Heterocyclic compounds used in treatment of age and diabetic vascular complication

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to a novel class of 5-membered heterocyclic compounds of the general formula (I): or cosmetically acceptable salts. Invention describes a compound represented by the formula (I) and its pharmaceutically or cosmetically acceptable salt wherein R1 is chosen from linear or branched (C1-C12)-alkyl, (C3-C7)-cycloalkyl, phenyl, naphthyl, C3-, C4-, C5- or C8-heteroaryl wherein one or some heteroatoms when they present are chosen independently from oxygen (O), nitrogen (N) or sulfur (S) atom and substituted optionally wherein substitutes are chosen from the first group comprising halogen atom, hydroxy0, nitro-, cyano-, amino- oxo-group and oxime, or from the second group comprising linear or branched (C1-C8)-alkyl wherein a substitute from indicated second group is optionally substituted with R10, or wherein heteroaryl is substituted with -CH2-C(O)-2-thienyl; Y is absent or chosen from the group consisting of (C1-C12)-alkyl-Z or (C2-C8)-alkyl wherein Z is chosen from sulfur, oxygen or nitrogen atom; A and B are chosen independently from nitrogen atom (N), -NH, -NR6, sulfur, oxygen atom to form heteroaromatic ring system; R2, R3 and R4 are chosen independently from the first group comprising hydrogen, halogen atom, or R3 and R4 form phenyl ring in adjacent positions; R5 is absent or chosen from the group comprising -CH2-phenyl, -CH2(CO)R7, -CH2(CO)NHR8 and -CH2(CO)NR8R9 that are substituted optionally with R10; R6, R7, R8 and R are chosen independently from the group comprising linear or branched (C1-C8)-alkyl, (C3-C7)-cycloalkyl, C5-heterocycloalkyl, benzylpiperidinyl, phenyl, naphthyl, heteroaryl, alkylheteroaryl, adamantyl, or R8 and R9 form piperidine ring, and R means 3,4-ethylenedioxyphenyl wherein substitutes in indicated group are substituted optionally with R10, and heteroaryl means C3-, C4-, C5- or C8-heteroaryl wherein one or some heteroatom when they present are chosen independently from O, N or S; R10 is chosen from halogen atom, hydroxy-, nitro-, cyano-, amino-, oxo-group, perhalogenalkyl-(C1-C6) or oxime; X means halide ion under condition that when groups/substitutes present at the same or at adjacent carbon or nitrogen atoms then can form optionally 5-, 6- or 7-membered ring optionally containing one o some double bonds and containing optionally one or some heteroatoms chosen from O, N or S. Also, invention describes a method for synthesis of these compounds, their therapeutic and cosmetic using, in particular, in regulation of age and diabetic vascular complications. Proposed compounds show effect based on the triple effect as agent destroying AGE (terminal products of enhanced glycosylation), inhibitors of AGE and scavengers of free radicals that do their suitable in different therapeutic and cosmetic using. Also, invention relates to pharmaceutical and cosmetic compositions comprising these compounds and to methods for treatment of diseases caused by accumulation of AGE and/or free radicals in body cells. Invention provides synthesis of novel compounds possessing useful biological properties.

EFFECT: valuable medicinal properties of compounds.

73 cl, 4 tbl, 63 ex

 

The scope of the invention

The present invention relates to a new class of five-membered heterocyclic compounds and to their use for the treatment of diabetes and related diseases. More specifically, the invention relates to compounds of this series, to methods for their preparation, pharmaceutical compositions containing these compounds, and their use for the treatment of diabetes. The compounds of this series have destructive and inhibiting AGE (end products increased glycosylation) activity, which is essential for the treatment of diabetic and age-related vascular and neurovascular complications, including kidney disease, nerve disease, atherosclerosis, retinopathy, inflammatory diseases, immunological disorders, oxidative stress, and dermatological and cosmetic indications.

The invention also relates to a method for restoring color change of teeth resulting from nonenzymatic Browning in the oral cavity, through the introduction of an effective amount of these compounds for the destruction of previously formed structure as a result of increased glycosylation.

These compounds also have activity removal of free radicals and, therefore, in addition to their cosmetic applications, can be used in the treatment of diseases caused by free radicals.

The triple function of these compounds as scavengers of free radicals that AGE the damaging agent and AGE inhibitor can be effectively used in cosmetic compositions, which can be stopped and turned back the aging process of the skin resulting in the accumulation of end products increased glycosylation (AGE) proteins of the skin and light damage due to free radicals. The invention additionally relates to a composition and method of removing free radicals from the cells of the body.

Background of invention

In 1912 Maillard found that recovering sugars such as glucose and ribose, react with proteins with the formation of brown pigments. Additional studies have shown that this is an irreversible non-enzymatic interaction, which occurs in some natural systems, including food products during storage. There are two phase reaction of Maillard (Maillard), early and developed. Originally proteins react with glucose with the formation of stable products Amadori (Amadori), which are then cross-stitched with the formation of the final products increased glycosylation (AGE). In most cases, education, AGE is also accompanied by darkening of proteins and increased fluorescence.

In diabetes, when the level of glucose in the blood su is the natural enemy above normal, the reaction of glucose with several proteins, such as hemoglobin, kristallin eye lens and collagen, causes the formation of AGE, which, in turn, are responsible for complications associated with diabetes, such as nephropathy, microangiopathy, endothelial dysfunction and dysfunction of other organs. In addition, the activity of several growth factors such as basic fibroblast growth factor, also deteriorates. Products AGE, in contrast to normal tissue proteins, have a lower rate of turnover and replenishment. It was reported that the products AGE can really cause a complex immunological response, including RAGE receptors (receptor for final products increased glycosylation) and activation of several not fully certain of immunological processes. Documented that diabetes signs of microangiopathy and macroangiopathies also manifest symptoms of oxidative stress, the mechanism of which is not clear.

In vitro formation of AGE can be studied in a laboratory incubation of reducing sugars, such as ribose and glucose, with bovine serum albumin. Education AGE may be detected by the increase in fluorescence or increase the reactivity of the crosslinking with anti-AGE antibodies. It turns out that the increase in fluorescence of p is exectued education AGE-specific antigenic epitopes. This increase in fluorescence is used to monitor higher education AGE in vitro (Brownlee, M. et al, Science 1986; 232: 1629-1632). In addition to an increase in fluorescence, one of the most distinctive characteristics AGE education in vitro, is the formation of antigenic epitopes that are specific to AGE and are not specific to natural proteins. Consequently, it is possible to generate antibodies against the final products increased glycosylation and use them for the detection of education AGE in other proteins. This was an important analytical tool in the study of AGE.

Due to the clinical importance of education AGE was used many approaches to diagnosis, prevention, or return to the previous state education AGE in the body. Education AGE could inhibit due to the interaction with a product of the early glycosylation, which occurs when the initial reaction of the target protein and glucose. It is assumed that the inhibition occurs as the interaction between the inhibitor and the product of the early glycosylation that, apparently, interrupts subsequent reaction glycosylated protein with additional protein, resulting crosslinked product of the last stage. Compounds such as aminoguanidine, inhibit the formation of AGE, dei is twua by this mechanism.

Education AGE on long-lived proteins is also associated with structuring (cross-linking) of these proteins. It was shown that obtained from AGE-structured proteins are destroyed by such compounds as bromide N-phenylthiazole (PTB), which interacts with them and cleaves the covalent obtained from AGE-structured proteins (Vasan et al. Nature 1996; 382: 275-278; US 5853703, issue date of patent: Dec. 29,1998). It is assumed that the mechanism of reducing the content of AGE in tissues is relatively fast, as opposed to aminoguanidine, which acts slowly because of the very nature of the mechanism of its action.

The greatest importance in therapeutic applications have connections that are AGE-destroying agents or AGE inhibitors, as noted below:

Agents that Deplete AGE:

Compounds that can break down accumulated AGE, can be used as a drug in the treatment of diabetic complications and age-related diseases caused by the accumulation of AGE.

Compounds that can inhibit the accumulation by AGE of destruction AGE, can be used as a drug to stop the worsening of diseases such as diabetes and age-related complications caused by the accumulation of AGE.

Inhibitors AGE:

Compounds that can inhibit NAC is the arrival AGE by inhibiting the formation of AGE, can be used as a medicine for diseases such as diabetes and age-related complications caused by the accumulation of AGE.

Uncontrolled education AGE in vivo, such as in diabetes-related diseases, can lead to serious physiological deterioration. For example, in diabetic neuropathy and retinopathy damaged the functional integrity of the barrier wall of the capillary and the inner blood retinal barrier, respectively, as evidenced by abnormal adherence of the endothelium to the basal membrane. This defect is a direct result of cross-linkage of structural proteins by glycosylation. The etiology of diabetic neurovascular diseases and immunological disorders is the formation of AGE. Currently, it is assumed that the inhibition of AGE formation or destruction of existing AGE will be advantageous for many diseases, including nephropathy, neuropathy, atherosclerosis and dermatological diseases.

Studies have demonstrated the positive effect of agents that destroy AGE, for example, when studying the cardiovascular complications associated with age, disease state, which is increased in experimental diabetic conditions (Wolffenbuttel et al., 1998).

In another pharmacological approach on the I control AGE levels in tissues, especially in those tissues in which AGE has already accumulated to a level that is responsible for subclinical or clinical pathology, has been successful introduction of an agent that destroys or disrupts AGE. In U.S. patent 5656261 and 5853703 described agents and methods that destroy (or break down, or destroy) education AGE in vitro and in vivo.

Also achieved several successful therapeutic approaches based on blocking the accumulation of AGE in vivo. One approach, illustrated in U.S. patent 4758583 relates to inhibiting the formation of AGE from its predecessors by introducing such agents as aminoguanidine and related compounds.

As shown in the above-quoted references, compounds that inhibit the formation of AGE or destroy AGE, it is logical correlate with the treatment of AGE-related diseases such as diabetic nephropathy, neuropathy, retinopathy, and atherosclerosis, dermatological diseases, the nonenzymatic Browning in the oral cavity, endothelial dysfunction or dysfunction of other organs and growth impairment.

In various literary sources, discussed below, has also been described correlation between early AGE and various diseases.

The correlation between the formation of the final products increased glycosylation (AGE) and nephropathy well supported by ascoltami research publications. Beisswenger (1995) showed that the concentration of AGE in people with diabetes correlates with early manifestations of renal diseases. Makita et al. (1991) showed that the increase of the content of AGE of peptides occurs in parallel with the severity of renal dysfunction. The links above clearly show that AGE is the principal cause of diabetic nephropathy. Yamauchi (1997) showed that prevent the formation of AGE with aminoguanidine inhibits the development of diabetic nephropathy. It is also shown that the introduction of aminoguanidine improves the thickening of the basal membrane of the glomeruli from diabetic rats (Ellis, 1991). It is also shown that aminoguanidine attenuates the increase in albuminuria in experimental diabetic rats (Soulis-Liparota, 1991).

It also shows that AGE induces the expression of endothelial growth factor in mallery the retinal cells (Hirata, 1997, Murata, 1997) and, therefore, can promote intraocular neovascularization (formation of new blood vessels) in diabetic retinopathy. In a rat model it was shown that treatment with aminoguanidine delays the development of diabetic retinopathy (Hammes, 1991, Hammes, 1994, Roufail, 1998).

Also shown that treatment with aminoguanidine improves the speed of nerve conduction in diabetic rats (Kihara, 1991, Miyauchi, 1996 and Yagihashi, 1992).

Bucala (1996) conducted an intensive overview of the different and the perspective of the development of atherosclerosis and installed, the accumulation of AGE initiates a series of cellular events such as cell oxidative stress, expression of adhesion molecules, endothelial transmigrate monocytes and so on, and such events can lead to atherosclerosis. Go directly (1990) demonstrated that (i) in vitro and in vivo-formed AGE proteins are hemotoxicity for monocytes in human blood, (ii) subendothelial AGE can induce the migration of monocytic through intact endothelium, and (iii) the interaction of monocyte with AGE-containing matrix leads to the induction of platelet-derived growth factor.

Thus, we can conclude that AGE when interacting with endothelial cells via receptor RAGE activates nuclear factor Kappa B and induces various genes expressing adhesion molecules. The interaction of AGE-endothelium also increase oxidative stress, initiate the migration of monocytes, inhibit endothelial nitric oxide and stimulate angiogenesis. All these conditions lead to such conditions as atherosclerosis.

Other dysfunction-dependent lowering of the load AGE in tissues include hypertension, restenosis, abnormal obstacle tissue in peritoneal dialysis, erectile dysfunction and Alzheimer's disease. Similarly, on the one hand, nonenzymatic binding of structured proteins, such as collagen, leads to p is increased stiffness of arteries and reduces compliance and distensibility of the arteries. Indeed, it was shown that treatment with ALT-711-an agent that destroys AGE, eliminates induced diabetes stiffness of the arteries and improves arterial compliance (Wolffenbutel, 1998). Aronson et al. (1996) published a review on the role of AGE in the promotion of the increase in the number of inflammatory cells and proliferation of smooth muscle and suggested that this is likely the main cause of restenosis, abnormal obstacles tissue in peritoneal dialysis in diabetic patients.

Seftel (1997) showed a significant increase in pentosidine in the tissue of penis in patients with diabetes compared with patients not suffering from diabetes. He discusses the mechanism of AGE-mediated erectile dysfunction by increased regulation stimulated nitric oxide and reduced regulation of endothelial nitric oxide in the tissue of the penis.

Vitek et al. (1994) reported that beta-amyloid peptides (βAP) slow grouped under normal physiological conditions, whereas AGE modified (βAP) shows a much more rapid aggregation. The number of platelets is increased by the degeneration of neurons, and in Alzheimer's disease quenched knowledge. Aggregated, but not Monomeric βAP are actively neurotoxic. Therefore, interference in the process by which education AGE at elicium aggregation β AP, or inhibition of AGE formation, or therapy with the destruction of AGE provides a new therapeutic opportunities to reduce the pathophysiological changes associated with Alzheimer's disease.

Therefore, AGE inhibitors/destructive agents would be favorable to reduce aggregation (βAP), providing prevention/treatment of Alzheimer's disease.

Li et al. (1996) confirmed the internal relationship between the two key manifestations of physiological aging on rat models of cardiovascular and renal fading, and suggested that the directly age-related biochemical processes, ending in an increased glycosylation contribute to progressive tissue damage and failure of organs. In their study, it was found that aminoguanidine (an inhibitor of AGE) largely prevents tissue damage as a result of inhibition of AGE formation. It was found that the lower load AGE in tissues of rats as a result of introduction aminoguanidine saves more satisfactory overall level of cardiovascular and renal function, which is confirmed by a more healthy overall look of old rats exposed to treatment aminoguanidine, compared with non-treated rats from matched on age and weight of the control group. Consequently the nutrient, inhibitors of AGE could find a use for the prevention of age-related diseases.

The reaction nonenzymatic Browning (brown color), which occurs in the oral cavity leads to teeth discoloration. It was reported that agents against plaque formation, such as chlorhexidine, accelerate the reaction of nonenzymatic Browning and subsequent staining of teeth (Nordbo, J. Dent. Res., 58, p. 1429 (1979)). Nordbo suggested that chlorhexidine causes staining of teeth in two ways: first, by increasing the formation of plaque, which contains more amino groups, and, secondly, due to the catalysis reaction of Maillard, leading to colored products.

The ability of inhibitors of nonenzymatic reactions darkening to prevent the color change of the protein on the surface, such that occurs on the tooth surface, has been demonstrated in vitro experiments in U.S. patent 5137916 and 5272176.

It was stated that compounds that have the ability to inhibit or eliminate AGE, can be used for the inhibition or elimination of teeth discoloration as a result of nonenzymatic Browning in the oral cavity (U.S. Patent 5272176; U.S. Patent 5853703).

All these facts point to a common underlying mechanism for pathophysiological conditions associated with diabetes, and that it represents the image is of the final products increased glycosylation. As the total AGE of the fabric load increases, the severity of the pathological symptoms also increases. On the other hand, if the number of AGE is controlled with such compounds as aminoguanidine, disease progression is also slowing. In the present invention are described inhibition of the final products increased glycosylation. Renal disease is a leading cause of death and the source of trouble in diabetes. Chronic dialysis and kidney transplantation are absolutely normal for patients with renal insufficiency as a result of diabetes. Peritoneal dialysis (PD) works on the same principles as hemodialysis, but the blood is cleaned when it is inside the body, and not by machine. The main difference in the medications for peritoneal dialysis compared with hemodialysis is the number of higher concentrations of glucose, used as an osmotic agent (1,5, 2,5 or of 4.25 g/DL). High formation of glucose in humans is associated with progressive formation of the final products increased glycosylation (AGE), which damage the functions of the authority. AGE contributes to the development of abnormal fibrous tissue and reduces the ability of the peritoneum to filter fluid, leading to the insolvency of PD treatments.

Compounds that can modify the contents of AGE in the tissue, could be used to prevent this process and other medical complications that arise because of the formation of AGE. The use of an agent that destroys AGE, or inhibitor in the fluid for dialysis could inhibit the formation of abnormal fibrous tissue and ease, thus, the dialysis procedure. Accordingly, the compounds of the invention can be used to obtain fluid for dialysis peritoneal dialysis (PD) patients diabetics.

It is expected that reducing the burden of AGE in the tissue will eliminate data morbid state, taking into consideration that prevent the accumulation of a critical mass could prevent painful conditions. Data morbid condition are listed below:

1) vascular and neurovascular complications

2) renal disease,

3) neurological disease,

4) atherosclerosis

5) disease of the retina

6) dermatological disease,

7) the nonenzymatic Browning in the oral cavity,

8) endothelial dysfunction or dysfunction of other organ

9) growth impairment,

10) inflammatory disease

11) immunological violation

12) oxidative stress,

13) the age and diabetic complications,

14) Alzheimer's disease,

15) restenosis, abnormal barrier fabric when Periton the flax dialysis,

16) abnormal permeability of the tissue in peritoneal dialysis, and

17) erectile dysfunction.

The compounds exhibiting destructive AGE/inhibitory activity, can also be used for cosmetic purposes.

Health, elasticity and youthfulness of the skin depend, among other things, on some of the key classes of biological molecules. The key molecules of the skin are collagen and elastin. Collagen is a protein that forms the structural grid, which carries the other structures of the skin. He gives skin its strength and durability. Like any other protein, collagen is composed of amino acids. However, he was unusually rich in several specific amino acids: Proline, hydroxiproline, lysine and glycine. Elastin is also a protein that is more flexible than collagen, and helps to maintain the firmness and elasticity of the skin. It contains two specific amino acids: desmosine and isodesmosine. When both elastin and collagen are insufficient and damaged, the skin loses its shape after stretching or bending, leading to wrinkles and slight sagging that occurs during the aging process.

Most modern theories of aging focused around the idea that age-related damage in the first place is due to structural and functional modificat the th cell components. Currently popular hypotheses are theories of aging as free radical, glycosylation or theory of Mallard. The first hypothesis assumes that the age effects are due to the reactions of free radicals, which damage the components of cells. The term "free radical" refers to an unstable molecule that has an unpaired or odd electron in the outer orbit, which in a special way interacts with other molecules, causing damage to fats, protein and DNA. The last hypothesis suggests that the primary cause of aging is cellular damage resulting from modification of macromolecules caused by nonenzymatic glycosylation and reactions of Mallard with the formation of the final products increased glycosylation (AGE). Nonenzymatic glycosylamine is a chemical attach sugars to protein, which ultimately causes the crosslinking of proteins, which is irreversible. Although these hypotheses were formulated independently, this suggests that free radicals, glikozilirovanie and reactions of Maillard may actually be a partially influencing each other the elements of a single, more complex biochemical pathway, and that age-related deterioration is going on is it the amount of damage induced by all three hypothetical ways and through their interaction.

Leather, highly differentiated and complex organ, are particularly susceptible to damage by free radicals under the action of ultraviolet radiation, leading to increased accumulation of AGE on the skin, as well as to increased production of singlet oxygen and peroxy radicals that damage important molecules in the skin such as collagen and elastin. In such situations, antioxidant conditions for the removal of free radicals could, of course, to enable the skin to maintain its normal elasticity and integrity against damage.

Thus, the present invention relates to the cosmetic use of an active molecule capable of destroying AGE cross-linkage and antioxidant create the environment in tissues with AGE destructive and quenching free radicals action, as a consequence, significantly slowing down the signs of aging.

The skin is the largest organ of the body, accounting for about 15% of body weight. In terms of the chemical composition of the skin is about 70% water, 25% protein and 2% fat. The remainder includes traces of minerals, nucleic acids, glucosaminoglycans, proteoglycans and numerous other chemical compounds.

The skin consists of 3 main layers: the of epidermis, the dermis and subcutaneous tissue. The epidermis is the first barrier between us and the outside world. This layer consists of cells 3 types: keratinocytes, melanocytes and cells of Langhans. The dermis is the middle layer of the skin, the most thick layer of skin, and includes a tight-fitting durable network of collagen (type-I and III and elastin fibers, which are critical proteins in the skin. The dermis consists of fibroblasts, capillaries, lymph glands, sebaceous glands and hair follicles. Subcutaneous tissue is the inner layer of the skin, including many adipocytes and acts as a shock absorber and a heat-insulating material that protects the underlying tissue from cold and mechanical injury.

