with group N-[(C1-C6)-alkyl]2; SO2-NH-(2,2,6,6-tetramethylpiperidin-4-yl); SO2-NH-(C3-C8)-cycloalkyl substituted possible once or multiply with (C1-C4)-alkyl; SO2-N-[(C1-C6)-alkyl]2 or COX wherein X means N-[(C1-C6)-alkyl]2; and N-[(C1-C6)-alkyl-alkyl]2 can mean also pyrrolidine, piperidine, morpholine or piperizine group that if necessary can be substituted with (C1-C4)-alkyl; under condition that R2 and R3 don't mean hydrogen atom simultaneously, and to their physiologically acceptable salts and optical isomers. Compounds show inhibitory effect on activity of hormone-sensitivity lipase (HSL). Also, invention describes a method for preparing these compounds.

EFFECT: valuable medicinal and biochemical properties of compounds.

9 cl, 43 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new derivatives of isoquinoline carboxamide of the formula (I):

and to their pharmaceutically acceptable salts wherein R1 means hydrogen atom, hydroxy-group or -NHR2 wherein R2 means alkyl, arylalkyl, heterocyclylalkyl that comprises one or some heteroatoms taken among nitrogen, oxygen and sulfur atoms, cycloalkyl, alkylcarbonyl, cycloalkylcarbonyl, arylcarbonyl, heterocyclylcarbonyl that comprises one or some heteroatoms taken among nitrogen, oxygen and sulfur atoms, arylalkylcarbonyl, heterocyclylalkylcarbonyl that comprises one or some heteroatoms taken among nitrogen and oxygen atoms, alkyloxycarbonyl, arylalkyloxycarbonyl, heterocyclylalkyloxycarbonyl that comprises one or some heteroatoms taken among nitrogen atom, heterocyclyl that comprises one or some heteroatoms taken among nitrogen and sulfur atoms, alkylsulfonyl, arylsulfonyl or the group of the formula:

R3 and R4 mean alkyl independently of one another; R5 means alkyl; or R4 and R5 in common with carbon and sulfur atoms to which they are bound form a heterocycle; R6 means alkyl; R13 means hydrogen atom or the group of the formula:

R15 means aryl under condition that if R3, R4 and R5 form methyl, R6 forms tert.-butyl then R13 means hydrogen atom, and if R15 means phenyl then R2 doesn't mean benzyloxycarbonyl and 2-quinoline carbonyl (other values of radicals are given in cl. 1 of the invention claim). Also, invention relates to a medicinal agent based on these compounds used in treatment of HIV-mediated diseases. Invention provides preparing new compounds and a medicinal agent based on thereof in aims for treatment of HIV-mediated diseases.

EFFECT: valuable medicinal properties of compounds and medicinal agent.

14 cl, 11 tbl, 173 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new nitrogen-containing aromatic derivatives of the general formula:

wherein Ag represents (1) group of the formula:

; (2) group represented by the formula:

or ; (3) group represented by the formula:

; Xg represents -O-, -S-, C1-6-alkylene group or -N(Rg3)- (wherein Rg3 represents hydrogen atom); Yg represents optionally substituted C6-14-aryl group, optionally substituted 5-14-membered heterocyclic group including at least one heteroatom, such as nitrogen atom or sulfur atom, optionally substituted C1-8-alkyl group; Tg1 means (1) group represented by the following general formula:

; (2) group represented by the following general formula: . Other radical values are given in cl. 1 of the invention claim. Also, invention relates to a medicinal agent, pharmaceutical composition, angiogenesis inhibitor, method for treatment based on these compounds and to using these compounds. Invention provides preparing new compounds and medicinal agents based on thereof in aims for prophylaxis or treatment of diseases wherein inhibition of angiogenesis is effective.

EFFECT: improved treatment method, valuable medicinal properties of compounds and agents.

40 cl, 51 tbl, 741 ex

FIELD: pharmaceutical chemistry, medicine.