Aging is a biological phenomenon that manifests itself in wrinkles and sagging skin. As a person ages the skin cells divide more slowly and the inner skin, or the dermis, begins to thin. Fat cells below the dermis, begins to atrophy, and the underlying network of elastin and collagen fibers, which provides support for the surface layer is lost and rasparivaetsya. The skin loses its elasticity; when pressed, it no longer springs back to its original position, but instead sags and forms deep the e wrinkles. The skin's ability to retain moisture decreases; the sweat glands and eurosclerosis gland atrophy, depriving the skin of its protective emulsions water - fat. As a result, the skin becomes dry and layered. In addition, the skin's ability to regenerate declines with age, so wounds heal more slowly. The line about eyebrows (between the eyebrows) and crow's feet (lines that radiate out from the corners of the eyes) begin to develop through constant small muscle contractions. Normal facial expression also forms a characteristic line, and the force of gravity exacerbates the situation, contributing to the formation of the second chin and his age. Because the skin is the most visible organ during aging, there is an increased interest in physiology and remove wrinkles, elastosis and senile xerosis. Skin aging is a complex phenomenon, determined by factors in genetically defined intrinsic aging and external factors of aging (Boni R, Burg g: Schweiz Med Wochenschr (2000) Sept 9; 130 (36): 1272-8).

Mainly, there are two biologically independent of the aging process, which occur simultaneously and are responsible for the major changes appear on the skin with the passage of time.

1. External aging or photoaging/external factors and

2. Inherent in the nature of aging or vnutrennyaya/internal factors.

External aging or photoaging, which occurs when the skin is subjected to the action of factors such as ultraviolet radiation, chemical pollution, allergens, mechanical damage, etc. primarily external aging caused by ultraviolet radiation from the sun.

Internal aging effects on the skin, causing a slow irreversible degeneration of tissue. Factors that cause internal aging is genetic, neural (stress), the immune, the result of hormonal disorders and others. Intrinsic aging can be observed over the entire surface of the body, including the skin protected from the sun's ultraviolet rays. The phenomenon of glycosylation, as discussed above, plays a significant role in the internal aging. Proteins of the dermis, elastin and collagen, interact with sugars in the body, especially with glucose, resulting in the linking of collagen fibers and the synthesis of free radicals. It modifies the structure of the skin, causing it to lose its elasticity and it becomes more rigid. Thus, the most noticeable changes in the skin occur due to a combination of internal and external aging.

Mainly two factors - the free radicals AGE and education are significant accelerators formation of wrinkles on the skin. Theory of Maillard article is rhenium skin refers to 1912, when Millard found that reducing sugars such as glucose and ribose, interact with proteins with the formation of brown pigments. The reaction of Maillard is a series of complex interactions that cause cross-linking of protein by the interaction of reducing sugars with amino groups of proteins with the formation of stable products Amadori (Amadori), which are then stitched together with the formation of the final products increased glycosylation (AGE). Another property that has a crucial biological importance is the observation that the products Amadori continue to sew and to cure even in the absence of free glucose. Cross-linking of protein is important because it is responsible for the formation of deep wrinkles of the dermis. Education AGE stapling is also a natural part of aging, and all processes, in which the aging of the protein, causing serious damage. During the process of aging revitalizing sugar chemically attached to the supporting skin proteins like elastin and collagen, making out gradually become hard and slowing their update. Such non-specific and non-enzymatic joining of sugar to collagen and elastin leads to the formation of AGE who continue to sew and to polymerization on the same in the absence of free glucose. The study of the role of AGE in aging collagen using a scanning force microscope revealed that in the presence of elevated concentrations of AGE there are significant structural changes in the collagen fibrils old rats (Odetti p, Aragno I., et al. Gerontology (1998); 44 (4); 187-91). As a result of this aging process, the collagen loses its elasticity and the skin develop wrinkles.

Covalent binding of glucose with the amino group of the protein is too low for it to be responsible for the structural changes observed in the collagen. Oxygen radicals formed during the oxidation of glucose, and the oxidation of glycated protein can be directly involved in the formation of AGE and crosslinking of collagen. In vitro studies have demonstrated that the presence of oxygen is necessary for increased glycosylation and cross-linking collagen. It was confirmed that the anti-oxidative conditions and scavengers of free radicals inhibit or retard the formation of AGE and crosslinking of collagen. It is also known that the scavengers of free radicals are important in protecting the epidermis from damage by free radicals generated by both environmental and endogenous factors (Pugliese P.T., Dermatol. Nurs (1998) Dec: 10 (6): 401-16; quiz 41718).

Leather, which has a high differencirovany the Yu and undoubtedly complex organizational structure, is particularly susceptible to free radical damage because it is in contact with oxygen and other environmental stimuli (V. Calabrese, G. Scapagnini et. al., Drugs Exp.Clin. Res. (1999); 25 (6): 281-7). Studies have confirmed that UV radiation increases the formation of AGE on collagen, elastin and other proteins of the skin. This forms a vicious cycle due to the increase of accumulation of AGE on the skin and increase the production of singlet oxygen and peroxy radicals, which damage skin protein.

In recent years there has been considerable progress in clarifying the mechanisms underlying the aging. Recently revealed the induction of matrix metalloproteinases in the activation of activator protein (AP)-1 and nuclear factor (NF)-kB, as well as mutations of mitochondrial DNA (Berneburg M, et. al. Photodermatol Photoimmunol. Photomed (2000) Dec: 16 (6): 238-44). Early glycosylation condensation of reducing sugars, such as glucose, amino groups of proteins generates under the action of ultraviolet radiation photogenerated free radicals singlet oxygen. It is reported that AGE is an important factor promoting photoaging in the skin by generating active oxygen species, including O2-N2About2and HE (H. Masaki et. al., Biochem Biophys. Res. Commun (1997) Ju 18: 235). Based on in vitro studies of fibroblasts suggests possible mechanism in which AGE under the action of ultraviolet radiation And generates active oxygen species, including O2-N2About2and-HE-HE-particle plays a dangerous role in the promotion of cell damage (Hitoshi Masaki et. al. Biochemica et Biophysica Acta 1428 (1999), 45-56). Such radicals disrupt the natural balance of the skin, stimulating the skin cells to synthesize metalloproteinases. Metalloproteinase enzymes destroy collagen, not synthesizing anti-metalloproteinase, which inhibit the degradation of protein in the skin, which is a normal biological response. Unbalanced production metalloproteinase about anti-metalloproteinase induced singlet oxygen free radicals, leads to the destruction of collagen and elastin of the skin. This is followed by an incomplete healing of damaged collagen matrix and accumulation providermessage material, and as a result, sagging skin and wrinkles.

Due to the effect of AGE ultraviolet And radiation generating peroxide anion becomes high. This is done through the cell chain of electron transfer, in which UV-AGE energy increases the passage of electrons on the oxygen mainly condition is. This leads to increased formation of peroxide anion during the synthesis of adenosine triphosphate (ATP). The enzyme peroxide dismutase converts the peroxide anion into hydrogen peroxide and oxygen. Finally, the catalytic action of iron and copper converts the hydrogen peroxide into toxic hydroxyl radicals, causing damage to collagen and elastin of the skin with consequent defective wound healing and the development of solar scars that cause photoaging of the skin.

Shelves cosmetic market is filled with products for the treatment of external aging, but there is still a need in the products, the purpose of which is treatment of intrinsic aging by AGE inhibition in supporting the skin proteins.

The ability to inhibit the formation of end products increased glycosylation (supports the skin proteins such as collagen), along with AGE-destroying activity and activity removal of free radicals provides significant results in the treatment of aging skin and wrinkles, etc.

Thus, by using molecules that can change the presence of AGE, you can prevent the signs of aging skin and wrinkles, etc. and can be used for cosmetic applications.

Experience shows that aging skin and wrinkles occur despite good care of Ojai. Therefore, there is a need to develop an agent for prevention or treatment of skin aging caused by the formation of AGE. Compounds of the present invention are non-peptide, is able to modify the AGE structuring occurring in collagen and elastin. Compounds of the present invention can be introduced into the cosmetic composition of the drug with other agents.

To prevent or slow the formation of wrinkles on the skin is important to inhibit the formation of AGE, to destroy already formed AGE, and reduce oxidative stress by antioxidants or scavengers of free radicals. Essentially, the molecule that inhibits AGE, disrupts and slows the formation of AGE and prevents collagen breakdown, would be an ideal candidate for cosmetic purposes. Molecules of the present invention exhibit properties of AGE inhibitor and an effective destroyer of AGE, as well as scavenger of free radicals, making them most suitable for cosmetic applications.

Free radicals are atoms or molecules that have an atomic structure one or more unpaired electrons and are highly reactive. Free radicals - highly reactive species of oxygen (ROS)are produced continuously in si is the subject of a mammal as a result of normal metabolic processes. Exogenous sources of ROS include exercise, pollution (especially cigarette smoke and exhaust fumes of cars, alcohol, sunlight and medicines (such as anesthetics). Although free radicals play an important role in normal physiological mechanisms, excessive production of ROS leads to oxidative stress is a term usually used to refer to the result of oxidative damage to biologically important molecules such as proteins, fats and nucleic acids. It has long been known that proteins are susceptible to oxidation under the action of ROS. Particularly vulnerable aromatic amino acids such as cysteine and disulfide bonds. All biological substances contain a lot of polyunsaturated fatty acids, which are located mainly in the membrane lipids. They vysokorazvityh damage under the action of ROS.

A group of compounds known as antioxidants (also referred to as "scavengers of free radicals"), is the primary protection against oxidative stress. Such compounds function as protection membrane and cytosolic components from damage by ROS. The most important antioxidants that prevent the formation of new varieties radicals include enzyme systems such as superoxide dismutase (SOD) and glutathione peroxidase (GSH Px). Staroste the military antioxidants catch varieties radicals, thus preventing the chain reaction, and are nutritional supplements, such as vitamin E, vitamin C, taurine and b-carotene. The final line of antioxidant protection is provided by recovery systems, such as the enzyme methionine sulfoxide reductase that generates methionine residues in oxidized proteins and restores their function.

It is assumed that endogenous oxidative damage to cellular components, primarily proteins, lipids and DNA, contributes to the pathogenesis of many chronic diseases. It is now well confirmed the link between impaired antioxidant status, indices of oxidative damage and painful clinical conditions, such as diabetes, asthma, chronic renal failure, hepatitis, colitis, atopic dermatitis, arthritis, and various degenerative disorders. There is essentially dependent on the circumstances of the proof linking the reduced antioxidant status, including enzymatic and non-enzymatic scavengers, with increased oxidative damage and disease severity.

There is a need for molecules possessing the ability to destroy/to inhibit the formation of structured proteins in addition to having antioxidant activity, so that, in addition to their when the change in the number of diseases, the pathogenesis of which oxidative stress plays a fundamental role, they can be effective for cosmetic applications, which are noted below:

(a) smoothing and preventing the formation of wrinkles,

b) smoothing and preventing the formation of facial wrinkles,

c) promotion of growth of the epidermis,

d) fotosesija skin,

e) rehabilitation and prevention of discoloration of the skin,

f) removing and preventing the formation of age spots,

(g) air conditioning and prevention of dry skin,

h) removal and prevention of traces of suspenders,

i) the removal and prevention of skin imperfections,

(j) the care of the skin and maintaining its healthy condition,

k) the recovery and prevention of senile xerosis,

l) skin care and prevention of sunburn,

m) the prevention and recovery of loss of collagen,

n) improvement in skin texture,

o) improved skin tone,

p a thicker skin,

q) the reduction of pore size,

r) restoration of skin luster,

s) minimizes signs of fatigue,

t) the decrease in coal-fired rash,

w) the treatment of telangiectasias and

v) improving the aesthetic appearance of hair and nails.

Pharmaceutical application properties absorption of free radicals (antioxidant properties) molecules

In addition ispolzovania.pri for cosmetic applications based on their AGE-destructive/AGE-inhibiting and removing free radicals activity is the last activity of such compounds can be used in the strategy, aimed at combating oxidative stress for effective regulation discussed further diseases.

Neurodegenerative diseases such as Alzheimer's disease (A. D.), Parkinson's disease (P. D.), Huntington's disease (H. D.), motor neuron disease (M. N. D.), a prion disease

As people get older, they have reduced levels of antioxidants, and these low levels are directly linked with many diseases associated with aging, such as Alzheimer's and Parkinson's disease. One of the leading hypotheses is that oxidative stress induced sister oxygen special varieties of radicals (ROS)that damage the essential components of neurons, leading ultimately to the death of the neuron. Oxidative stress is included in many different events leading to neuronal damage, including an increase in the stiffness of the membrane, cleavage of the DNA chain and the deterioration of the absorption of glucose. Well identified several potential sources of oxidative stress in various neurodegenerative disorders [Munch G., et al., 1998].

In Alzheimer's disease for violation of redox balance are responsible mitochondrial dysfunction-mediated beta-amyloid processes, accumulation of transition metals and g the kinetic factors [Smith M.A., et al. 2000].

It is known that point mutations in superoxiddismutase enzymes are hereditary form of motor neuron disease.

Disturbances in the energy metabolism of neurons involved in the mechanism of Huntington's disease [S.E. Browne, et al., 1999].

Diabetes and diabetic vascular complications (DVCs)

Case of oxidative stress in diabetes is still not fully understood, but it is assumed that it occurs due to mitochondrial dysfunction, direct inhibition of the enzyme by hyperglycemia, autocrine glucose and activation of nicotinamide-adenine-dinucleotide(NADPH)oxidase. Oxidative stress in diabetes also increases due to the weak protection by reducing endogenous antioxidants. Oxidative stress is manifested in the form of higher concentrations of products of perechisleniya fats, fragility of red blood cells and decrease of antioxidant enzyme systems (CAT, GSH Px, SOD). Recent studies have also shown a positive correlation between the concentration of glucose in blood and induced oxidant DNA damage of lymphocytes [E. J. Harper. The 24th Annual WALTHAM®/OSU SYMPOSIUM].

ROS are generated during the oxidation of glucose and formation of the final products increased glycosylation (AGE). Accumulated data indicate that the generation of ROS plays an important role in the development of the AI (DVCs). Many biochemical pathway associated with hyperglycemia such as increased glycosylation, oxidation of glucose and polyol as one path, can increase the production of free radicals.

Hyperglycemia in diabetic patients leads to excessive autocycling glucose and consequently to the reduction of molecular oxygen and the formation of oxidized intermediates, such as peroxide ions (O2-), hydroxyl radicals (OH) and hydrogen peroxide (H2About2). Free radicals accelerate the formation of the final products increased glycosylation (AGE), because during the glycosylation occur, fragmentation and conformational changes, and it is shown that the oxidation of glucose depends on free radicals. In turn, AGE delivers even more free radicals; this process ends as oxidative glycosylation or glycoamylase. These free radicals interfere with vascular relaxation by deaktivirovana or quenching of nitric oxide (NO) and also gizatulina affect endothelial function. Also offered evidence that the reaction of Maillard (Maillard) acts as an amplifier of oxidative damage during aging and diabetes [D. Guigliano et al., 1996].

Intestinal diseases

Oxidizing the tress is an important case of tissue damage, which occurs when inflammation and ischemia. Intestinal ischemia, radiation enteritis, inflammatory bowel disease and promotion of gastric cancer and colorectal represent some gastrointestinal painful condition, the pathogenesis of which involved oxidative stress.

Liver disease

Alcoholic liver disease. Ethanol induces the increase in perechislenie fats or by increasing ROS or decrease in the level of endogenous antioxidants. Ethanol also induces many enzymes cytochrome P450 in microsomes and xanthine oxidase in the cytosol. The role of these enzymes in the generation of oxidative stress is well established in various studies [Ishii H., et al., 1997].

Chronic hepatitis C

Increased oxidative stress initiates fibrogenesis in the liver of patients with chronic hepatitis C. there is evidence confirming the path of oxidative stress, leading to active fibrogenesis in chronic hepatitis C. Such fibrogenic cascade characteristic of severe hepatitis C (e.g., oxidative stress, induction of c-myb, activation of stellate neurons and expression of the collagen gene), stimulated ROS.

Cancer

Oxidative DNA damage is a result of the interaction of DNA with ROS, in particular with hydroxyl radicals. Hydroxy is performance communications radicals produce many modifications of DNA. Oxidative attack HE radical on deoxyribose fragment leads to the release of free bases from DNA, generating the splitting circuits with different modifications of sugars and simple non-core (AR) sites.

ROS also interact and modify cellular proteins, lipids and DNA, which leads to changes in the functions of the target cells. The accumulation of oxidative damage is involved in both acute and chronic damage to cells, including possible participation in the formation of cancer. Acute oxidative damage can lead to death of the chosen cell and a compensatory increase in cell proliferation. Such a stimulus may lead to the formation of newly initiated precancerous cells and/or enhance the selective expansion of a clone of latent initiated precancerous cells. Similarly, acute sublethal oxidative damage can produce unrepaired DNA damage and lead to the formation of new mutations and, potentially, to the newly initiated cells. Therefore, ROS can exert multiple effects on the initiation stage of carcinogenesis by mediating activation of the carcinogen, causing damage to DNA and interfering with the recovery of damaged DNA.

Intensively investigated the use of various antioxidants to prevent and treat the following VI is s cancer.

1. Cancer of the lungs.

2. Cancer of the colon and rectum.

3. Cancer of the cervix.

4. Cancer of the breast.

5. Malignant melanoma.

Oxidative stress in heart disease

It is assumed that high levels of nutrients-antioxidants for life is to guard against the development of heart disease. It is shown that high doses of antioxidants within one month after an acute heart attack significantly reduce the number of deaths and the degree of heart damage in non-fatal cases.

Now suppose that the increase of oxidative stress is involved in the pathophysiology of endothelial dysfunction that accompanies a number of cardiovascular risk factors, including hypercholesterinemia, hypertension, and cigarette Smoking. It also plays a major role in the development of painful clinical conditions such as atherosclerosis and heart failure. Oxidative stress can activate redox-sensitive kinase cascades and transcription factors such as NFKB and AP-1, with the advent of growth factors expression associated with inflammatory response and cell proliferation. There are three enzyme systems that produce reactive species of oxygen in the vessel wall: NADH/NADPH (nicotinamide-adenine-dinucleotide of no the config/nicotinamide-adenine-dinucleotide restored) oxidase, xanthine oxidoreductase and endothelial oxygastra synthase (Zalba G. et. al., 2000, M.E. Rosenfeld, 1998).

Atherogenesis is seen as the result of interactions between multiple stimuli. Endothelial dysfunction plays a key role in the development of atherosclerosis. Elevated concentrations of homocysteine are associated with rapid onset of endothelial dysfunction, which represents another mechanism by which increased oxidative stress contributes to atherosclerosis. Oxidation of low density lipoprotein plays a role in several stages of atherogenesis. Oxidative stress also deactivates NFKB, which induces the expression of genes controlling the expression of cytokine and adhesion of leukocytes to the vessel wall (Maxwell, et al., 1997).

Animal studies have confirmed the assumption that free radicals can promote thrombosis, directly damaging the cells of blood vessels and other tissues and to intervene in vasomotor regulation with clinical consequences in the form of myocardial infarction and ischemic stroke.

In tissues where oxygen resources are used after ischemia, as in myocardial ischemia, the enzyme xanthine oxidase is changed into a form that is able to restore oxygen to natercia. When you use oxygen, for example, when reperfusion occurs, the flash generate the free radicals. ROS are formed at very high speed in post-ischemic myocardium. Thus, the biological damage by free radicals contributes to ischemic damage.

Apparently, oxidative stress is one of the mechanisms which can cause defects in the membranes and leading to intracellular calcium stress and dysfunction of cardiac contractions in the affected myocardium.

Macular degeneration and cataracts

Oxidative damage to the lens of the eye with age makes a major contribution to the formation of cataracts. Macular degeneration is also recognized as a consequence of oxidative damage.

HIV-disease

Violation of the antioxidant system of protection was observed in various tissues of HIV-patients. Oxidative stress may contribute to several aspects of the pathogenesis of HIV disease, such as viral replication, inflammatory response and reduced proliferation of immune cells, loss of function of the immune system, apoptosis, chronic weight loss. Antioxidants can be proposed as a promising method of treatment of HIV patients.

Chronic obstructive pulmonary disease (COPD)

Changing the metabolism of glutathione in the lungs and alveolar widely recognized as the Central distinguishing feature of many vocal the positive pulmonary diseases, including (COPD). Such changes are the result of changes in gene expression of gamma-glutamylcysteine (Gamma-GCS), the rate determining enzyme in the synthesis of glutathione. Oxidative stress is involved in the pathogenesis of COPD, as it causes decontamination antiproteinase, damage to the epithelium of the respiratory tract, mucous hypersecretion, increased allocation of neutrophils into the lungs, the activation of the transcription factor and gene expression of proinflammatory mediators [MacNee W., et al. 2001].

Kidney disease

ROS are involved not only in the emergence of various forms of kidney disease, mainly in experimentally induced glomerulonephritis, but also in various forms of acute renal failure.

Asthma

Although the pathogenesis of asthma is not fully specified, its typical feature is the increase in the number of inflammatory cells in the lung. These cells generate ROS in the pathophysiology of asthma, including the reduction of smooth muscles of the Airways, increased reactivity dichelonyx ways and increased vascular permeability.

The effect of the antioxidant status on immunological function.

The immune system is particularly sensitive to oxidative stress, primarily because immune cells are highly dependent on funds soundenabled-to-cell for effective functioning. The formation of peroxide compounds violates the integrity of the membrane and disrupts intracellular signal transmission.

Cataract

Oxidative damage of the eye lens with increasing age is a major contributor to the formation of cataracts.

Thus, by removing free radicals can adjust the following diseases:

1) Neurodegenerative diseases

(a) Alzheimer's Disease

(b) Parkinson's Disease

(c) Huntington's Disease

(d) motor neuron Disease

(e) a prion Disease

2) Diabetes and vascular complications in diabetes

3) Intestinal diseases

(a) Ischemia of the intestine

(b) Radiation enteritis

(c) Inflammatory bowel disease

(d) Cancer of the stomach and colon and rectum

4) liver Disease

(a) Alcoholic liver disease

(b) Chronic hepatitis C

5) Cancer

(a) lung Cancer

(b) Cancer of the colon and rectum

(c) cervical Cancer

(d) breast Cancer

(e) Malignant melanoma

6) Heart disease

(a) Atherosclerosis

(b) myocardial infarction

(c) Ischemic stroke

(d) Endothelial dysfunction

7) Ophthalmic diseases

(a) Formation of cataracts

(b) macular Degeneration

8) HIV disease

9) diseases of the respiratory tract

(a) Chronic and safety Deposit box is ActiveE lung disease (COPD)

(b) Asthma

10) kidney Disease

(a) acute glomerulonephritis

(b) Acute renal failure

SUMMARY of the INVENTION

The first objective of the present invention is the creation of a new class of five-membered heterocyclic compounds which can be used for the treatment of diabetes and age-related vascular complications and, in particular, for the treatment of complications of diabetes and other age-related diseases, such as vascular and neurovascular complications, including kidney disease, nerve damage, atherosclerosis, retinopathy, inflammatory diseases, immunological disorders, oxidative stress, and dermatological and cosmetic indications. In the scope of the invention also includes a method of destruction changes the color of teeth resulting from nonenzymatic appearance of a brown color in the oral cavity, the method includes introducing a quantity effective for the destruction of previously formed staple products with advanced glycosylation.

The second objective of the present invention is the creation of a five-membered heterocyclic compounds, which have a destructive AGE and inhibitory activities.

A third objective of the present invention is to develop a method of obtaining a five-membered heterocyclic compounds which oblad who have AGE-destructive and inhibiting activities.

The fourth object of the invention is the development of pharmaceutical compositions of a new class of five-membered heterocyclic compounds according to the invention and their pharmaceutically acceptable salts in combination with suitable carriers, solvents, excipients and other media commonly used for such compositions.

The fifth object of the invention is to develop a method of treatment of a diabetic patient by administration of compounds according to the invention either by themselves or in combination in drugs for antidiabetic therapy, or their salts, in a mixture with a pharmaceutically acceptable carrier, diluent, excipients, carriers, or other environments that may be suitable for these purposes.

The sixth object of the invention is to develop a new class of compounds, the same molecule which has a) activity removal of free radicals, (b) the activity of destruction AGE and AGE-inhibiting activity.

The seventh objective of the invention to provide cosmetic compositions comprising these compounds as active ingredients.

The eighth objective of the invention is to provide a method of producing cosmetic compositions.

The ninth objective of the invention is to develop a method cosmetic use by noisenakautomatically compositions according to the invention.

The tenth objective of the invention is to provide pharmaceutical compositions useful for removing free radicals from the cells of the body.

The eleventh objective of the invention is to develop a method of removing free radicals from the body cells of a mammal.

The twelfth objective of the invention is to develop a method of treatment of diseases caused by accumulation of free radicals in the body cells of a mammal.

The thirteenth object of the invention is to provide a method for inhibiting AGE and composition for inhibition of AGE of the mammal.

Another objective of the invention is to provide a fluid for dialysis, useful for peritoneal dialysis patient diabetic.

The invention also relates to a method of cosmetic treatment by applying the above composition. The invention additionally relates to pharmaceutical compositions useful for removing free radicals from the body cells of a mammal, which includes the connection defined above or its pharmaceutically acceptable salt in a mixture with a pharmaceutically acceptable carrier, diluent, excipient or solvent.

In addition, the invention relates to a method of removing free radicals from the body cells of a mammal by introducing a pharmaceutical composition, as noted is use, or treatment of diseases caused by accumulation of free radicals, by introducing a specified composition.

Additionally, the invention relates to a method for inhibiting AGE and composition for inhibition of AGE using the compounds of the invention.

DETAILED description of the INVENTION

The present invention relates to a new class of compounds, ceasing AGE, of the formula I

R1represents an alkyl or aryl group;

Y is selected from the group comprising sulfur, oxygen, nitrogen, and alkyl;

A and B are independently selected from the group comprising nitrogen, sulfur, oxygen or carbon with the formation of heteroaromatic ring system;

R2, R3and R4independently selected from the group comprising F, Cl, Br, I, OR7, NO2, alkyl, aryl, including heteroaryl, formyl, acyl, C(O)NR6R7C(O)OR6, NR6R7N=C(R6)(R7), SR6, SO2NH2, SO2alkyl and SO2aryl; R2, R3and R4optional can be linked together with the formation of the ring system;

If the connection quaternion, R5independently selected from the group comprising alkyl and aryl; if the connection is not quaternion, R5absent and X is absent;

R6independently selected from the group comprising H, alkyl and ar is l, including heteroaryl, provided that R6may vary for R2, R3and R4in the same connection;

R7independently selected from the group comprising H, alkyl and aryl, including heteroaryl, and in each case optional differs from the substituent R6provided that R7may vary for R2, R3and R4in the same connection,

If the connection quaternion, X is selected from the group comprising halide ion, acetate ion, perchlorate ion, sulfonate ion, oxalate ion, citrate ion, tosylate-ion, maleate ion, mesylate, ion, carbonate ion, sulfite ion, hydropoetry ion, phosphonate ion, phosphate ion, BF4-PF6-,

Provided that when two alkyl groups are present on the same carbon atom or nitrogen, they are not necessarily linked together with the formation of a cyclic structure.

As used herein, the term "alkyl" refers to optionally substituted hydrocarbon group associated simple carbon-carbon bonds and having from 1 to 8 carbon atoms linked together. Alkyl hydrocarbon group may be linear, branched or cyclic, saturated or unsaturated. Substituents selected from F, Cl, Br, I, N, S, O, and aryl. Preferably there are not more than three deputies.

As IP is alzavano in this description, the term "aryl" refers to optionally substituted aromatic group having at least one ring having a conjugated PI-electron system, and containing up to two conjugated or condensed ring systems. Aryl includes carbocyclic aryl, heterocyclic aryl and bizarrerie group, all of which optionally can be substituted. Substituents selected from F, Cl, Br, I, N, S, O, and linear or branched C1-C6the hydrocarbon.

In a preferred embodiment, the invention relates to a new class of compounds of formula (1), destructive AGE, inhibiting AGE and removes free radicals, and their pharmaceutically or cosmetically acceptable salts

where

R1selected from linear or branched (C1-C12) alkyl, (C2-C12) alkenyl, (C3-C7) cycloalkyl, (C5-C7) cycloalkenyl, bicycloalkyl, bicycloalkyl, geterotsiklicheskie, aryl, aralkyl, heteroaryl, heteroalkyl, and where one or more heteroatoms, when they are present, are independently selected from O, N or S, and optionally substituted, where the substituents are selected from the first group comprising halogen, hydroxy, nitro, cyano, amino, oxo and the oxime, or from a second group including linear or branched (C1-C 8)alkyl, (C3-C7)cycloalkyl, alkylsilanes, perhalogenated, perhalogenated, aryl, aralkyl, alkylaryl, alkylether, alcoxialchil, perhalogenated, alkylchlorosilanes, geterotsiklicheskikh, perhalogenatedonly, heteroaryl, heteroalkyl, alkylaryl, perhalogenated, acyl, alkoxyalkyl, thioalkyl and tiari, where deputies from the specified second group optionally substituted by R10and optionally and independently associated with -(CO)O-, -(CO)NH-, -NH-, -NR8-, -O-, -S-, -(SO)-, -(SO2), -(SO2)NH-, or-NH(CO)-;

Y is absent or selected from the group comprising (C1-C12)alkyl-Z, or (C2-C12)alkyl, where Z is selected from sulfur, oxygen or nitrogen;

A and B are independently selected from NH, NR6, sulfur, oxygen or carbon with the formation of heteroaromatic ring system;

R2, R3and R4independently selected from the first group, including hydrogen, halogen, NO2N=C(R8)(R9), -NR8R9, -OR8perhalogenated, -(CO)NR8R9, -(CO)R8, -(CO)OR8, -O(CO)R8, -NH(CO)R8or from the second group including linear or branched (C1-C12)alkyl, (C2-C12)alkenyl, (C3-C7)cycloalkyl, (C5-C7)cycloalkenyl, bicycloalkyl, bicycloalkyl, heteroseksualci, aryl, aralkyl, heteroaryl is, heteroalkyl, where one or more members of this second group, when they are present, optionally substituted R10and where one or more heteroatoms, when they are present, are independently selected from O, N, or S;

R5absent or selected from the group including linear or branched (C1-C12)alkyl, (C2-C12)alkenyl, (C3-C7)cycloalkyl, (C5-C7)cycloalkenyl, bicycloalkyl; CH2(CO)R7CH2(CO)other8CH2(CO)NR8R9and CH2(CO)OR7that is not necessarily replaced by R10;

R6and R7independently selected from the group including linear or branched (C1-C8)alkyl, (C3-C7)cycloalkyl, alkylsilanes, perhalogenated, perhalogenated, aryl, aralkyl, alkylaryl, alkylglycerol, alcoxialchil, perhalogenated, alkylchlorosilanes, geterotsiklicheskikh, perhalogenatedonly, heteroaryl, heteroalkyl, alkylaryl, perhalogenated, acyl, benzoyl, alkoxyalkyl, thioalkyl and tiari, where members of the specified group optionally substituted by R10;

R8and R9independently selected from the group including linear or branched (C1-C12)alkyl, alkoxyaryl, alkoxyalkyl, alkoxyalkyl, alkoxyaryl, perhalogenated, (C2-C1 )alkenyl, (C3-C7)cycloalkyl, perhalogenated, allogeneically, cyanoethylated, bangalorepethospital.com, (C5-C7)cycloalkenyl, bicycloalkyl, bicycloalkyl, heteroseksualci, aryl, aralkyl, heteroaryl, heteroalkyl, perhalogenated, perhalogenated, where the substituents specified group optionally substituted by R10;

R10selected from halogen, hydroxy, nitro, cyano, amino, oxo, perhalogenated (C1-C6or oxime;

X is selected from the group comprising halide ion, acetate ion, perchlorate ion, sulfonate ion, oxalate ion, citrate ion, tosylate-ion, maleate ion, mesylate, ion, carbonate ion, sulfite ion, hydropoetry ion, phosphonate ion, phosphate ion, BF4-PF6-,

provided that, when the groups/substituents are present in the same or adjacent carbon atoms or nitrogen, they do not necessarily together may form a five, or six, or semiline ring, optionally containing one or more double bonds and optionally containing one or more heteroatoms selected from O, N, or S.

It should be understood that the compounds of formula (1), as defined above, include their analogs, their tautomeric forms, their stereoisomers, their polymorphs, their pharmaceutically priemlemye the solvate and their cosmetically reception is administered a solvate.

Non-limiting examples of pharmaceutically/cosmetically acceptable salts of the compounds according to the invention include, but are not ogranichivayutsya this salt fragment carboxylic acids, such as alkali metal salts, such as salts of Li, Na and K; salts of alkaline-earth metals, such as salts of CA and Mg; salts of organic bases, for example, lysine, arginine, guanidine, diethanolamine, choline, and the like; ammonium salts or substituted ammonium and aluminium salts; salts can be an acid additive salts, such as sulfates, nitrates, phosphates, perchlorates, borates, hydrogenogenic, acetates, tartratami, maleate, citrates, succinate, palmoate, methansulfonate, benzoate, salicylates, hydroxynaphthoate, bansilalpet, ascorbate, glycerophosphate, ketoglutarates and the like.

These new connections are only offered as examples illustrative of the compounds of General formula I, as defined above, and in no way limit the invention:

a) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium (Compound 1);

b) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(3-phenylmethyl)oxazol-5-yl]pyridinium (Compound 2);

c) dibromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[3-{1-(2-Tien-2'-yl)-2-oxoethyl)pyridine-4-thio}methyl-pyrazole-5-yl]pyridinium (Compound 3);

d) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[3-{1-(3,5-dimethylpyrazol-1-yl)shall ethyl}pyrazole-5-yl]pyridinium (Compound 4);

e) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[3-phenylmethyl}-1-{2-pyridyl}pyrazole-5-yl]pyridinium (Compound 5);

f) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[3-{(3,5-dimethylpyrazol-1-yl)methyl-1-pyridyl}pyrazole-5-yl]pyridinium (Compound 6);

g) bromide 1-[2-(cyclopropylamino)-2-oxoethyl]-3-[3-{(3,5-dimethylpyrazol-1-yl)methyl}pyrazole-5-yl]pyridinium (Compound 7);

h) bromide 1-{2-(4-nitro-2-thienyl)-2-oxoethyl}-3-[3{(3,5-dimethylpyrazol-1-yl)methyl}pyrazole-5-yl]pyridinium (Compound 8);

i) chloride 1-(2-cyclopropylamino-2-oxoethyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium (Compound 9);

j) dibromide 3,5-bis-[1-(2-Tien-2'-yl-2-oxoethyl)pyridine-3-yl]pyrazole (Compound 10);

k) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(1-phenyl-3-phenylmethyl)pyrazole-5-yl]pyridinium (Compound 11);

l) chloride 1-(2-(5'-methyl-2-thienyl)-2-oxoethyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium (Compound 12);

m) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[1-phenyl-3-{(3,5-dimethyl pyrazole-1-yl)methyl)}pyrazole-5-yl]pyridinium (Compound 13);

n) bromide 1-(2-phenyl-2-oxoethyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium (Compound 14);

o) chloride 1-(2-cyclopropylamino-2-oxoethyl)-3-[(1-phenyl-3-phenylmethyl)pyrazole-5-yl]pyridinium (Compound 15);

p) bromide 1-(2-(4-benzyl-l-piperidinyl)-2-oxoethyl)-3-[(3-phenoxymethyl)pyrazole-5-yl]pyridinium (Compound 16);

q) chloride 1-(2-phenyl-2-oxoethyl)-3-[(3-(3,5-dimethylpyrazol-1-yl)methyl)pyrazole-5-yl]pyridinium (Compound 7);

r) chloride 1-(2-(5-methyl-2-thienyl)-2-oxoethyl)-3-[(3-(3,5-dimethylpyrazol-1-yl)methyl)pyrazole-5-yl]pyridinium (Compound 18);

C) chloride 1-(2-phenyl-2-oxoethyl)-3-[(1-phenyl-3-phenylmethyl)pyrazole-5-yl]pyridinium (Compound 19);

t) chloride 1-(2-(5-methyl-2-thienyl)-2-oxoethyl)-3-[(3-(2-cyclohexylethyl)pyrazole-5-yl]pyridinium (Compound 20);

u) chloride 1-(2-cyclopropylamino-2-oxoethyl)-3-[(3-(2-cyclohexylethyl)pyrazole-5-yl]pyridinium (Compound 21);

v) chloride 1-(2-phenyl-2-oxoethyl)-3-[(3-(2-cyclohexylethyl)pyrazole-5-yl]pyridinium (Compound 22);

w) chloride 1-(2-cyclopropylamino-2-oxoethyl)-3-[(1-cyclohexyl-3-phenylmethyl)pyrazole-5-yl]pyridinium (Compound 23);

x) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(3-phenoxymethyl)pyrazole-5-yl]pyridinium (Compound 24);

y) chloride 1-[2-(l-adamantylamine)-2-oxoethyl]-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium (Compound 25);

z) bromide 1-(2-phenyl-2-oxoethyl)-3-[{3-(3,5-dimethylpyrazol-1-yl)methyl)}-1-phenylpyrazol-5-yl]pyridinium (Compound 26);

aa) bromide 1-(2-(4-nitro-2-thienyl)-2-oxoethyl)-3-[(1-cyclohexyl-3-(3,5-dimethylpyrazol-1-yl)methyl)pyrazole-5-yl]pyridinium (Compound 27);

bb) bromide 1-(2-(4-nitro-2-thienyl)-2-oxoethyl)-3-[(3-(2-cyclohexylethyl)pyrazole-5-yl]pyridinium (Compound 28);

cc) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(1-phenyl-3-phenoxymethyl)pyrazole-5-yl]pyridinium (Compound 29);

dd) bromide 1-(2-(4-nitro-2-thienyl)-2-oxoethyl)-3-[(1-phenyl-3-phenylmethyl)pyrazole-5-the l]pyridinium (Compound 30);

ee) chloride pyrazole-1-(2-cyclopropylamino-2-oxoethyl)-3-[(3-phenoxymethyl)pyrazole-5-yl]pyridinium (Compound 31);

ff) chloride 1-(2-cyclopropylamino-2-oxoethyl)-3-[(1-cyclohexyl-3-(3,5-dimethylpyrazol)-1-yl)-5-yl]pyridinium (Compound 32);

gg) bromide 1-(2-(5-chloro-2-thienyl)-2-oxoethyl)-3-[(3-phenoxymethyl)pyrazole-5-yl]pyridinium (Compound 33);

hh) chloride 1-(2-phenyl-2-oxoethyl)-3-[(1-phenyl-3-phenoxymethyl)pyrazole-5-yl]pyridinium (Compound 34);

ii) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(1-cyclohexyl-3-(3,5-dimethylpyrazol-1-yl-methyl)pyrazole-5-yl]pyridinium (Compound 35);

jj) bromide 1-(2-cyclopropylamino-2-oxoethyl)-3-[(1-phenyl-3-phenoxymethyl)pyrazole-5-yl]pyridinium (Compound 36);

kk) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(1-phenyl-3-(2-cyclohexylethyl)pyrazole-5-yl]pyridinium (Compound 37);

ll) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(1-cyclohexyl-3-phenoxymethyl)pyrazole-5-yl]pyridinium (Compound 38);

mm) of the hydrochloride of 3-[(3-phenylmethyl)pyrazole-5-yl]pyridine (Compound 39);

nn) of the hydrochloride of 3-[(3-phenoxymethyl)pyrazole-5-yl]pyridine (Compound 40);

oo) 3-[(3,5-dimethylpyrazol-1-yl-methyl)pyrazole-5-yl]pyridine (Compound 41);

pp) 3-[3-(2-cyclohexylethyl)-pyrazole-5-yl]pyridine (Compound 42);

qq) bromide 1-(2-naphthyl-2-oxoethyl)-3-[(3-phenoxymethyl)pyrazole-5-yl]pyridinium (Compound 43);

rr) chloride 1-(phenylmethyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium (Compound 44);

ss) chloride 1-(2-tie the -2'-yl-2-oxoethyl)-3-[(3-(1-naphthyl)pyrazole-5-yl]pyridinium (Compound 45);

tt) chloride 1-(2-phenyl-2-oxoethyl)-3-[3-(thienyl-2-yl-methyl)pyrazole-5-yl]pyridinium (Compound 46);

uu) chloride 1-(2-(5-methyl-2-thienyl)-2-oxoethyl)-3-[3 (2-phenylethyl)pyrazole-5-yl]pyridinium (Compound 47);

vv) chloride 1-(2-(5-methyl-2-thienyl)-2-oxoethyl)-3-[3-(3-phenoxypropan)pyrazole-5-yl]pyridinium (Compound 48);

ww) bromide 1-(isopropyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium (Compound 49);

xx) chloride 1-(2-(5-methyl-2-thienyl)-2-oxoethyl)-3-[(3-thienylmethyl)pyrazole-5-yl]pyridinium (Compound 50);

yy) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(3-(N-methylindol-3-ylmethyl)pyrazole-5-yl]pyridinium (Compound 51);

zz) bromide 1-(2-naphthyl-2-oxoethyl)-3-[(3-methyl)pyrazole-5-yl]pyridinium (Compound 52);

aaa) chloride 1-(2-(1,4-benzodioxan-6-ylamino-2-oxoethyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium (Compound 53);

bbb) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(3-phenyl)pyrazole-5-yl]-5-bromopyridine (Compound 54);

ccc) chloride 1-(2-Tien-2'-yl)-2-oxoethyl)-3-[(3-phenyl)pyrazole-5-yl]chinoline (Compound 55) and

ddd) 3-[(3-phenyl)pyrazole-5-yl)]quinoline (Compound 56).

A reasonable list of substituents of the above compounds on cadinene General formula (I)as defined above, are presented in the following table.