SUBSTANCE: present invention relates to new heterocyclic derivatives having calpain inhibition activity or oxygen reactive form recovering entrapping activity of formula I

1, wherein Het represent monocyclic 5-6-membered hetericyclic radical containing 1-2 heteroatoms selected from O or N; A represents A1

2, A'1 3, A2 4, A3 5 and A4 6; X represent -(CH2)n-, -(CH2)n-CO-, -N(R45)-CO-(CH2)n-CO, -CO-N(R45)-D-CO-, -N(R45)-(CH2)n-CO-, -N(R45)-CO-C(R46R47)-CO-, -O-(CH2)n-CO-, -N(R45)-CO-NH-C(R46R47)-CO-, -CO-N(R45)-C(R46R47)-CO- or -Z-CO Y represents -(CH2)p-, C(R53R54)-(CH2)p-, C(R53R54)-CO-; R1 represents hydrogen, group CR3 or oxo; R3 represents hydrogen, monocyclic saturated 6-membered heterocycloalkylcarbonyl, wherein heterocycle contains two heteroatoms selected from nitrogen or oxygen, C1-C6-alkylcarbonyl, phenylcarbonyl or phenyl(C1-C6)-alkylcarbonyl optionally substituted with NR4R5, or R4 and R5 independently represent C1-C6-alkyl; R2 represents hydrogen, and pharmaceutical compositions containing the same.

EFFECT: new heterocyclic drugs.

18 cl, 37 ex

FIELD: pharmaceutical chemistry.

SUBSTANCE: invention relates to new amide derivatives of general formula I

1, as well as to pharmaceutical acceptable salts or cleaving in vivo esters thereof. Claimed compounds are capable to inhibit cytokine production due to inhibition of p38 kinase action and are useful in treatment of various diseases such as inflammation or allergic disorders. Also are disclosed methods for production the same, pharmaceutical composition and method for inhibition of TNFα cytokine production. In formula I X is -NHCO- or -CONH-; m = 0-3; R1 is halogen, C1-C6-alkoxy, N-(C1-C6)-alkyl-di{(C1-C6)-alkyl]-amino-(C2-C6)-alkylamino, or heterocyclyl, heterocyclyl-(C1-C6)-alkyl, heterocyclyloxy, heterocyclyl-(C1-C6)-alkoxy, heterocyclylamino, N-(C1-C6)-alkylheterocyclylamino, heterocyclyl-(C1-C6)-alkylamino, N-(C1-C6)-alkylheterocyclyl-(C1-C6)-alkylamino, heterocyclylcarbonylamino, heterocyclylsulfonylamino, N-heterocyclylsulfamoyl, heterocyclyl-(C2-C6)-alkanoylamino, heterocyclyl-(C1-C6)-alkoxy-(C1-C6)-alkyl, heterocyclyl-(C1-C6)-alkylamino-(C1-C6)-alkyl, or N-(C1-C6)-alkylheterocyclyl-(C1-C6)-alkylamino-(C1-C6)-alkyl, wherein any of heterocylyl in R1 optionally may contain 1 or 2 substituents selected from oxo- or thioxogroup; n = 0-2; R2 is hydrogen or C1-C6-alkyl; R2 is hydrogen, C1-C6-alkyl or C1-C6-alkoxy; q = 0-4; Q is aryl, aryloxy, etc.

EFFECT: new inhibitors of cytokine production.

13 cl, 8 tbl, 20 ex

FIELD: organic chemistry, technology of organic compounds.

SUBSTANCE: invention relates to heterocyclic o-dicarbonitriles. Invention describes heterocyclic o-dicarbonitriles of the general formula: wherein R means the following compounds: . Heterocyclic o-dicarbonitriles can be used for preparing hexazocyclanes-fluorophores as a donor-fragment used for preparing hexazocyclanes-bifluorophores and hexazocyclanes-trifluorophores. Invention provides preparing new compounds possessing valuable properties.

EFFECT: valuable properties of compounds.

2 tbl, 10 ex

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