Table 1
Conn.No.R1R2R3R4R5 ABYX
1PhenylHHH-CH2-C(O)-2-thienylNHN-CH2-Br
2PhenylHHH-CH2-C(O)-2-thienylAboutN-CH2-Br
3Structure (a)HHH-CH2-C(O)-2-thienylNHN-CH2-S-Br
4Structure (b)HHH-CH2-C(O)-2-thienylNHN-CH2-Br
5PhenylHHH-CH2-C(O)-2-thienylN-(2-pyridyl)N-CH2-Br
6Structure (b)HHH-CH2-C(O)-2-thienylN-(2-pyridyl)N-CH2-Br
7Structure (b)HH H-CH2-C(O)-NH(cyclopropyl)NHN-CH2-Cl
8Structure (b)HHH-CH2-C(O)-(5-nitro-2-thienyl)NHN-CH2-Br
9PhenylHHH-CH2-C(O)-NH(cyclopropyl)NHN-CH2-Cl
10Structure (C)HHH-CH2-C(O)-2-thienylNHNno-Br
11PhenylHHH-CH2-C(O)-2-thienylN-(phenyl)N-CH2-Cl
12PhenylHHH-CH2-C(O)-(5-methyl-Tien-2-yl)NHN-CH2-Cl
13Structure (b)HHH-CH2-C(O)-2-thienylN-(phenyl)N-CH2-Cl
14PhenylHHH-CH2-C(O)-phenylNHN-CH2-Br
15PhenylHHH-CH2-C(O)-NH(cyclopropyl)N-(phenyl)N-CH2-Cl

26
Conn.No.R1R2R3R4R5ABYX
16PhenylHHH-CH2-C(O)-(4-benzylpiperidine-1-yl)NHN-CH2-O--Cl
17Structure (b)HHH-CH2-C(O)-phenylNHN-CH2-Cl
18Structure (b)HHH-CH2-C(O)-(5-methyl-Tien-2-yl)NHN-CH2-Cl
19PhenylHHH-CH2-C(O)-f the Nile N-(phenyl)N-CH2-Cl
20CyclohexylHHH-CH2-C(O)-(5-methyl-Tien-2-yl)NHN-CH2-CH2-Cl
21CyclohexylHHH-CH2-C(O)-NH(cyclopropyl)NHN-CH2-CH2-Cl
22CyclohexylHHH-CH2-C(O)-phenylNHN-CH2-CH2-Cl
23PhenylHHH-CH2-C(O)-NH(cyclopropyl)N-(cyclohexyl)N-CH2-Cl
24PhenylHHH-CH2-C(O)-2-thienylNHN-CH2-About-Cl
25PhenylHHH-CH2-C(O)-NH-(1-substituted)NHN-CH2-About-Cl
Structure (b)HHH-CH2-C(O)-phenylN-phenylN-CH2-Br
27Structure (b)HHH-CH2-C(O)-(4-nitro-Tien-2-yl)N-(cyclohexyl)N-CH2-Br
28CyclohexylHHH-CH2-C(O)-(4-nitro-Tien-2-yl)NHN-CH2-CH2-Cl
29PhenylHHH-CH2-C(O)-2-thienylN-phenylN-CH2-About-Cl
30PhenylHHH-CH2-C(O)-(4-nitro-Tien-2-yl)N-phenylN-CH2-Br
31PhenylHHH-CH2-C(O)-NH(cyclopropyl)NHN-CH2-About-Cl
32Structure (b)HHH -CH2-C(O)-NH(cyclopropyl)N-(cyclohexyl)N-CH2-Cl
33PhenylHHH-CH2-C(O)-(5-chlortan-2-yl)NHN-CH2-About-Br
34PhenylHHH-CH2-C(O)-phenylN-phenylN-CH2-About-Cl
35Structure (b)HHH-CH2-C(O)-2-thienylN-(cyclohexyl)N-CH2-Cl
36PhenylHHH-CH2-C(O)-NH(cyclopropyl)N-phenylN-CH2-About-Cl

Conn.No.R1R2R3R4R5ABYX
37CyclohexylHHH-CH2-C(O)-2-thienylN-phenylN-CH2CH 2-Cl
38PhenylHHH-CH2-C(O)-2-thienylN-(cyclohexyl)N-CH2-About-Cl
39*PhenylHHHnoNHN-CH2-no
40PhenylHHHnoNHN-CH2-O-no
41Structure (b)HHHnoNHN-CH2-no
42CyclohexylHHHnoNHN-CH2-CH2-no
43PhenylHHH-CH2-C(O)-2-naphthylNHN-CH2-O--Br
44PhenylHHH-CH -phenylNHN-CH2-Cl
451-NafterHHH-CH2-C(O)-2-thienylNHN-CH2-Cl
462-ThienylHHH-CH2-C(O)-2-phenylNHN-CH2-Cl
47PhenylHHH-CH2-C(O)-(5-methyl-Tien-2-yl)NHN-CH2-CH2--Cl
48PhenylHHH-CH2-C(O)-(5-methyl-Tien-2-yl)NHN-CH2-CH2-CH2-O--Cl
49PhenylHHHIsopropylNHN-CH2-Br
50PhenylHHH-CH2-C(O)-(5-methyl-Tien-2-yl)NHN-CH2-S-Cl
511-Methyl-ind the l-3-yl HHH-CH2-C(O)-2-thienylNHN-CH2-Cl
52HHHH-CH2-C(O)-2-naphthylNHN-CH2-Br
53PhenylHHH-CH2-C(O)-NH-(3,4-atlanticcity)-NHN-CH2-Cl
54PhenylH5-BrH-CH2-C(O)-2-thienylNHNotsutstvuet-Cl
55PhenylHBenzene ring, condensed 5.5-position-CH2-C(O)-2-thienylNHNotsutstvuet-Cl

Conn.No.R1R2R3R4R5ABYX
56PhenylHBenzene ring, condensed 5.5-position the research Institute noNHNotsutstvuet-Cl

* allocated in the form of HCl salt

Structure (a)Structure (b)

In accordance with the embodiment of the present invention the compounds according to the present invention can be used for the treatment of diabetic complications and age-related vascular and neurovascular complications, including kidney disease, nerve damage, atherosclerosis, retinopathy, inflammatory diseases, immunological disorders, oxidative stress, and dermatological and cosmetic indications and discoloration of the teeth caused by elevated levels of previously formed AGE. Elevated levels previously educated AGE can be controlled by destroying/inhibiting products AGE using compounds specified in the invention.

The new compounds according to the invention of General formula I can be synthesized. One method of obtaining compounds is in the interaction of substituted/unsubstituted acetylpyridine with alkilirovanie esters in the presence of a suitable base. Then they are subjected to cyclization using different sinteticheskih ways. If necessary, can be carried out quaternization using a suitable reagent in an alcohol solvent such as methanol, ethanol, propanol, etc. and high-boiling solvents, such as toluene, xylene, or DMF, in the course of onset 6 to 48 hours to obtain the target compounds.

Examples of substituted derivatives of pyridine, which can be used to obtain specific compounds of the invention:

1. N,N'-bis(nicotinyl)hydrazine

2. 3-[(2-pyridyl)hydrazinecarboxamide]pyridine

3. 3-[2-methanesulfonyl)hydrazinecarboxamide]pyridine

4. 3-[(2-benzoyloxy)ethylaminomethyl]pyridine

5. 3-[(2-phenylsulfonyl)hydrazinecarboxamide]pyridine

6. 3-[(2-acetoxy)ethoxycarbonyl]pyridine

7. 3-[(2-benzoyloxy)ethoxycarbonyl]pyridine

8. 3-[(2-methoxy)ethoxycarbonyl]pyridine

9. 3-[(2-phenylenecarbonyl)hydrazinecarboxamide]pyridine

10. 3-[(2-acetoxy)ethylaminomethyl]pyridine

11. 3-[(2-(4-methylphenylpolysiloxane))]pyridine

12. 3-[(2-benzoyl)hydrazinecarboxamide]pyridine

13. 3-[(2-phenylmethanesulfonyl)hydrazinecarboxamide]pyridine

14. 3-[(2-(3-cyclohexylpropionic)hydrazinecarboxamide]pyridine

15. 3-[(2-methoxy)ethylaminomethyl]pyridine

16. 3-[1-oxo-1-(2-methoxycarbonyl)pyridyl]hydrazinopyridazine

Below are examples of quaternization agents that can be used in the reaction:

1. 2-romization

2. 2-chloracetamide

3. pencilvania

4. penicillanic

5. 2,4-dichlorophenylamino

6. N-phenylglycine

7. N-cyclopropylacetic

8. ethylbromoacetate

9. bromoacetophenone

10. N-isopropylacrylamide

11. N-chloroacetyl-2-pyrrolidinone

12. Chloroacetic acid

Screening in-vitro activity of fracture AGE

Example 1A

Education AGE in vitro, was investigated in the laboratory by incubating the reducing sugar glucose with protein - bovine serum albumin leads to the brown colour of the solution and the increase in fluorescence. Fluorescence was used as a criterion to control the increasing AGE of education.

Materials:

Bovine serum albumin (fraction V) (BSA)

Glucose, analytical quality

Buffered phosphate saline (PBS)

Equipment:

The microplate ELISA Reader (Spectramax Plus (Molecular Devices, USA)

Apparatus for washing microplate (Bio-Tec Instruments, USA)

PH meter

Methods experiment: Elisa (enzyme-linked immunosorbent assay)

160 mg/ml protein, bovine serum albumin, BSA and 1.6 M glucose sugar was dissolved in phosphate buffered saline, PBS. As a preservative was added sodium azide at a concentration of 0.02%. The solution is aseptically filtered through a 0.22 μm filter and kept the La aging at 37° With over 16 weeks. After 16 weeks, spent dialysis solution relative to PBS, divided into aliquots and kept at -20°C.

To determine the activity of destruction AGE of 10 ág/ml 16-week solution of AGE-BSA were incubated with various concentrations of the test compounds at 37°within 24 hours, and the activity of destruction AGE for the test compounds were determined using ELISA (enzyme-linked immunosorbent assay).

ELISA was carried out as follows:

1. Tablet for micrometrology covered as standard by different concentrations of the 16-week solution of AGE-BSA. Each concentration was applied in three sequences.

2. The test samples were coated tablet for micrometrology in concentrations from 5 ng to 20 ng per well in a threefold sequence.

3. Tablet incubated at 37°C for one hour.

4. After incubation the tablet were washed in PBST (PBS with 0.05% of Tween 20).

5. Were blocked using 5% skim milk at 37°C for one hour.

6. The tablet were washed in PBST.

7. Added primary antibody against AGE-BSA and the plate is incubated at 37°C for one hour.

8. The tablet were washed in PBST.

9. Added secondary conjugate anti-rabbit-HRPO (horseradish peroxidase) and the plate incubated at 37°C for one hour.

10. PL is het were washed in PBST.

11. Spent the improvement of dye using OPD (dihydrochloride of orthophenanthroline) and hydrogen peroxide.

12. Measured OD (optical density) at 450 nm read-620 nm reading) after incubation at 37°C for 15 minutes using a microplate reader Microplate ELISA.

The activity of destruction AGE of the compounds was determined by the following formula:

OP450-620Control OP450-620Test

% activity destruction = -------------------------- x 100

OP450-620Control

OP450-620Control = the Absorption of 20 ng AGE-BSA after incubation at 37°within 24 hours without test connection.

OP450-620Test = Absorption 20 ng AGE-BSA after incubation at 37°within 24 hours with the required concentration of test compounds.

Example 1B

Method based on gel chromatography.

Method based on gel chromatography was used to determine the activity of destruction AGE for connections.

Principle:

The separation method gel chromatography (GPC) depends on differences in size, more precisely, in the hydrodynamic volume of the protein in the sample. Molecules of larger size do not penetrate into the pores of the particles of the column and suiryudan in the free volume of the column (Vo). The pores of the particles of the column differential available for smaller particles, depending on their RA is a measure. This column call (Vi). The total available volume (Vt) represents the sum of the volume outside of the particles (Voand the volume available inside the particles (Vi)

Vt= Vo+ Vi

Therefore, in ordinary experience gel chromatography (GPC), high molecular weight molecules suiryudan with lower retention times, whereas molecules with a lower molecular weight are retained longer. The purpose of quantitative evaluation is logged area under the curve for the corresponding molecules. The same principle applies in vitro screening of molecules of the present invention.

Longevity highly crosslinked final products increased glycosylation (AGE) was obtained by incubation in vitro of bovine serum albumin (BSA) with glucose for 16 weeks. The molecular weight of BSA and AGE-BSA significantly differed on the GPC column, and, therefore, they were good separation. Reduction of the area of AGE-BSA, incubated in the presence of the destroyer of AGE, compared to control AGE-BSA (incubated in the absence of the destroyer AGE), made it possible to assess AGE-destroying activity of the drug. To test nonspecific activity of the molecule, a similar experiment was repeated with the BSA.

Methodology:

A known concentration of a 16-week AGE-BSA were incubated in risotti and in the absence of a pre-defined concentration of the drug at 37° C for 24 hours in a clean transparent glass tubes. Solution without drugs served as control and the solution containing the drug, were treated as test samples.

Helpanimals chromatography was performed on equal amounts of control of the preparation of AGE-BSA and mortar AGE-BSA-treated drug. Expected average square on two chromatograms.

In the chromatogram of the control and treated AGE-BSA samples was observed by two major peaks.

Peak I = high molecular weight peak

Peak II = low molecular weight peak

Peak I + Peak II = Total AGE-BSA

Calculations:

(The average area of peak I in the treated sample)

% destruction at the peak I = 100- ---------------- x 100

(The average area of peak I in the sample)

(The average area of peak II in the treated sample)

% destruction in peak II = 100- ---------------- x 100

(The average area of peak II in the sample)

(Average peak area I+ peak II in the treated sample)

% Of total destruction = 100----------------------------------X 100

(Average peak area I+ peak II in the sample)

Using illustrative of the compounds was calculated % destruction AGE, and the results are shown in table 2.

Table 2
Sample

(Compound No.)
Concentration (µm)% destruction
Connection 71,051,72
Compound 8585,31
Connection 115,076,84
Connection 121089,23
Connection 131081,05
The connection 141058,14
The connection 151080,03
The connection 161095,51
Connection 171052,27
The connection 185,052,97
Connection 191091,22
Connection 211093,43
The connection 2210100,00
The connection 231053,29
Connection 241097,72
The connection 25598,59
The connection 261042,37
Connection 271086,98
The connection 3110 45,72
The connection 3410100,0
The connection 351066,66
The connection 371085,45
The connection 401066,06

Thus, compounds 7, 8, 11-19, 21-25, 27, 34, 35, 37 and 40 have a very good AGE destructive activity, among which the effectiveness of compounds 8, 11-13, 15, 16, 19, 21, 22, 24, 25, 27, 34 and 37 has a much higher order.

AGE inhibiting activity of compounds

Further, taking into account the ability of the compounds of the present invention prevent the formation of AGE due to the described inhibitory effect, can be prevented or reduced the development of pathological conditions caused by AGE. The dual activity of compounds as agents that Deplete AGE, as well as an AGE inhibitor, makes them even more useful for diseases associated with age and diabetes complications, kidney disease, nerve damage, retinopathy, neuropathy, endothelial dysfunction, atherosclerosis, microangiopathy, darkening that occurs in the mouth similar to a darkening of the teeth, Alzheimer's disease, arterial compliance and compliance, restenosis, abnormal obstacles tissue in peritoneal dialysis erectile dysfunction and other kinds of dysfunction, the burden of AGE on the cage is very crucial. In fact, the triple action of compounds (a) as AGE-destroying agent, (b) AGE inhibitor, (C) scavenger of free radicals can be effectively used for the destruction or prevention of a number of pathological conditions, as well as for the destruction and prevention of the cosmetic aspects of aging.

Example 1C

The study of AGE-inhibiting activity

The following method was used to determine the inhibitory effect of the investigated compounds.

The following method was used to determine the inhibitory effect of these compounds in the reaction of Maillard in vitro. This method is a method taken from U.S. patent 5514676 and European patent 0339496A2.

Preparing a solution of bovine serum albumin (BSA), ribose and the compounds in phosphate buffered saline (PBS, pH 7,4) so that the final concentration of BSA and ribose was 10 mg/ml and 500 mm, respectively. The addition of the compound was carried out under aseptic conditions. Also in this solution was added sodium azide (0.02 percent) to prevent microbial growth. As a positive control were incubated separate tube containing BSA, ribose and sodium azide in the same concentrations and buffer, as described above, but the be is any of the investigated compounds. After incubation at 37°within 7 days of each sample was removed 40 microlitres and diluted PBS to a final concentration of BSA 1 mg/ml Fluorescence of all samples were measured at the maximum excitation of 355 nm and the maximum emission of 460 nm using fluorimetry f-MAX Fluorimeter (Molecular Device, USA). To study the effect of test compounds on the fluorescence of freshly prepared solutions of the compounds were mixed with pre-incubated with the positive control (i.e. BSA+ribose), so as to achieve the same concentration of all components in the sample.

The percentage of inhibition of the test compounds was measured in the following way:

F4-F3

% Inhibition = ------------- X 100

F4

Where F3 = Fluorescence of BSA + ribose + Connection

F4 represents the fluorescence of the incubated sample (BSA+ribose) + newly added test connection

Illustrative compounds of General formula (I) were tested for their activity as an AGE inhibitor, and the results are presented below in table 3.

Table 3
Connection # Concentration% inhibition

(7 day)
Connection 610 mm66
Soy is inania 10 2.5 mm75
Connection 111.25 mm32,9
Connection 1310 mm57
Connection 172.5 mm57,43
The connection 185 mm79
Connection 195 mm64,23
The connection 222.5 mm51
Connection 245 mm82,5
The connection 265 mm61,45
The connection 295 mm55,22
The connection 345 mm60
The connection 3510 mm73,8

Agents that Deplete AGE:

As shown in table 2, the compounds of the present invention can be used for the destruction of the AGE. Therefore, the compounds of the present invention can be used as a drug for the treatment of diabetic complications and age-related diseases caused by the accumulation of AGE. In addition, these compounds may inhibit the accumulation by AGE of destruction AGE, they can be used as a drug to control and reduce acute bolezn is the R state, such as diabetes and age-related complications caused by the accumulation of AGE.

Increased load AGE in any tissue, probably leads to a pathological condition and different mechanisms can then lead to various diseases. Thus, reducing AGE load tissue, the compounds of the present invention may destroy data state, and prevent the accumulation of AGE up to a critical mass may be preventing the initial occurrence of the disease.

Indeed, in chronic diabetes and in the elderly with age there is a gradual accumulation of AGE (Yong Ming Li et al., 1996 ; Brownlee, 1995). Complications in the event of such mammals occur due to the AGE of the fabric load, increasing with time. The increasing AGE of the fabric load with time can be prevented from newly diagnosed patients through early introduction of compounds that Deplete AGE, or inhibitors of AGE. This method will prevent and/or slow down the development of the above complications in these patients.

AGE inhibitors:

As shown in table 3, the compounds of the present invention can also be used for inhibition of AGE.

Thus, it is possible to use a drug for the treatment of diabetic complications and age-related diseases caused by the accumulation of AGE, because the data connection is to be placed can inhibit the accumulation of AGE by inhibiting the formation of AGE, and they can be used as a drug for the prevention of diseases such as diabetes and age-related complications caused by the accumulation of AGE.

Thus, following a painful condition that occurs due to the formation of AGE, can be prevented or can be treated with compounds of General formula (I) for two reasons: first, because of their AGE destructive activity, and, secondly, because of their AGE-inhibiting activity. Indeed, both kinds of biological activity contribute to the fight against the following diseases:

1) vascular and neurovascular complications

2) renal disease,

3) neurological disease,

4) atherosclerosis

5) disease of the retina

6) dermatological disease

7) the nonenzymatic Browning in the oral cavity,

8) endothelial dysfunction or dysfunction of other organ

9) growth impairment,

10) inflammatory disease

11) immunological violation

12) oxidative stress,

13) the age and diabetic complications,

14) Alzheimer's disease,

15) restenosis, abnormal obstacle tissue in peritoneal dialysis,

16) abnormal obstacle tissue in peritoneal dialysis, and

17) erectile dysfunction.

Example 1D

The activity of removal of free RA is Ikhlov:

This method measures the relative ability of a substance that removes free radicals, to absorb ABTS•+i.e. the radical cation of 2,2-Azino-bis(3-ethylbenzothiazoline-6-sulfonate), compared with standard quantities of standard antioxidants are scavengers of free radicals. Incubation with ABTS peroxidase (metmyoglobin) and hydrogen peroxide leads to the production of the radical cation ABTS•+. This type of radical has a blue-green staining and can be found at 730 nm. Antioxidants or scavengers of free radicals in the added sample cause suppression of color in degree proportional to their concentration.

Protocol:

Receive buffer solutions:

a. Phosphate-citrate buffer (pH 5.0): 48,5 ml 0,1M citric acid with a sufficient quantity of 0,2M dinitrigenoxide with 100 ml.

b. Buffered phosphate saline (PBS): Dissolve 40,0 g NaCl, 1.0 g KCl, 1.0 g KH2PO4and 3.05 g of Na2HPO4in 1 liter of water milli-q Diluted with 200 ml of the above solution up to 1 litre with water milli-Q (pH of 7.4 and 7.6).

Getting ABTS initial solution (2 mm):

1 tablet (10 mg) was dissolved in phosphate-citrate buffer (pH 5.0), getting a 2 mm solution.

Obtain a working solution of horseradish peroxidase:

0.1 mg was dissolved in 10 ml of phosphate buffered physiological RA is down, 1 ml of this solution was diluted to 100 ml using PBS.

Obtaining hydrogen peroxide solution (1,08 mm):

12 μl of hydrogen peroxide (30% wt./about.) was diluted with PBS to 100 ml

To obtain solutions of drugs:

Prepared 0.1 mm initial solutions of medicines which are serially diluted in PBS to obtain solutions with a concentration of 0.05 mm, 0.025 mm and 0.0125 mm.

Obtain the original solution of ABTS radical:

To 2 ml of the original solution of ABTS was added to 1 ml of working solution of horseradish peroxidase.

Since 2 ml of hydrogen peroxide solution was added to the above solution, appeared blue-green ABTS-radicals. This solution is incubated at 30°C for 30 minutes to ensure complete reaction. The volume was brought to 10 ml of PBS.

The reference solution:

900 ál of a solution of ABTS radical was added in a test tube-Eppendorf. To this was added 100 μl of PBS solution.

Obtaining test solution:

900 ál of a solution of ABTS radical was added in different test tubes-Eppendorf. In a test tube was added 100 μl of a solution of a medicinal product in various concentrations.

Measurement of the absorption (OD):

The absorption of the control and test samples was recorded immediately at 730 nm, taking the PBS for the "blank" sample.

Calculation:

About the UNT antioxidant activity was calculated by the formula:

% Antioxidant activity = 100- [OD of test sample/OD of control x 100]

The results are presented below in table 4.

Table 4
Connection # The relative activity of removal of free radicals (%) on ABTS
12.5 μm25,0 µmto 50.0 microns100,0 mcm
Connection 621,9940,5661,6881,04
Compound 822,2238,1867,1499,71
Connection 1041.0172,9785,7587,04
Connection 1126,7845,7470,6186,46
Connection 1222,3440,9771,4784,62
Connection 1323,5841,7864,0182,54
Connection 1728.34 points54,4383,5694,81
The connection 1828,6553,884,4195,32
Connection 19of 8.3719,4237,62/td> 55,18
The connection 206,159,0634,3157,75
The connection 2222,5229,5230,3131,40
Connection 2443,6674.6483,2490,12
The connection 2621,1834,2241,6675,27
Connection 2716,1627,1239,0551,04
The connection 2931,8246,8458,8455,22
The connection 3413,219,0826,3929,40
The connection 35of 28.2739,7858,3474,36
The connection 3721,7937,9241,9539,46
Compound 3827,7044,7861,9866,92

Thus, it was found that compounds of General formula (I), defined above, is capable of removing free radicals, not to mention the fact that they have AGE-inhibitory and AGE-destructive activity.

Discussion of test results on the activity of removal of free radicals:/p>

(i) For cosmetic use

In addition to AGE destroys and removes free radicals activity of the compounds according to the invention, they are able to inhibit AGE, which makes them ideal for a variety of cosmetic applications, as discussed above.

Compounds of the present invention demonstrated the ability of the destruction of AGE cross-links formed in proteins. The compound also demonstrated the ability to remove free radicals, which can cause irreversible damage to proteins, nucleic acids, etc. the Ability to stop the formation of end products increased glycosylation (supports the skin proteins such as collagen, and proteins in the hair, such as keratin, coupled with the ability to remove free radicals is of great consequence and makes them useful in cosmetic applications.

Compounds of the present invention improve the aesthetic of the outer fork of the skin, stopping complications associated with skin, at some crucial stages. They destroy the previously formed end products increased glycosylation (AGE)formed in the supporting skin proteins, and slow intrinsic aging (C. Jeanmaire et. al., British Journal of Dermatology, 2001: 145: 10-18). Compounds of the present invention also removes the free radicals generated during action and ultraviolet light, dirt, etc. in the skin, thus preventing external aging or photoaging. Removal of free radicals will also prevent the irreversible damage caused in proteins and nucleic acids. In addition, by removing free radicals data connections will reduce the load of free radicals generated previously educated AGE. Recovery after oxidative stress, in turn, will reduce the formation of reactive intermediates involved in the formation of the product of Amadori (Amadori).

Glycosylation of proteins is a universal phenomenon, well known at the level of the skin. However, this phenomenon can also occur in other adjacent parts, such as nails or hair, in particular keratin (EP1068864 A1 and EP 1110539 A1).

Glycosylation of skin proteins, in particular collagen, leads to adverse cosmetic effects, such as effects that damage the skin, the same effects can be expected as a result of glycosylation of proteins in the plots close to the skin, such as nails and/or hair, and in the whole protein system.

In the present invention are described molecules with the ability to break down structured proteins. In addition, it is shown that these molecules have the activity of its removal is adnych radicals (antioxidants), and so, in addition to discussed above cosmetic applications, they can be used for a number of diseases, the pathogenesis of which oxidative stress plays a significant role.

Thus, the compounds of the present invention is effective for at least one of the following applications:

a) smooth and prevent wrinkles,

b) smoothing and prevent the formation of facial wrinkles,

c) promotion of growth of the epidermis,

d) the sun protection of the skin,

e) recovery and prevention of discoloration of the skin,

f) recovery and prevention of age spots,

(g) care and prevention of dry skin,

h) recovery and prevention traces of suspenders,

i) recovery and prevention of skin imperfections,

(j) the care of the skin and keep it healthy

k) the recovery and prevention of senile xerosis,

(l) of the skin and prevent sunburn,

m) the prevention and recovery of loss of collagen,

n) improve skin texture,

o) improved skin tone,

p) increasing the thickness of the skin,

q) reduce pore size,

r) restoration of skin luster,

s) minimize signs of fatigue,

t) reduce coal rash,

w) treatment of telangiectasias and

v) improve the aesthetic appearance of the hair and the nail is.

i) For nekommecheskikh applications

In addition to the use of compounds of General formula (I) for cosmetic applications, based on their AGE-destructive/AGE-inhibiting and removing free radicals activity, the activity of these compounds can be used to combat oxidative stress for the effective management of painful conditions.

Listed in the table above compounds have in vitro activity of removal of free radicals (antioxidants). Excessive production of reactive oxidizing species of free radicals (ROS) leading to oxidative stress. Consequently, these molecules would be very effective to reduce oxidative stress through their ability to detect ROS. It is reported that antioxidants (scavengers of free radicals) are effective in controlling various diseases associated with oxidative stress selected from the group including:

1) Neurodegenerative diseases

(a) Alzheimer's Disease

(b) Parkinson's Disease

(c) Huntington's Disease

(d) motor neuron Disease

(e) a prion Disease

2) Diabetes and vascular complications in diabetes

3) Intestinal diseases

(a) Ischemia of the intestine

(b) Radiation enteritis

(c) Inflammatory disease symptoms such the ICA

(d) Cancer of the stomach and colon and rectum

4) liver Disease

(a) Alcoholic liver disease

(b) Chronic hepatitis C

5) Cancer

(a) lung Cancer

(b) Cancer of the colon and rectum

(c) cervical Cancer

(d) breast Cancer

(e) Malignant melanoma

6) heart Disease

(a) Atherosclerosis

(b) myocardial infarction

(c) Ischemic stroke

(d) Endothelial dysfunction

7) Ophthalmic diseases

(a) Formation of cataracts

(b) macular Degeneration

8) HIV disease

9) diseases of the respiratory tract

(a) Chronic obstructive pulmonary disease (COPD)

(b) Asthma

10) kidney Disease

(a) acute glomerulonephritis

(b) Acute renal failure

Obtaining the compounds of the present invention

The following is one possible non-limiting method of producing compounds of the present invention.

Compounds of the present invention can be obtained in accordance with the following stages:

Stage 1: Formation of 1,3-diketonate.

Stage 2: the cyclization Reaction.

Stage 3: the quaternization Reaction.

The following examples give a method of obtaining specific compounds of the invention listed above in table 1.

Stage 1: Formation of 1,3-diketonate

Method 1

1,3-Ticketsairline can b the th obtained by the interaction unsubstituted/substituted acetylpyridine with alkilirovanie esters in a suitable basis

4-(3,5-dimethyl-pyrazole-1-yl)-1-pyridin-3-yl-butane-1,3-dione

To a suspension of tert-butoxide potassium (16.5 g, 0,147 mol) in dry THF, i.e. tetrahydrofuran (150 ml)at 5-10°C in nitrogen atmosphere was added a mixture of 3-acetylpyridine (18 g, 0,148 mole) and ethyl 3,5-dimethylpyrazole, diluted with THF (100 ml). Then the reaction mixture was stirred at room temperature (30° (C) within 6 hours. Then the reaction mixture was poured into ice water and the pH brought up to ˜ to 4.0 with acetic acid and was extragonadal with ethyl acetate (4 × 250 ml). The combined organic layer was washed with a saturated aqueous solution of sodium chloride and finally the organic layer was washed with water and dried over sodium sulfate. The ethyl acetate was concentrated in vacuum at 50°C, receiving the crude product. Subsequent rubbing with a spatula in diethyl ether gave a solid product. The separated solid was filtered and dried, obtaining the target product.

Output: 12,0,

1H NMR (DMSO-d6, 400 MHz) δ: of 8.95 (1H, s), 8,75-8,73 (1H, d), 8,11-8,08 (1H, m), 7,42-7,39 ( 1H, m), 5,95 ( 1H, s ), 5,78 (1H, s), 4,89 (2H, s), of 2.28 (3H, s), are 2.19 (3H, s).

Mass spectrum (m/z): 258, 259.

IR (KBr cm-1): 2924, 1621, 1557, 1455.

Method 2

Alternatively, 1,3-ticketsairline can be obtained by the interaction unsubstituted/substituted arolovich esters with unsubstituted/substituted arylmethylidene in a suitable the base.

Obtain 1-phenyl-3-quinoline-3-yl-propane-1,3-dione

A solution of ethyl-3-girolata (0.50 g, 0,0025 mol) and acetophenone (0,30 g 0,0025 mole) doublely to a cooled ice suspension of tert-butoxide potassium in THF (5.0 ml). The reaction mixture was stirred at room temperature for 2 hours, acidified with diluted acetic acid (10%). The obtained solid was filtered, dried in air, and recrystallized from boiling ethyl acetate, obtaining the desired product in the form of painted pale yellow solid.

Output: 0,20,

1H NMR (DMSO-d6, 400 MHz) δ: 9,58 (1H, s), 9,23 (1H, s), 8,25-8,13 (4H, m), 7,94 (1H, t), to 7.77 to 7.62 (5H, m).

Mass spectrum (m/z): 272.

Stage 2: the cyclization Reaction

3-[3-{(3,5-Dimethylpyrazol-1-ylmethyl)-1-phenyl}pyrazole-5-yl]pyridine

To a stirred cooled solution of 4-(3,5-dimethylpyrazol-1-yl)-l-pyridin-3-yl-butane-1,3-dione (0.8 g, of 0.003 mol) in methanol (30 ml) was slowly added phenyl hydrazine (0.6 g, of 0.005 mol) in methanol (10 ml). The reaction mixture was stirred at room temperature (30° (C) within 3 hours and are condensed under reduced pressure, obtaining the crude oily product. The crude product was purified on a column of silica gel using a mixture of ethyl acetate:hexane (1:1) as eluent, obtaining the desired product as a yellow solid.

Output: 0,6,

1H NMR (DMSO-d 6, 400 MHz) δ: charged 8.52-and 8.50 (1H, d), 8,42 (1H, s), to 7.59-7,56 (1H, m), 7,45-7,34 (4H, m), 7,28-7,26 (2H, m), to 6.57 (1H, s), of 5.83 (1H, s), 5,23 (2H, s), 2,31 (3H, s), is 2.09 (3H, s).

Mass spectrum (m/z): 330, 331, 332.

3-[3-(3,5-Dimethyl-pyrazole-1-yl-methyl)pyrazole-5-yl]pyridine

To a stirred cooled solution of 4-(3,5-dimethylpyrazol-1-yl)-1-pyridin-3-ivatan-1,3-dione (2.5 g, 0,0097 mol) in methanol (70 ml) was slowly added hydrazinehydrate (3,0 ml of 0.06 mol). The reaction mixture was stirred at room temperature (30°C) for 3 hours and concentrated under reduced pressure, obtaining an oily substance. Added chilled water and the reaction mixture was rubbed out with a spatula, getting solid. The separated solid was filtered and recrystallized from methanol, obtaining the target product.

Output: 1, 35g.

1H NMR (DMSO-d6, 400 MHz) δ: 8,98-of 8.95 (1H, d), 8,50-8,48 (1H, d), 8,11 (1H, s), 7,45-7,40 (1H, d), 6,66-of 6.61 (1H, d), of 5.81 (1H, s), to 5.21-5,14 (2H, d), of 2.28 (3H, s)2,07 (3H, s).

Mass spectrum (m/z): 254, 255.

3-[3-{(3,5-Dimethyl-pyrazole-1-ylmethyl)-1-cyclohexyl}pyrazole-5-yl]pyridine

To the cooled solution triperoxonane acid (22,2 g of 0.20 mole) was added 1-(tert-butoxycarbonyl)cyclohexylpiperazine (5.0 g, 0,0236 mol) and stirred at room temperature (30° (C) within 30 minutes. The reaction mixture was concentrated under reduced pressure, obtaining the crude oily product. To the crude product which I had added water (10 ml) and neutralized with saturated sodium bicarbonate solution. The neutralized solution was extracted with ethyl acetate (3×75 ml). The combined organic layer was dried over sodium sulfate and concentrated in vacuum, obtaining the crude oily product (2.50 g).

Next, the oily product (2.50 g, of 0.022 mole)dissolved in methanol (10 ml), was slowly added to a solution of 4-(3,5-dimethyl-pyrazole-1-yl)-1-pyridin-3-yl-butane-1,3-dione (2.0 g, 0,0078 mol) in methanol (20 ml). The reaction mixture was stirred at room temperature (30°C) for 7 hours, then concentrated under reduced pressure, obtaining the oily product is brown. Purification of the crude product was performed column chromatography on silica gel using 25% ethyl acetate in hexane as the eluent, obtaining the desired product as a white solid.

Output: 0,96 g

1H NMR (DMSO-d6, 400 MHz) δ: 8,65-8,63 (1H, m), a 7.85-of 7.82 (1H, m), 7,54-7,51 (1H, m), x 6.15 (1H, s), 5,8 (IH, s)to 5.13 (2H, s), 3,98 (1H, m), and 2.27 (3H, s)2,07 (3H, s), 1,91-of 1.85 (4H, m), of 1.78 and 1.75 (2H, m), 1,62-1,559, (1H, m), 1,27-of 1.16 (3H, m).

Mass spectrum (m/z): 336, 337, 338.

Synthesis of 3-[3-(phenylmethyl)isoxazol-5-yl]pyridine.

A mixture of phenyldimethylsilane 0,500 g (0,0021 mol), isopropyl alcohol (IPA) (5 ml) and hydroxylamine in the form of the free base (7 ml methanol) was stirred at room temperature for 3 days (72 hours). The reaction mixture was concentrated to dryness and purified colonic the second chromatography using a mixture of ethyl acetate and hexane (3:1). The purified compound (oxime) was dissolved in IPA (10 ml) was added 2 N. HCl (4 drops). The reaction mixture was heated at the boil under reflux for 8 hours. Finally, the reaction mixture was concentrated to dryness, obtaining the target compound as a pale yellow solid.

Output: 0,216,

1H NMR (DMSO-d6, 400 MHz) δ: 9,01 (1H, s), 8,69 (1H, d), to 8.20 (1H, d), 7,56 (m, 1H), was 7.36-7,30 (m, 5H), 6,46 (1H, s), 4,11 (2H, s).

Mass spectrum (m/z): 237 (M++1).

Stage 3: the quaternization Reaction

The quaternization of the substituted pyridine can be performed using reagent quaternization of alcohol and/or high-boiling solvent at boiling under reflux for onset 6 to 48 hours with obtaining, if necessary, the target of the connection.

Example 2.

Bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[3-{1-(3,5-dimethylpyrazol-1-yl)methyl}pyrazole-5-yl]pyridinium (Compound 4).

To a suspension of 3-[3-(3,5-dimethylpyrazol-1-yl-methyl)pyrazole-5-yl]pyridine (0.5 g, of 0.002 mol) in IPA (35 ml) was added α-bromo-2-acetylthiophene (0,46 g, 0,0026 mol). The reaction mixture was heated at boiling under reflux for 6 hours. Then cooled the mixture to room temperature (30°C). The separated solid was filtered and precrystallization using a mixture of methanol and ethyl acetate, obtaining the desired compound as a white solid.

Output: 0,51,

1H NMR (DMSO-d6, 400 MHz) δ: 13,66 (1H, s), 9,49 (1H, s), 9,03-9,01 (1H, d), 8,89-8,88 (1H, d), compared to 8.26-8,21 (3H, m), 7,43-7,41 (1H, t), 6,77 (1H, s), to 6.39 (2H, s), of 5.84 (1H, s)at 5.27 (2H, s), and 2.27 (3H, s), of 2.08 (3H, s).

Mass spectrum (m/z): 378, 379, 380.

IR (KBr, cm-1): 1676, 1638, 1591.

Compounds of the invention identified by physico-chemical data given below in the examples 3-57, were obtained in accordance with the above method of synthesis.

Example 3.

Bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium (Connection 1).

Yield: 51 %.

IR (KBr, cm-1): 1656, 1637, 1572.

1H NMR (DMSO-d6, 400 MHz) δ: 13,44 (1H, s), 9,46 (1H, s), 8,98 (1H, d), 8,86 (1H, d), 8,24 (3H, m), 7,41 (1H, t), 7,34-7,30 (5H, m), 6,69 (1H, s)6,38 (2H, s)4,06 (2H, s).

Mass spectrum (m/z): 360, 361, 362, 363.

Example 4.

Bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(5-phenylmethyl)oxazol-3-yl]pyridinium (Compound 2).

Yield: 36%.

IR (KBr, cm-1): 1747, 1671, 1456.

1H NMR (DMSO-d6, 400 MHz) δ: 9,65 (1H, s), 9,12-remaining 9.08 (2H, m) 8,39 (1H, t) compared to 8.26-8,23 (2H, m), 7,42 (1H, m), 7,38-7,33 (5H, m), 7.23 percent (1H, s) 6,40 (2H, s), is 4.15 (2H, s).

Mass spectrum (m/z): 361, 362, 363.

Example 5.

Dibromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[3-{1-(2-Tien-2'-yl)-2-oxoethylidene-4-thio}methylpyrazole-5-yl]pyridinium. (Compound 3).

Yield: 71%.

IR (KBr, cm-1): 1666, 1500, 1451.

1H NMR (DMSO-d6, 400 MHz) δ: 13,81 (1H, s), 9,54 (1H, s), 9,03-9,01 (1H, d), 8,93-8,91 (1H, d), 8,71-8,69 (2H, d), 8.30 to-8,13 (7H, m), 7,44-7,39 (2H, m), to 7.09 (1H, s), 42 (2H, C), 6,21 (2H, s), 4,84 (2H, s).

Mass spectrum (m/z): 517, 518, 519, 520.

Example 6.

Bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[{3-phenylmethyl}-1-{2-pyridyl}pyrazole-5-yl]pyridinium (Compound 5).

Yield: 22%.

IR (KBr, cm-1): 1671, 1585, 1550.

1H NMR (DMSO-d6, 400 MHz) δ: 9,24 (1H, s), 8,96-of 8.95 (1H, d), 8,24-8,21 (2H, m), 8,19-8,18 (1H, d), 8,15-to 8.14 (1H, d), 8.07-a 8,02 (1H, m), 7,97-of 7.95 (1H, d), 7,41-7,31 (6H, m), 7,25-7,22 (1H, m), 6,76 (1H, s), 6,32 (2H, ), 4,08 (2H, s).

Mass spectrum (m/z): 437, 438, 440.

Example 7.

Bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[3{(3,5-dimethylpyrazol-1-yl)methyl-1-(2-pyridyl)}pyrazole-5-yl]pyridinium (Compound 6).

Yield: 31%.

IR (KBr, cm-1): 3418, 3069, 2929, 1670, 1507, 1470.

1H NMR (DMSO-d6, 400 MHz) δ: a 9.25 (1H, s), 8,97-of 8.95 (1H, d), 8,61-8,59 (1H, d), 8,24-8,16 (4H, m), 8,09-with 8.05 (1H, m), 7,94-a 7.92 (1H, d), 7,42-7,39 (2H, m), 6,72 (1H, s), 6,33 (2H, s), to 5.85 (1H, s), 5,31 (2H, s), 2,33 (3H, s), of 2.08 (3H, s).

Mass spectrum (m/z): 455, 456, 457, 458.

Example 8.

Bromide 1-[2-(cyclopropylamino)-2-oxoethyl]-3-[3-(3,5-dimethylpyrazol-1-yl)methyl}pyrazole-5-yl]pyridinium (Compound 7).

Yield: 59%.

IR (KBr, cm-1): 3373, 3064, 1667, 1577.

1H NMR (DMSO-d6, 400 MHz) δ: 13,69 (1H, s), 9,41 (1H, s), of 8.95 (1H, d), 8,55 (1H, d), 8,54 (1H, d), 8,16 (1H, t), to 6.80 (1H, s), of 5.84 (1H, s), of 5.39 (2H, s), of 5.26 (2H, s), 3,89-3,82 (1H, m), and 2.27 (3H, s), of 2.08 (3H, ), 1,12 (4H, d).

Mass spectrum (m/z): 353, 354, 355.

Example 9.

Bromide 1-{2-(4-nitro-2-thienyl)-2-oxoethyl}-3-[3-{(3,5-dimethylpyrazol-1-yl)methyl}pyrazole-5-yl]pyridinium (Compound 8).

Yield: 24%.

IR (KBr, cm-1):

1 H NMR (DMSO-d6, 400 MHz) δ: 13,70 (1H, s), for 9.47 (1H, s), of 9.30 (1H, s), 9,03 (1H, d), 8,87 cent to 8.85 (2H, m), compared to 8.26 (1H, t), 6,77 (1H, s), 6.42 per (2H, s), of 5.84 (1H, s)at 5.27 (2H, s), and 2.27 (3H, s)2,07 (3H, s).

Mass spectrum (m/z): 423, 424.

Example 10.

Chloride 1-(2-cyclopropylamino-2-oxoethyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium (Compound 9).

Yield: 36%.

IR (KBr, cm-1): 3653, 3436, 3061, 1674, 1567, 1479.

1H NMR (DMSO-d6, 400 MHz) δ: 13,46 (1H, s), 9,37 (1H, s), 8,93 (1H, d), 8,82 (1H, d), 8,72-8,71 (1H, d), 8,19-to 8.14 (1H, t), of 7.36-7.23 percent (5H, m), 6,72 (1H, s)5,38 (2H, s)4,06 (2H, s), 2.71 to to 2.66 (1H, m), 0.70 to 0,66 (2H, m)at 0.50 and 0.46 (2H, m).

Mass spectrum (m/z): 333, 334, 335.

Example 11.

Dibromide 3,5-bis-[1-(2-Tien-2'-yl-2-oxoethyl)pyridine-3-yl]pyrazole (Compound 10).

Yield: 34%.

IR (KBr, cm-1): 3425, 3088, 2927, 1673, 1505, 1407.

1H NMR (DMSO-d6, 400 MHz) δ: a 9.09-9,02 (4H, m), to 8.41 (2H, users), 8,27 compared to 8.26 (4H, m), 7,66 (1H, s), 7,45-the 7.43 (2H, t), 6,47 (4H, s).

Mass spectrum (m/z): 471, 472, 473, 474.

Example 12.

Chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(l-phenyl-3-phenylmethyl)pyrazole-5-yl]pyridinium (Compound 11).

Yield: 42%.

IR (KBr, cm-1): 3302, 3029, 1672, 1503.

1H NMR (DMSO-d6, 400 MHz) δ: 9,20 (1H, s), 8,94-8,93 (1H, d), 8,24-to 8.20 (3H, m), 8,16-8,13 (1H, m), 7,50-7,31 (10H, m), 7,25-of 7.23 (1H, m), of 6.73 (1H, s), 6,32 (2H, s)4,06 (2H, s).

Mass spectrum (m/z): 436, 437, 438, 439, 440.

Example 13.

Chloride 1-(2-(5-methyl-2-thienyl)-2-oxoethyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium (Compound 12).

Yield: 44%.

IR (KBr, cm-1): 3745, 1654, 1518, 1455.

1H NMR (DMSO-d , 400 MHz) δ: 13,52 (1H, s), 9,48 (1H, s), 8,99-8,97 (1H, d), 8,90-8,88 (1H, d), 8,24-8,21 (1H, t), 8,04-8,03 (1H, d), 7,35-7,22 (5H, m), 7,14-7,13 (1H, d), 6,70 (1H, s), 6,36 (2H, s)4,07 (2H, s), 2,59 (3H, s).

Mass spectrum (m/z): 374, 375, 376, 377.

Example 14.

Chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[1-phenyl-3-{(3,5-dimethylpyrazol-1-yl)methyl)}pyrazole-5-yl]pyridinium (Compound 13).

Yield: 27%.

IR (KBr, cm-1):

1H NMR (DMSO-d6, 400 MHz) δ: which 9.22 (1H, s), 8,95-8,93 (1H, d), 8,25-8,21 (3H, m), 8,16-to 8.12 (1H, m), of 7.64-of 7.60 (1H, m), 7,50-7,46 (2H, m), 7,42 and 7.36 (3H, m), of 6.71 (1H, s), 6,33 (2H, s), of 5.84 (1H, s), 5,28 (2H, s), 2,29 (3H, s), of 2.08 (3H, s).

Mass spectrum (m/z): 454, 455, 456, 457, 458.

Example 15.

Bromide 1-(2-phenyl-2-oxoethyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium (Compound 14).

Yield: 14%.

IR (KBr, cm-1): 3746, 3099, 1691, 1518.

1H NMR (DMSO-d6, 400 MHz) δ: 13,44 (1H, s), to 9.45 (1H, s), 9,01-8,99 (1H, d), cent to 8.85-8,84 (1H, d), compared to 8.26-8,23 (1H, t), 8.07-a of 8.06 (2H, d), 7,82 for 7.78 (1H, t), 7,69-the 7.65 (2H, t), of 7.36-7,21(5H, m), of 6.68 (1H, s), 6,45 (2H, s), 4,07 (2H, s).

Mass spectrum (m/z): 354, 355.

Example 16.

Chloride 1-(2-cyclopropylamino-2-oxoethyl)-3-[(1-phenyl-3-phenylmethyl)pyrazole-5-yl]pyridinium (Compound 15).

Output: 7%.

IR (KBr, cm-1): 3395, 3026, 1689, 1503.

1H NMR (DMSO-d6, 400 MHz) δ: 9,15 (1H, s), 8,86 (1H, s)8,71 (1H, s), 8,14-with 8.05 (2H, m), 7,44-of 7.23 (10H, m), 6,74 (1H, s), 5,31 (2H, s), of 4.05 (2H, s), 2,66 (1H, s), 0,68 is 0.67 (2H, s), and 0.46 (2H, s).

Mass spectrum (m/z): 409, 410, 411, 412.

Example 17.

Bromide 1-(2-(4-benzyl-1-piperidinyl)-2-oxoethyl)-3-[(3-phenoxymethyl)pyrazole-5-yl]pyridinium (Compound 16).

Output:

IR (KBr, cm-1): 3060, 1656, 1594.

1H NMR (DMSO-d6, 400 MHz) δ: at 13.84 (1H, s), to 9.45 (1H, s), 8,98 (1H, d), 8,83 (1H, d), 8,21 (1H, t), 7,35-7,27 (4H, m), 7.23 percent-7,19 (3H, m), 7,09? 7.04 baby mortality (3H, m), 6,98 (1H, t), of 5.83-5,73 (2H, m), a total of 5.21 (2H, s), the 4.29 (1H, d), of 3.75 (1H, d), 3,17-3,0 (1H, m), 2,69-2,63 (1H, m), of 2.56 (2H, d), 1,99-of 1.84 (1H, m), 1,72 is 1.60 (2H, m), 1,36 of 1.28 (1H, m), 1,10-1,04 (1H, m).

Mass spectrum (m/z): 467, 468, 469.

Example 18.

Chloride 1-(2-phenyl-2-oxoethyl)-3-[(3-(3,5-dimethylpyrazol-1-yl)methyl)pyrazole-5-yl]pyridinium (Compound 17).

Yield: 24%.

IR (KBr, cm-1); 3049, 2994, 1692, 1552.

1H NMR (DMSO-d6, 400 MHz) δ: 13,76 (1H, s), 9,50 (1H, s), 9,03-of 9.02 (1H, d), 8,90-8,88 (1H, d), compared to 8.26 (1H, users), 8,08-of 8.06 (2H, d), 7,81 for 7.78 (1H, m), 7.68 per-the 7.65 (2H, m), of 6.75 (1H, s), of 6.49 (2H, s), of 5.83 (1H, s), of 5.26 (2H, C), and 2.26 (3H, s)to 2.06 (3H, s).

Mass spectrum (m/z): 372, 373, 374.

Example 19.

Chloride 1-(2-(5-methyl-2-thienyl)-2-oxoethyl)-3-[(3-(3,5-dimethylpyrazol-1-yl)methyl)pyrazole-5-yl]pyridinium (Compound 18).

Yield: 34%.

IR (KBr, cm-1): 3322, 2923, 1659, 1552.

1H NMR (DMSO-d6, 400 MHz) δ: 13,71 (1H, s), 9,48 (1H, s), 9,01-8,99 (1H, d), 8,89-8,87 (1H, d), 8,23 (1H, users), 8,04-8,03 (1H, d), 7,13 (1H, s)6,76 (1H, s), 6,33 (2H, s), of 5.83 (1H, s), of 5.26 (2H, s), 2,58 (3H, s), 2.26 and (3H, s)2,07 (3H, s).

Mass spectrum (m/z): 392, 393, 394, 395.

Example 20.

Chloride 1-(2-phenyl-2-oxoethyl)-3-[(1-phenyl-3-phenylmethyl)pyrazole-5-yl]pyridinium (Compound 19).

Yield: 63%.

IR (KBr, cm-1): 3351, 3235, 3030, 1694, 1504.

1H NMR (DMSO-d6, 400 MHz) δ: 9,17 (1H, s), 8,93-8,91 (1H, d), 8,25-8,23 (1H, d), 8.17-a to 8.14 (1H, t), 8,06-of 8.04 (2H, d), 7,81 for 7.78 (1H, t, 7,68-to 7.64 (2H, t), 7,49-7,44 (3H, m), 7,38-7,30 (6H, m), 7.24 to 7,20 (1H, m), 6,72 (1H, s)6,40 (2H, s), of 4.05 (2H, s).

Mass spectrum (m/z): 430, 431, 432.

Example 21.

Chloride 1-(2-(5-methyl-2-thienyl)-2-oxoethyl)-3-[(3-(2-cyclohexylethyl)pyrazole-5-yl]pyridinium (Compound 20).

Yield: 30%.

IR (KBr, cm-1): 3072, 2920, 1658, 1519, 1450.

1H NMR (DMSO-d6, 400 MHz) δ: 13,33 (1H, s)9,52 (1H, s), 8,99-8,97 (1H, d), 8,92-of 8.90 (1H, d), compared to 8.26 is 8.22 (1H, t), 8,06-with 8.05 (1H, d), 7,14 (1H, s)6,76 (1H, s)6,40 (2H, s), 2.71 to to 2.67 (2H, t), at 2.59 (3H, s), 1,75-1,63 (5H, m), 1,57-of 1.52 (2H, HF), 1,24-of 1.16 (4H, m), 0,95-of 0.90 (2H, m).

Mass spectrum (m/z): 394, 395, 396.

Example 22.

Chloride 1-(2-cyclopropylamino-2-oxoethyl)-3-[(3-(2-cyclohexylethyl)pyrazole-5-yl]pyridinium (Compound 21).

Yield: 39%.

IR (KBr, cm-1): 3174, 2923, 1682, 1548.

1H NMR (DMSO-d6, 400 MHz) δ: 13,25 (1H, s), 9,40 (1H, s), 8,94-8,91 (1H, d), cent to 8.85-8,84 (1H, d), 8,60-8,58 (1H, d), 8,18-of 8.15 (1H, m), 6,79 (1H, s), 5,43 (2H, s), 3,90-of 3.85 (1H, m), 2.71 to to 2.67 (2H, t), a 1.75-to 1.63 (5H, m), 1,58-of 1.52 (2H, HF), 1,24-1,12 (8H, m), 0,96-0,88 (2H, m).

Mass spectrum (m/z): 355, 356, 357.

Example 23.

Chloride 1-(2-phenyl-2-oxoethyl)-3-[(3-(2-cyclohexylethyl)pyrazole-5-yl]pyridinium (Compound 22).

Yield: 65%.

IR (KBr, cm-1): 3059, 2924, 1698, 1519.

1H NMR (DMSO-d6, 400 MHz) δ: 13,26 (1H, s), 9,49 (1H, s), 9,00-8,98 (1H, d), 8,88-8,86 (1H, d), 8,28-8,24 (1H, m), 8,09-8,07 (2H, d), 7,83-7,79 (1H, t), 7,70-7,66 (2H, t), of 6.75 (1H, s), 6,50 (2H, s), 2,69 (2H, t), a 1.75-to 1.61 (5H, m), 1,58-of 1.52 (2H, HF), 1,27-1,08 (4H, m), 0,96-0,88 (2H, m).

Mass spectrum (m/z): 374, 375, 376.

Example 24

Chloride 1-(2-cyclopropylamino-2-oxoethyl)-3-[(1-cyclohe the power-3-phenylmethyl)pyrazole-5-yl]pyridinium (Compound 23).

Yield: 9%.

IR (KBr, cm-1): 3165, 2994, 1662, 1500, 1452.

1H NMR (DMSO-d6, 400 MHz) δ: 9,11 (1H, s), 9,01-9,00 (1H, d), 8,69-8,67 (1H, d), 8,60-8,58 (1H, d), 8,27-8,24 (1H, m), 7,33-7,29 (4H, m), 7,22-7,19 (1H, m), 6,38(1H,s), 5,42 (2H, s), 4,08-was 4.02 (1H, m), of 3.96 (2H, s), 3,91-of 3.85 (1H, m), 1,89 (4H, users), of 1.78 and 1.75 (2H, d), 1,64-to 1.61 (1H, d), of 1.41 (2H, users), 1,21-of 1.16 (1H, m), 1,13-1,12 (4H, d).

Mass spectrum (m/z): 417, 418, 419.

Example 25

Chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(3-phenoxymethyl)pyrazole-5-yl]pyridinium (Compound 24).

Yield: 18%.

IR (KBr, cm-1): 3060, 2957, 1665, 1595, 1491.

1H NMR (DMSO-d6, 400 MHz) δ: 13,82 (1H, s), 9, 55 (1H, s), 9,06-9,04 (1H, d), 8,93-8,91 (1H, d), 8,30 is 8.22 (3H, m), 7,44-the 7.43 (1H, m), 7,35-7,31 (2H, m), 7,08-7,05 (3H, m), 7,01-6,97 (1H, m), to 6.43 (2H, s), with 5.22 (2H, ).

Mass spectrum (m/z): 376, 377, 378.

Example 26

Chloride 1-{2-(1-adamantylamine-2-oxoethyl)}-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium (Compound 25).

Yield: 27%.

IR (KBr, cm-1): 3060, 2908, 1679, 1554.

1H NMR (DMSO-d6, 400 MHz) δ: 13,45 (1H, s), a 9.35 (1H, s), 8,91 (1H, d), 8,80 (1H, d), to 8.20 (1H, s)to 8.14 (1H, t), 7,35-7,31 (5H, m), 6,74 (1H, s), are 5.36 (2H, s), 4, 07 (2H, s), 2,02-1,95 (9H, m), 1, 62 (6H, s).

Mass spectrum (m/z): 427, 428, 429.

Example 27

Bromide 1-(2-phenyl-2-oxoethyl)-3-[{3-(3,5-dimethylpyrazol-1-yl)methyl)}-1 phenylpyrazol-5-yl]pyridinium (Compound 26).

Yield: 47%.

IR (KBr, cm-1): 3410, 3035, 2943, 1693, 1500.

1H NMR (DMSO-d6, 400 MHz) δ: 9,19 (1H, s), 8,93-8,91 (1H, d), 8,25-8,23 (1H, d), 8,18-to 8.14 (1H, m), 8.07-a with 8.05 (2H, m), 7,82-7,79 (1H, m), 7,69-to 7.64 (2H, m), 7,53-7,47 (3H, m), 7,40-7,37 (2H, m), of 6.71 (1H, s)6,40 (2H, the), of 5.84-of 5.83 (1H, s), 5,28 (2H, s)to 2.29 (3H, s), of 2.08 (3H, s).

Mass spectrum (m/z): 448, 449.

Example 28

Bromide 1-(2-(4-nitro-2-thienyl)-2-oxoethyl)-3-[(1-cyclohexyl-3-(3,5-dimethylpyrazol-1-yl)methyl)pyrazole-5-yl]pyridinium (Compound 27).

Yield: 56%.

IR (KBr, cm-1): 3421, 3032, 2935, 1688, 1541.

1H NMR (DMSO-d6, 400 MHz) δ: of 9.30 (1H, d), with 9.14 (1H, s), 9,04-of 9.02 (1H, d), 8,87-8,86 (1H, d), 8,79-8,77 (1H, d), scored 8.38-8,35 (1H, m), 6,46 (2H, s), 6,36 (1H, s), of 5.82 (1H, s), is 5.18 (2H, s), 4,15-4,10 (1H, m), of 2.25 (3H, C)2,07 (3H, s), 1,90-of 1.84 (4H, m), 1,81-to 1.77 (2H, d), 1,66-1,63 (1H, d), 1,38-1,19 (3H, m).

Mass spectrum (m/z): 505, 506, 507.

Example 29

Bromide 1-(2-(4-nitro-2-thienyl)-2-oxoethyl)-3 [(3-(2-cyclohexylethyl)pyrazole-5-yl]pyridinium (Compound 28).

Yield: 48%.

IR (KBr, cm-1): 3078, 3005, 1695, 1541, 1339.

1H NMR (DMSO-d6, 400 MHz) δ: 13,24 (1H, s), 9,48 (1H, s), of 9.30 (1H, s), and 9.0 (1H, d), 8,87-8,84 (2H, m), of 8.27 (1H, t)6,76 (1H, s), 6,46 (2H, s), 2,69 (2H, t), 1,99-to 1.61 (5H, m), 1,58-of 1.52 (2H, HF), 1,26-1,12 (4H, m), 0,96-of 0.87 (2H, m).

Mass spectrum (m/z): 425.

Example 30

Chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(1-phenyl-3-phenoxymethyl)pyrazole-5-yl]pyridinium (Compound 29).

Yield: 16%.

IR (KBr, cm-1): 3347, 3022, 2906, 1682, 1503.

1H NMR (DMSO-d6, 400 MHz) δ: 9,3 (1H, s), and 9.0 (1H, s), 8,29-8,24 (4H, m), of 7.6 to 7.3 (8H, m), 7,0 (3H, s), 6,97 (1H, s)6,38 (2H, s), and 5.2 (2H, s).

Mass spectrum (m/z): 452, 453, 454.

Example 31

Bromide 1-(2-(4-nitro-2-thienyl)-2-oxoethyl)-3-[(1-phenyl-3-phenylmethyl)pyrazole-5-yl]pyridinium (Compound 30).

Yield: 23%.

IR (KBr, cm-1): 3092, 3003, 2932, 1687, 1509.

1H NMR (DMSO-d6, 400 MHz) δ: 9,298 (1H, s), 9,16 (1H, s)8,917 (1H, d), cent to 8.85-8,84 (1H, m), 8,54 (1H, d), 8.17-a to 8.14 (1H, m), 7,50 was 7.45 (3H, m), 7,39-7,31 (6H, m), 7,25-7,22 (1H, m), 6,7 (IH, s)6,357 (2H, s), 4,0 (2H, C).

Mass spectrum (m/z): 481, 482.

Example 32

Chloride 1-(2-cyclopropylamino-2-oxoethyl)-3-[(3-phenoxymethyl)pyrazole-5-yl]pyridinium (Compound 31).

Yield: 34%.

IR (KBr, cm-1): 3647, 3420, 3227, 2958, 1675.

1H NMR (DMSO-d6, 400 MHz) δ: 13,82 (1H, s), 9,46 (1H, s), 8,98 (1H, s), 8,87 (1H, d), 8,77 (1H, m), (1H, d), 8,207 (1H, t), 7,33 (2H, t), and 7.1 (1H, s)7,059 (2H, d), 6,98 (1H, t), 5,4 (2H, s), a total of 5.21 (2H, s), 2,7-of 2.68 (1H, m), 0,715-0,685 (2H, m), 0.55 to 0.50 in (2H, m).

Mass spectrum (m/z): 349, 350, 351.

Example 33

Chloride 1-(2-cyclopropylamino-2-oxoethyl)-3-[(1-cyclohexyl-3-(3,5-dimethylpyrazol-1-yl)methyl)pyrazole-5-yl]pyridinium (Compound 32).

Yield: 41%.

IR (KBr, cm-1): 3425, 3174, 2938, 1658, 1500.

1H NMR (DMSO-d6, 400 MHz) δ: 9,1 (1H, s), of 9.02 (1H, d), 8,88 (1H, d), 8,86 (1H, d), 8,273 (1H, t), 6,36-6,34(1H,s), and 5.8 (1H,s), 5,4 (2H,s), is 5.18 (2H, s), 4,13-4,079 (1H, m), 2,7-of 2.68 (1H, m), and 2.26 (3H, s), 2,074 (3H, s), 1,99 is 1.75 (6H, m), 1,64-to 1.61 (1H, m), 1,34 to 1.31 (2H, m), 1,24-1,17 (1H, m), 0.70 to 0,69 (2H, m), 0.50 to 0,49 (2H, m).

Mass spectrum (m/z): 433, 434, 435.

Example 34

Bromide 1-(2-(5-chloro-2-thienyl)-2-oxoethyl)-3-[(3-phenoxymethyl)pyrazole-5-yl]pyridinium (Compound 33).

Yield: 74%.

IR (KBr, cm-1): 2853, 2682, 1674, 1594.

1H NMR (DMSO-d6, 400 MHz) δ: 13,8 (1H, s), at 9.53 (1H, s), 9,03 (1H, d), 8,89 (1H, d), 8,3 compared to 8.26 (1H, m), 8,16(1H, d), and 7.5 (1H, d), 7,33 (2H, t), was 7.08 (3H, t), 6,98 (1H, t), 6,38 (2H, s), and 5.2 (2H, s).

Mass spectrum (m/z: 410, 412, 413.

Example 35

Chloride 1-(2-phenyl-2-oxoethyl)-3-[(1-phenyl-3-phenoxymethyl)pyrazole-5-yl]pyridinium (Compound 34).

Yield: 25%.

IR (KBr, cm-1): 3020, 2905, 1701, 1634, 1595.

1H NMR (DMSO-d6, 400 MHz) δ: 9,23 (1H, s), 8,96 (1H, d), with 8.33 (1H, d), 8,21 (1H, t), 8,07 (2H, d), 7,81 (1H, t), 7,68 (2H, t), 7,51 is 7.50 (3H, m), 7, 41 (2H, d), 7,32 (2H, t), 7,08-7,06 (3H, m), 6,97 (1H, t), 6.42 per (2H, s), a total of 5.21 (2H, s).

Mass spectrum (m/z): 446, 447.

Example 36

Chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(1-cyclohexyl-3-(3,5-dimethylpyrazol-1-yl) methyl)pyrazole-5-yl]pyridinium (Compound 35).

Yield: 26%.

IR (KBr, cm-1): 3422, 2937, 1678, 1505, 1251.

1H NMR (DMSO-d6, 400 MHz) δ: 9,17 (1H, s), 9,05 (1H, d), 8,76 (1H, d), 8,35 (1H, t), 8,25-8,24 (2H, m), 7,42 (1H, t), 6,41 (2H, s), 6,36 (1H, s), to 5.85 (1H, s), is 5.18 (2H, s), 4,13-4,10 (1H, m), of 2.25 (3H, s)to 2.06 (3H with), 1,99 is 1.86 (4H, m), 1,83 to 1.76 (2H, m), 1,66-to 1.63 (1H, m), 1,35-1,25 (2H, m), 1,22-of 1.16 (1H, m).

Mass spectrum (m/z): 460, 461, 462.

Example 37

Bromide 1-(2-cyclopropylamino-2-oxoethyl)-3-[(1-phenyl-3-phenoxymethyl)pyrazole-5-yl]pyridinium (Compound 36).

Yield: 9%.

IR (KBr, cm-1): 3200, 1682, 1595.

1H NMR (DMSO-d6, 400 MHz) δ: 9,29 (1H, s), 9,06 (1H, s), 8,97 (1H, d), 8,21 (1H, d), 8,10 (1H, t), of 7.48 (3H, s), 7,39-to 7.18 (5H, m), 7,14-7,07 (2H, m), 6,97 (1H, t), 5,43 (2H, s), 5,20 (2H, s), 2,68-2,62 (1H, m), 0.70 to for 0.62 (2H, m), and 0.50 to 0.44 (2H, m).

Mass spectrum (m/z): 425, 426, 427.

Example 38

Bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(1-phenyl-3-(2-cyclohexylethyl)pyrazole-5-yl]pyridinium (Compound 37).

Yield: 31%.

IR (KBr, cm-1): 3423, 3324, 2922, 1674, 1506.

1H NMR (DMSO-d6, 400 MHz) δ: a 9.25 (1H, s), 8, 90 (1H, d), 8,27-8,23 (3H, m), 8,19-of 8.15 (1H, m), 7,49-7,41 (4H, m), 7,35 (2H, d), 6,8 (1H, s), 6,37 (2H, s), 2,69 (2H, t), is 1.77 (2H, d), 1,69-of 1.55 (5H, m), 1,32 (1H, m), 1,26-of 1.12 (3H, m), 0,97-0,89 (2H, m).

Mass spectrum (m/z): 456, 457, 458.

Example 39

Chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(1-cyclohexyl-3-phenoxymethyl)pyrazole-5-yl]pyridinium (Compound 38).

Yield: 18%.

IR (KBr, cm-1): 3396, 2934, 1670, 1638, 1594.

1H NMR (DMSO-d6, 400 MHz) δ: a 9.25 (1H, s), 9,10 (1H, d), 8,82 (1H, d), 8,39 (1H, t), compared to 8.26-of 8.25 (2H, m), the 7.43 (1H, t), 7,30 (2H, t),? 7.04 baby mortality (2H, d), to 6.95 (1H, t), of 6.75 (1H, s), 6,46 (2H, s), 5,09 (2H, s), 4,20-to 4.15 (1H, m), 1.93 and-or 1.77 (6H, m), 1,67 (1H, d), 1,36 is 1.20 (3H, m).

Mass spectrum (m/z): 458, 459, 460.

Example 40

Hydrochloride 3-[(3-phenylmethyl)pyrazole-5-yl]pyridine (Compound 39).

Yield: 73%.

IR (KBr, cm-1): 3056, 1611, 1559.

1H NMR (DMSO-d6, 400 MHz) δ: 9,18 (1H, s), 8,73 (2H, d), to 7.93 (1H, t), 7,35-7,22 (5H, m), 6,77 (1H, s), Android 4.04 (2H, s).

Mass spectrum (m/z): 236, 237.

Example 41

Hydrochloride 3-[(3-phenoxymethyl)pyrazole-5-yl]pyridine (Compound 40).

Yield: 65%.

IR (KBr, cm-1): 3035, 1601, 1562.

1H NMR (DMSO-d6, 400 MHz) δ: a 9.25 (1H, s), 8,77 (2H, s), of 7.97 (1H, t), 7,32 (2H, t), 7,12 (1H, s), 7,05 (2H, d), 6,97 (1H, t), of 5.17 (2H, s).

Mass spectrum (m/z): 252, 253, 254.

Example 42

3-[(3,5-Dimethylpyrazol-1-yl-methyl)pyrazole-5-yl]pyridine (Compound 41).

Yield: 93%.

IR (KBr, cm-1): 3080, 1559.

1H NMR (DMSO-d6, 400 MHz) δ: 13,30 (1H, users), 8,96 (1H, s), 8,49 (1H, s), 8,11 (1H, d), the 7.43 (1H, ears is .c), 6,63 (1H, s), of 5.81 (1H, s)to 5.17 (2H, s), of 2.28 (3H, s)2,07 (3H, s).

Mass spectrum (m/z): 254, 255, 256.

Example 43

3-[3-(2-Cyclohexylethyl)-pyrazole-5-yl]pyridine (Compound 42).

Yield: 76%.

IR (KBr, cm-1):

1H NMR (DMSO-d6, 400 MHz) δ: of 12.73 (1H, s), 8,98 (1H, s), 8,46 (1H, s), 8,11 (1H, d), 7,46-7,38 (1H, d), to 6.57 (1H, s), 2.63 in (2H, t), a 1.75-to 1.60 (5H, m), 1.56 to a 1.50 (2H, m), 1,25-1,08 (4H, m), 0,95-of 0.87 (2H, m).

Mass spectrum (m/z): 256, 257, 258.

Example 44

Bromide 1-(2-naphthyl-2-oxoethyl)-3-[(3-phenoxymethyl)pyrazole-5-yl]pyridinium (Compound 43).

Yield: 30%.

IR (KBr, cm-1): 3417, 2340, 1638, 1536, 1144.

1H NMR (DMSO-d6, 400 MHz) δ: 13,8 (1H, s), 9,58 (1H, s), the remaining 9.08-9,06 (1H, d), 8,95-8,93 (1H, d), cent to 8.85 (1H, s), 8,32 (1H, t), 8,25-8,23 (1H, d), 8,18-8,16 (1H, d), 8,10-with 8.05 (2H, m), 7,79-of 7.70 (2H, m), 7,33 (2H, t), 7,10 (1H, s), 7,06? 7.04 baby mortality (2H, d), 6,98 (1H, t), 6,63 (2H, s), 5,23 (2H, s).

Mass spectrum (m/z): 420, 421.

Example 45

Chloride 1-(phenylmethyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium (Compound 44).

Yield: 31%.

IR (KBr, cm-1): 3051, 1523, 1466.

1H NMR (DMSO-d6, 400 MHz) δ: 13,48 (1H, s), 9,63 (1H, s), 9,05-9,03 (1H, d), 8,91-of 8.90 (1H, d) of 8.15 (1H, t) of 7.55 (2H, m), 7,45-the 7.43 (3H, m), 7,34-of 7.25 (5H, m) 6,79 (1H, s), 5,88 (2H, s)4,06 (2H, s).

Mass spectrum (m/z): 326, 327, 328.

Example 46.

Chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(3-(-1-naphthyl)pyrazole-5-yl]pyridinium (Compound 45).

Yield: 22%.

IR (KBr, cm-1): 3057, 1671, 1517.

1H NMR (DMSO-d6, 400 MHz) δ: 13,60 (1H, s), 9,40 (1H, s) 8,97-of 8.95 (1H, d), 8,86 cent to 8.85 (1H, d), 8,23-8,18 (3H, m), 8,10-8,08 (1H, d), 7,87-7,86 (1H, d), 7,55-7,44 (4H, m), 7,40 (1, t), 6,55-of 6.52 (1H, s)6,40 (2H, s), of 4.54 (2H, s).

Mass spectrum (m/z): 410, 411, 412.

Example 47

Chloride 1-(2-phenyl-oxoethyl)-3-[3-(thienyl-2-yl-methyl)pyrazole-5-yl]pyridinium (Compound 46).

Yield: 22%.

IR (KBr, cm-1): 3068, 1691, 1519.

1H NMR (DMSO-d6, 400 MHz) δ: 13,55 (1H, s), 9,50 (1H, s), 9,01 (1H, d), 8,87 (1H, d), compared to 8.26 (1H, t) 8,07 (2H, m), 7,81 (1H, d), 7,68 (3H, t), 7,40 (2H, m), 6,78 (1H, s), of 6.49 (2H, s), 4,30 (2H, s).

Mass spectrum (m/z): 360, 361.

Example 48.

Chloride 1-(2-(5-methyl-2-thienyl)-2-oxoethyl)-3-[3-(2-phenylethyl)pyrazole-5-yl]pyridinium (Compound 47).

Yield: 24%.

IR (KBr, cm-1): 3068, 1661, 1450.

1H NMR (DMSO-d6, 400 MHz) δ: 13,33 (1H, s), for 9.47 (1H, s), 8,97-of 8.95 (1H, d), 8,87-8,86 (1H, d), compared to 8.26 is 8.22 (1H, t), 8,05-of 8.04 (1H, d), 7,31-7,14 (6H, m), 6,78 (1H, s)6,34 (2H, s), 2,98 (4H, s)at 2.59 (3H, s).

Mass spectrum (m/z): 388, 389, 390.

Example 49.

Chloride 1-(2-(5-methyl-2-thienyl)-2-oxoethyl)-3-[3-(3-phenoxypropan)pyrazole-5-yl]pyridinium (Compound 48).

Yield: 30%.

IR (KBr, cm-1): 3057, 1665, 1452.

1H NMR (DMSO-d6, 400 MHz) δ: 13,34 (1H, s), 9,48 (1H, s), 8,99-8,97 (1H, d), 8,23 (1H, t), 8,05-of 8.04 (1H, d), 7,28 (1H, t), 7,15-7,14 (1H, d), 6,94-6,92 (3H, d) 6,83 (1H, s), 6.35mm (2H, s), was 4.02 (2H, t), of 2.86 (2H, t), of 2.27 (2H, t).

Mass spectrum (m/z): 418, 419, 420.

Example 50.

Bromide 1-(isopropyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium (Compound 49).

Yield: 15%.

IR (KBr, cm-1): 3418, 2364, 1648.

1H NMR (DMSO-d6, 400 MHz) δ: 9,43 (1H, s), which is 9.09-9,07 (1H, d), 8,88-8,86 (1H, d), 8,16-8,13 (1H, m), of 7.36-7,14 (5H, m), at 6.84 (1H, s)4,06 (2H, s), 1,65-to 1.63 (6H, d).

Mass spectrum (m/z): 278, 279, 280.

Example 51.

Chloride 1-(2-(5-methyl-2-thienyl)-2-oxoethyl)-3-[(3-phenylthiomethyl)pyrazole-5-yl]pyridinium (Compound 50).

Yield: 31%.

IR (KBr, cm-1): 3365, 1650, 1452.

1H NMR (DMSO-d6, 400 MHz) δ: of 13.58 (1H, s), 9,46 (1H, s), 8,98-8,96 (1H, d), 8,87 cent to 8.85 (1H, d), 8,25-8,21 (1H, m), 8,04-8,03 (1H, d), 7,37-7,30 (5H, m), 7,15-7,14 (1H, d), to 6.88 (1H, s), 6,32 (2H, s), 4,36 (2H, s), 2,59 (3H, s).

Mass spectrum (m/z): 406, 407, 408, 409.

Example 52.

Chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(3-(N-methyl-indole-3-ylmethyl)pyrazole-5-yl]pyridinium (Compound 51).

Yield: 20%.

IR (KBr, cm-1): 3070, 1669, 1410.

1H NMR (DMSO-d6, 400 MHz) δ: to 9.32-of 9.30 (1H, m), 9,00-of 8.92 (2H, m), 8,77-8,76 (1H, d), 8,19-of 8.15 (2H, m), 8,10-8,07 (1H, m), 7,47 was 7.45 (1H, d), 7,39-to 7.35 (3H, m) 7,19-7,10 (2H, m), 7.03 is-7,00 (1H, t), 6,34 (2H, s), 4,22 (1H, ), with 3.79 (3H, s)

Mass spectrum (m/z): 413.

Example 53.

Bromide 1-(2-naphthyl-2-oxoethyl)-3-[(3-methyl)pyrazole-5-yl]pyridinium (Compound 52).

Yield: 38%.

IR (KBr, cm-1): 3066, 1675, 1518.

1H NMR (DMSO-d6, 400 MHz) δ: 13,25 (1H, s)9,533 (1H, s) 9,02-9,0 (1H, d), 8,92-8,91 (1H, d), 8,84 (1H, s), 8,32-8,04 (5H, m), 7,79-of 7.70 (2H, m), of 6.75 (1H, s), 6,63 (2H, s), of 2.33 (3H, s).

Mass spectrum (m/z): 328, 329, 330.

Example 54.

Chloride 1-(2-(1,4-benzodioxan-6-yl-amino-2-oxoethyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium (Compound 53).

Yield: 32%.

IR (KBr, cm-1): 3445, 3068, 1678.

1H NMR (DMSO-d6, 400 MHz) δ: 13,45 (1H, s), 10,61 (1H, s), for 9.47 (1H, s), 8,97-of 8.95 (1H, d), 8,91-8,89 (1H, d), and 8.2 (1H, t), 7,34-7,19 (6H, m), 6,99-6,97 (1H, d), 6,84-6,82 (H, d), 6,72 (1H, s), 5,61 (2H, s), is 4.21 (4H, s)4,06 (2H, s).

Mass spectrum (m/z): 427, 428, 429.

Example 55.

Chloride 1-(2-Tien-2-yl-2-oxoethyl)-3[(3-phenyl)pyrazole-5-yl]-5-bromopyridine (Compound 54).

Yield: 31%.

IR (KBr, cm-1)

1H NMR (DMSO-d6, 400 MHz) δ: 9,63 (1H, s), 9,36 (1H, s), was 9.33 (1H, s), 8,27-8,24 (2H, m), 7,81-7,79 (2H, d), EUR 7.57-7,52 (3H, m), 7,46-7,42 (2H, m), 6,40 (2H, s).

Mass spectrum (m/z): 426, 427, 428.

Example 56.

Chloride 1-(2-Tien-2-yl)-2-oxoethyl)-3-[(3-phenyl)pyrazole-5-yl]chinoline (Compound 55).

Yield: 26%.

IR (KBr, cm-1)

1H NMR (DMSO-d6, 400 MHz) δ: 10,18 (1H, s), 9,81 (1H, s) 8,45-to 8.40 (3H, m), 8,29-of 8.28 (1H, d), 8,21 (1H, t), 8,08 (1H, t), 7,87-a 7.85 (2H, d), EUR 7.57-of 7.55 (3H, m), 7,50 was 7.45 (2H, m), of 6.96 (2H, s).

Mass spectrum (m/z): 396, 397, 398.

Example 57.

3-[(3-phenyl)pyrazole-5-yl)]quinoline (Compound 56).

Yield: 70%.

1H NMR (DMSO-d6, 400 MHz) δ: of 9.45 (1H, users), is 8.75 (1H, s), with 8.05 (2H, d), 7,87 (2H, users), to 7.77 (1H, t), the 7.65 (1H, t), 7,55 was 7.45 (3H, m), 7,39 (1H, users).

Mass spectrum (m/z): 272 (M++1)

Cosmetic product

The drug for use in cosmetic application may contain one or more concentrates connection cosmetically acceptable carrier. The number of compounds according to the invention preferably will fluctuate in the range between 0.005 and 50% by weight (unless otherwise stated, all fractions are expressed in weight percent, more preferably between 0.20% 5.0% weight./weight. Composition is Yu should be applied based on the requirements for the affected area.

Suitable transfer system or media for storage and/or delivery of the new compounds according to this invention can be designed in the form of a lotion, liquid, ointments, gels, creams, spray, poultices or other forms, and preferably they will have a lipophilic, hydrophilic or amphiphilic character.

Suitable carrier materials include petrolatum, triglycerides, various esters, fatty alcohols, fatty acids, alkalophile and ethanol, among which polyethylenglycol and polypropylenglycol are most preferred; if desired, are also suitable compatible combinations of data carriers.

In addition, migration tools are present, if necessary, for desired delivery system. Migration tools or media may also contain additional agents in accordance with the usual practice. For example, the final composition may contain various softeners, emulsifiers, alcohol, dyes, perfume, thickeners such as xanthan gum), preservatives, humectants, surfactants (anionic, cationic, nonionic, amphoteric, individually or in combination), agents modifying the differentiation and/or proliferation and/or pigmentation, antiparasitics agents, dispersing agents, mufflers, gelling agents that hydrate the dominant agents additional antioxidants, conventional Botanical extracts, such as, for example, derived from aloe, citrus, witch hazel, chamomile, and the like, for example, with astringent, antiseptic, sunscreen effect or properties, giving a tan, leather dye, silicones, exfoliating agents, keratolytic agents, retinoids, amplifiers permeability of the skin, vitamins, thrombolytic agents, anticoagulation agents, agents to protect capillaries, hormones, antimicrobial agents, antiviral agents, steroidal anti-inflammatory agents, anesthetics, protivoseborainey agents, agents dandruff agents against acne, anti-free radical agents, analgesics, lipophilic compounds, antihistamine agents, insect repellent, cooling the skin compounds, lubricating agents, antifungal agents, or mixtures thereof. The composition additionally may include amplifiers permeability, such as, but not limited to, oleic acid, DMSO (dimethylsulfoxide), alcohols, N-organic, dimethyldithiocarba. It can also include one or more additional active ingredients such as anti-inflammatory agents, antibiotics, astringents, growth factors, Tocopherols, retinol, scavengers of free radicals.

The following does not exhaust unicefusa examples of cosmetic compositions according to the present invention

Example 58

The compound of the invention0.3 % weight/weight
Oleic acid10.0 % weight/weight
Propylene glycol70,0 % weight/weight
Tween 200.1% weight/weight
Absolute ethanol as necessary before100 % weight/weight

Example 59

The compound of the invention0.3 % weight/weight
Oleic acid10.0 % weight/weight
Colloidal silicon dioxide6,0 % weight/weight
Tween 800.1% weight/weight
Caprylic capric triglyceride, as you need to100 % weight/weight

Independently in the composition optionally may contain cosmetically acceptable organic fatty acid in amount, preferably in a biologically active amount from 0.1% to 10.0%; the added fatty acid is a preferred ingredient.

The action of the compounds of the invention synergistically improves when combined with a humectant, emollient, additional antioxidants or anti-inflammatory agents.

Example 60

The compound of the invention0.4 % weight/weight
Fatty acid4,0 % weight/weight
Mineral oil5,0 %
Isolatedstore1.0% weight/weight
Antioxidant0.05% weight/weight
Xanthan gum0.2% weight/weight
Glycerin50,0% weight/weight
Diazolidinylurea0.2% weight/weight
Extract lemon peel0.02% weight/weight
Alcohol2.0% weight/weight
Purified water100,0% weight/weight

It is expected that the addition of humectants and emollients agent to antioxidant compositions will help restore moisture and maintain hydration considered skin. It is assumed that improved hydration of the skin will be how to increase the absorption of scavenger of free radicals skin, and to help deliver scavenger of free radicals to the active site.

Examples of softening agents that can be used are: mineral oil, petrolatum, paraffin, ceresin, ozokerite, microcrystalline wax, perhydrosqualene dimethylpolysiloxene, methylphenylpolysiloxane, the silicone copolymer is a silicone-glycol-triglyceride esters, acetylated monoglycerides, ethoxylated glycerides, alkalemia esters of fatty acids, fatty acids and alcohols, lanolin and lanolin derivatives, polyhydrogenated esters of alcohols, steady derived beeswax, polyhydrogenated alcohols and polyethers and amides of fatty acids. Although this region is famous for various mitigation tools that can be used in the present invention, the preferred softening agent is silicone.

Suitable are known in the field moisturizers that increase the hydration of the skin when applied topically, such as polyhydrogenated alcohols. Examples of suitable humectants are glycerin, propylene glycol, butyleneglycol, diglycerin or their ester derivatives. However, the preferred humectant is glycerin.

Local preparations of the present invention may contain an antioxidant, in addition to the compounds of the invention, or a combination of antioxidants, such as antioxidant mixture. It is implied that the term "antioxidant"as used herein, includes both single antioxidant or mixture of antioxidants. The antioxidant can also be entered in a variety of delivery vehicles to facilitate local use.

To obtain the excellent local composition in the form of the remov, emulsions, lotions or gels such compositions may include from about 0.001 wt.% to about 50 wt.% the antioxidant.

The local composition of the present invention can be made in the form of lotions and creams.

A scavenger of free radicals can be combined with most of emulsifiers, which are used to obtain lotions, creams and other appropriate means of delivery. Emulsifying agents can be cationic, anionic, nonionic, amphoteric or a combination of both. Preferred are nonionic emulsifiers. Examples of commercially available nonionic emulsifiers are sorbite, alkoxysilane fatty alcohols and alkylpolyglycoside. Anionic emulsifiers may include Soaps, alkyl sulphates, monoalkyl and dialkylphosphate, alkylsulfonate and arylisocyanate, amphoteric emulsifier, which can be used is a chloride of Lakshminarayanan.

Appropriate means of delivery of compositions of the present invention may also include thickeners. Examples of suitable thickeners include cellulose derivatives such as hydroxyethylcellulose and hydroxypropylcellulose, and also polymers of polyacrylic acid.

Examples of preservatives that are suitable for use in the compositions include aliphatic alcohols, especially what about ethanol and benzyl alcohol; parabens, sorbates, urea derivatives and isothiazolinone.

Lotions or creams according to the present invention can be obtained using conventional homogenization methods known to experts in this field. It is also possible using the method of microfluidizer, which includes joint mixing the aqueous phase and oil phase of such creams and lotions in the high-pressure homogenizer, which dramatically reduces the particle size of the emulsion to about several microns compared with those in creams and lotions, obtained without using high pressure. Microfluidizer allows you to get excellent stable creams and lotions containing effective amounts of the compounds, without the use of traditional emulsifiers and surface-active substances.

Compositions for topical application according to the present invention can also be obtained in the form of a microemulsion, which is a subsection of emulsions; oil that can be used are mineral oil and silicone oil. Examples of alcohols that can be used are cetyl alcohol, isostearoyl alcohol, stearyl alcohol, dodecanol and dodecanol. Nonionic surfactants may constitute esters of fatty acids, esters of fatty who alcohols or ethoxylated alcohols. Examples of nonionic surfactants are polyethylene glycol, isopropylmyristate acilitation, polypropylenglycol, sorbite and isopropylacetate.

Example 61

The compound of the invention0.2 % weight/weight
Fatty acid1.5 % weight/weight
Surfactant3.0 % weight/weight
The co-solvent70,0%
Purified water as needed to100 % weight/weight

Compositions for topical application according to the invention can be obtained in the form of emulsions of oil-in-water or water-in-oil. The composition can also be in the form of a multiphase emulsion, such as an emulsion of the type water-in-oil-in-water.

The composition of the invention can also be obtained in the form of liposomal drugs. In such compositions the solution of the connection may be located inside the liposomal vesicles, where the wall of the liposome is a phospholipid or other suitable fat (for example, the lipids of the skin). To obtain a composition for topical application of liposomes can be added to any of the above-described system media in accordance with the methods of receipt, use and compositions local liposomes.

Example 62

The compound of the invention0.4 % weight/weight
The phospholipid6,0 % weight/weight
Antioxidants0.5 % weight/weight
Ethanol15,0%
Hydrophilic environment, as you need to100 % weight/weight

Solutions of compounds and antioxidants can also be captured in polymer vesicles, where the wall includes a suitable polymeric material such as gelatin, crosslinked gelatin, polyamide, polyacrylates, and the like, with the formation of vesicles, which is then injected into the composition for local application.

The composition according to the present invention can be used for one or more of the following cosmetic applications, namely (a) smooth and prevent wrinkles, (b) smoothing and prevent the formation of facial wrinkles, c) promotion of growth of the epidermis, d) sun protection of the skin, (e) recovery and prevention of discoloration of the skin, (f) removing and preventing the formation of age spots, g) conditioning and prevention of dry skin, h) removal and prevention of traces of braces, i) removal and prevention of defects of the skin, j) skin care/healthy skin condition (k) removal and prevention of senile xerosis, ) of the skin and prevent sunburn, m) the prevention and recovery of loss of collagen, n) improvement in skin texture, o) improvement of skin tone, p) increasing the thickness of the skin, q) reduce pore size, r) restoration of skin luster, s) minimize signs of fatigue, t) reduce coal rashes, w) treatment of telangiectasias and (v) improve the aesthetic appearance of hair and nails.

The pharmaceutical composition

Pharmaceutical compositions effective for the removal of free radicals and/or inhibition of AGE, can be obtained using a pharmaceutically effective amount of the compounds of General formula I, alone or in combination. The number of compounds according to the invention preferably will range between 0.00001 and 90 % by weight. These pharmaceutical drugs are offered only as examples and in no way limit the scope of the invention.

Oral preparations

Oral drugs can be administered in the form of a solid dosage formulation of dosage forms, such as pills, powders, sachets, or discrete units such as tablets or capsules, and the like. Other oral input pharmaceutical products include single-phase and two-phase preparative liquid dosage forms or in a form ready for use, or in a form suitable for subsequent recovery vlahos is the actual content, such as mixtures, syrups, suspensions or emulsions. Additionally, the preparations may contain diluents, dispersing agents, buffers, stabilizers, surfactants, preservatives, chelating agents and/or other applicable pharmaceutical additives. You can use water or non-aqueous carriers or combinations thereof, and, if desired, they may contain suitable sweetener, flavoring agent or similar substances. In the case of a suspension or emulsion, in addition, may be suitable thickener or suspendisse agent. Alternatively, compounds can be entered as such in its pure form, not associated with other additives, for example, in the form of capsules or sachets. Also they can be administered together with a carrier. The pharmaceutical preparations may have slowed, delayed or controlled by the degree of release of active ingredients, which is a matrix or diffuse controlled by the system.

When the compound of the present invention, or its salt, or a suitable complexes are present in discrete preparative dosage form such as tablet, it can optionally contain medical inert excipients used in this field. Can also be used diluents, such as starch, lactose, dicalcium phosphate, talc, stearate mA is of polymeric substances, such as methyl cellulose, fatty acids and their derivatives, sodium starch glycolate, etc.

Example 63

Receiving oral preparative dosage forms

A typical tablet may have the following composition:

The active ingredient of the General formula IAn effective amount
Lactose100 mg
Microcrystalline cellulose51 mg
Starch60 mg
Polivinilpirolidon (30)2 mg
Talc1.5 mg
Magnesium stearate1.0 mg

or

The active ingredient of the General formula IAn effective amount
Lactose130 mg
Starch75 mg
Polivinilpirolidon (30)2 mg
Talc1.5 mg
Magnesium stearate1.0 mg

Parenteral drugs

For parenteral administration the compounds or their salts, or suitable complexes may Pris is estvovati in sterile media, which can be an aqueous or non-aqueous media, or a combination of both. Examples of carriers include water, etiloleat, oil and derivatives, polyhydric alcohols, glycols and their derivatives. They may contain common for injectable additives, such as stabilizers, soljubilizatory, pH modifiers, buffers, antioxidants, co-solvents, complexing agents, modifiers tone solution, etc.

Some suitable additives are, for example, tartrate, citrate or a similar buffer, alcohol, sodium chloride, dextrose and high molecular weight polymers. Another alternative is to restore moisture sterile powder. The connection can be introduced in the form of injections more than once a day, or in the form of intravenous injection/infusion, or in the form of a suitable depot of the drug.

Example 64

The preparation for parenteral administration:

The active ingredient of the General formula IAn effective amount
Polyethylene glycol (400)20,0 % weight/about
Metabisulphite sodium0.01 % weight/about
Isotonic saline/WFIas you need to 100 %

Other medicines.

For dermatol the policy application and to change the color of teeth recommended drugs are lotions, the mouthwash for mouth and tooth paste containing a suitable amount of the compounds of General formula I.

The above examples are presented only as an illustration and in no way limit the scope of the invention.

1. The compound represented by formula (I)and its pharmaceutically or cosmetically acceptable salt

where R1selected from linear or branched (C1-C12)alkyl, (C3-C7)cycloalkyl, phenyl, naphthyl,3C4C5or C8heteroaryl, where one or more heteroatoms, when they are present, are independently selected from O, N, or S, and optionally substituted, where the substituents are selected from the first group comprising halogen, hydroxy, nitro, cyano, amino, oxo and the oxime, or from a second group including linear or branched (C1-C8)alkyl where the Deputy from the specified second group optionally substituted by R10or where heteroaryl substituted-CH2-C(O)-2-tanila;

Y is absent or selected from the group consisting of (C1-C8)alkyl-Z, or (C2-C8)alkyl, where Z is selected from sulfur, oxygen or nitrogen;

A and b are independently selected from N, NH, NR6, sulfur, oxygen with the formation of heteroaromatic ring system;

R2, R3/sub> and R4independently selected from a first group comprising hydrogen, halogen, or R3and R4in adjacent positions form a phenyl ring;

R5absent or selected from the group comprising-CH2-phenyl, -CH2(CO)R7, -CH2(CO)other8and-CH2(CO)NR8R9that is not necessarily replaced by R10;

R6, R7, R8and R9independently selected from the group including linear or branched (C1-C8)alkyl, (C3-C7)cycloalkyl, C5heteroseksualci, benzylpiperidine, phenyl, naphthyl, heteroaryl, alkylether, substituted, or R8and R9form a piperidine, or R8means 3,4-atlanticcity, where the substituents specified group optionally substituted by R10and heteroaryl means3C4With5or C8heteroaryl, where one or more heteroatoms, when they are present, are independently selected from O, N, or S;

R10selected from halogen, hydroxy, nitro, cyano, amino, oxo, perhalogenated (C1-C6or oxime;

X is a halide ion;

provided that, when the groups/substituents are present in the same or adjacent carbon atoms or nitrogen, together they may not necessarily form a five - or six-, or semiline ring, not battelino containing one or more double bonds and optionally containing one or more heteroatoms, selected from O, N, or S.

2. The compound according to claim 1, where the specified pharmaceutically/cosmetically acceptable salts are salts of carboxylic acids selected from the salts of alkali metals and alkaline earth salts of metals; salts of organic bases selected from lysine, arginine, guanidine, diethanolamine and choline; salt, ammonium salt or substituted ammonium salt of aluminum; or an acid additive salt selected from the group including sulfates, nitrates, phosphates, perchlorates, borates, hydrogenogenic, acetates, tartratami, maleate, citrates, succinate, palmoate, methansulfonate, benzoate, salicylates, hydroxynaphthoate, bansilalpet, ascorbate, glycerophosphate and Ketoglutarate.

3. The compound according to claim 1, where R1represents a substituted or unsubstituted group selected from linear or branched (C1-C12)alkyl, (C3-C7)cycloalkyl, geterotsiklicheskie, phenyl, naphthyl or heteroaryl, where one or more heteroatoms, if present, is independently selected from O, N, or S.

4. The compound according to claim 1, where a and b are independently selected from NH and NR6.

5. The compound according to claim 1, where R2, R3and R4independently selected from the group comprising hydrogen, halogen.

6. The compound according to claim 1, where R5is absent or selected from the group-CH2(CO)R7and-CH2 (CO)other8and they all may be optionally substituted by R10.

7. The compound according to claim 1, selected from the group comprising the following compounds or their pharmaceutically acceptable salts:

a) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium;

b) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(3-phenylmethyl)oxazol-5-yl]pyridinium;

c) dibromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[3-{1-(2-Tien-2'-yl)-2-oxoethylidene-4-thio}methyl-pyrazole-5-yl]pyridinium;

d) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[3-{1-(3,5-dimethylpyrazol-1-yl)methyl}pyrazole-5-yl]pyridinium;

e) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[{3-phenylmethyl}-1-{2-pyridyl}pyrazole-5-yl]pyridinium;

f) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[3-{(3,5-dimethylpyrazol-1-yl)methyl-1-pyridyl} pyrazole-5-yl]pyridinium;

g) bromide 1-[2-(cyclopropylamino)-2-oxoethyl]-3-[3-{(3,5-dimethylpyrazol-1-yl)methyl}-pyrazole-5-yl]pyridinium;

h) bromide 1-{2-(4-nitro-2-thienyl-2-oxoethyl}-3-[3-{(3,5-dimethylpyrazol-1-yl)ethyl}pyrazole-5-yl]pyridinium;

i) chloride 1-(2-cyclopropylamino-2-oxoethyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium;

j) dibromide 3,5-bis-[1-(2-Tien-2'-yl-2-oxoethyl)pyridine-3-yl]pyrazole;

k) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(1-phenyl-3-phenylmethyl)pyrazole-5-yl]pyridinium;

l) chloride 1-(2-(5'-methyl-2-thienyl)-2-oxoethyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium;

m) is lorid 1-(2-Tien-2'-yl-2-oxoethyl-3-[1-phenyl-3-{(3,5-dimethylpyrazol-1-yl)methyl)}pyrazole-5-yl]pyridinium;

n) bromide 1-(2-phenyl-2-oxoethyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium;

o) chloride 1-(2-cyclopropylamino-2-oxoethyl)-3-[(1-phenyl-3-phenylmethyl)pyrazole-5-yl]pyridinium;

R) bromide 1-(2-(4-benzyl-1-piperidinyl)-2-oxoethyl)-3-[(3-phenoxymethyl)pyrazole-5-yl]pyridinium;

q) chloride 1-(2-phenyl-2-oxoethyl)-3-[(3-(3,5-dimethylpyrazol-1-yl)methyl)pyrazole-5-yl]pyridinium;

r) chloride 1-(2-(5-methyl-2-thienyl)-2-oxoethyl)-3-[(3-(3,5-dimethylpyrazol-1-yl)methyl)pyrazole-5-yl] pyridinium;

s) chloride 1-(2-phenyl-2-oxoethyl)-3-[(1-phenyl-3-phenylmethyl)pyrazole-5-yl]pyridinium;

t) chloride 1-(2-(5-methyl-2-thienyl)-2-oxoethyl)-3-[(3-(2-cyclohexylethyl)pyrazole-5-yl]pyridinium;

u) chloride 1-(2-cyclopropylamino-2-oxoethyl)-3-[(3-(2-cyclohexylethyl)pyrazole-5-yl]pyridinium;

v) chloride 1-(2-phenyl-2-oxoethyl)-3-[(3-(2-cyclohexylethyl)pyrazole-5-yl]pyridinium;

w) chloride 1-(2-cyclopropylamino-2-oxoethyl)-3-[(1-cyclohexyl-3-phenylmethyl)pyrazole-5-yl]pyridinium;

x) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(3-phenoxymethyl)pyrazole-5-yl]pyridinium;

y) chloride 1-[2-(1-adamantylamine)-2-oxoethyl]-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium;

z) bromide 1-(2-phenyl-2-oxoethyl)-3-[{3-(3,5-dimethylpyrazol-1-yl)methyl)}-1-phenylpyrazol-5-yl] pyridinium;

AA) bromide 1-(2-(4-nitro-2-thienyl)-2-oxoethyl)-3-[(1-cyclohexyl-3-(3,5-dimethylpyrazol-1-yl)methyl)pyrazole-5-yl]Piri is ine;

bb) bromide 1-(2-(4-nitro-2-thienyl)-2-oxoethyl)-3-[(3-(2-cyclohexylethyl)pyrazole-5-yl] pyridinium;

cc) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(1-phenyl-3-phenoxymethyl)pyrazole-5-yl]pyridinium;

dd) bromide 1-(2-(4-nitro-2-thienyl)-2-oxoethyl)-3-[(1-phenyl-3-phenylmethyl)pyrazole-5-yl]pyridinium;

her) chloride 1-(2-cyclopropylamino-2-oxoethyl)-3-[(3-phenoxymethyl)pyrazole-5-yl]pyridinium;

ff) chloride 1-(2-cyclopropylamino-2-oxoethyl)-3-[(1-cyclohexyl-3-(3,5-dimethylpyrazol-1-yl)methyl)pyrazole-5-yl]pyridinium;

gg) bromide 1-(2-(5-chloro-2-thienyl)-2-oxoethyl)-3-[(3-phenoxymethyl)pyrazole-5-yl]pyridinium;

hh) chloride 1-(2-phenyl-2-oxoethyl)-3-[(1-phenyl-3-phenoxymethyl)pyrazole-5-yl]pyridinium;

ii) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(1-cyclohexyl-3-(3,5-dimethylpyrazol-1-yl)methyl)pyrazole-5-yl]pyridinium;

jj) bromide 1-(2-cyclopropylamino-2-oxoethyl)-3-[(1-phenyl-3-phenoxymethyl)pyrazole-5-yl]pyridinium;

kk) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(1-phenyl-3-(2-cyclohexylethyl)pyrazole-5-yl]pyridinium;

ll) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(1-cyclohexyl-3-phenoxymethyl)pyrazole-5-yl]pyridinium;

mm) of the hydrochloride of 3-[(3-phenylmethyl)pyrazole-5-yl]pyridine;

nn) of the hydrochloride of 3-[(3-phenoxymethyl)pyrazole-5-yl]pyridine;

OO) 3-[(3,5-dimethylpyrazol-1-yl-methyl)pyrazole-5-yl]pyridine;

PP) 3-[3-(2-cyclohexyl-ethyl)-pyrazole-5-yl]pyridi is;

qq) bromide 1-(2-naphthyl-2-oxoethyl)-3-[(3-phenoxymethyl)pyrazole-5-yl]pyridinium;

rr) chloride 1-(phenylmethyl)-3[(3-phenylmethyl)pyrazole-5-yl]pyridinium;

ss) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(3-(-1-naphthyl)pyrazole-5-yl]pyridinium;

tt) chloride 1-(2-phenyl-2-oxoethyl)-3-[3-(thienyl-2-yl-methyl)pyrazole-5-yl]pyridinium;

uu) chloride 1-(2-(5-methyl-2-thienyl)-2-oxoethyl)-3-[3-(2-phenylethyl)pyrazole-5-yl]pyridinium;

vv) chloride 1-(2-(5-methyl-2-thienyl)-2-oxoethyl)-3-[3-(3-phenoxypropan)pyrazole-5-yl]pyridinium;

ww) bromide 1-(isopropyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium;

XX) chloride 1-(2-(5-methyl-2-thienyl)-2-oxoethyl)-3-[(3-thienylmethyl)pyrazole-5-yl]pyridinium;

yy) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(3-(N-methyl-indole-3-ylmethyl)pyrazole-5-yl]pyridinium;

zz) bromide 1-(2-naphthyl-2-oxoethyl)-3-[(3-methyl)pyrazole-5-yl]pyridinium;

AAA) chloride 1-(2-(1,4-benzodioxan-6-ylamino-2-oxoethyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium;

bbb) chloride 1-(2-Tien-2'-yl)-2-oxoethyl)-3-[(3-phenyl)pyrazole-5-yl]-5-bromopyridine;

CCC) chloride 1-(2-Tien-2'-yl)-2-oxoethyl)-3-[(3-phenyl)pyrazole-5-yl]chinoline and

ddd) 3-[(3-phenyl)pyrazole-5-yl)]quinoline.

8. The method of obtaining compounds of General formula (I)as defined in claim 1, comprising the following stages:

(a) obtaining the corresponding 1,3-diketo connection interaction unsubstituted what s/substituted acetylpyridine with alkylamine/akrilovye esters in a suitable base or interaction unsubstituted/substituted arolovich esters with unsubstituted/substituted in a suitable arylmethylidene basis;

(b) cyclization of the product obtained at stage (a), and, optionally,

(c) quaternization of the substituted pyridine, obtained in stage (b), the quaternization agent in alcohol and/or high-boiling solvent at the boiling point under reflux for onset 6 to 48 h to obtain the target compounds.

9. The pharmaceutical composition inhibiting the formation or accumulation of AGE and absorbing free radicals in mammalian cells, comprising pharmaceutically effective amount of one or more compounds of General formula (I)as defined according to claim 1, or pharmaceutically acceptable salt(s) in a mixture with a pharmaceutically acceptable carrier, diluent, solvent or excipient.

10. The pharmaceutical composition according to claim 9 in the form of oral medication.

11. The pharmaceutical composition according to claim 9, where the specified acceptable carrier, diluent, solvent or excipient selected from the group comprising starch, lactose, polivinilpirolidon (K-30), talc and magnesium stearate.

12. The pharmaceutical composition according to claim 9 in the form of parenteral drug.

13. The method of receiving parenteral drug indicated in paragraph 12, including the dissolution of one or more compounds of General formula (I)as defined according to claim 1, in polyethylene glycol 400 and the dilution obtained in this clicks the zoom solution of saline or water to the desired concentration.

14. The pharmaceutical composition according to claim 9 in the form of a lotion, mouthwash for mouth and tooth paste.

15. The pharmaceutical composition according to claim 9, where the specified connection is selected from a group including:

a) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

b) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(3-phenylmethyl)oxazol-5-yl]pyridinium or its pharmaceutically acceptable salt;

c) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[3-{1-(2-Tien-2'-yl)-2-oxoethylidene-4-thio}methyl-pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

d) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[3-{1-(3,5-dimethylpyrazol-1-yl)methyl}pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

e) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[{3-phenylmethyl}-1-{2-pyridyl} pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

f) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[3{(3,5-dimethylpyrazol-1-yl)methyl-1-pyridyl}pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

g) bromide 1-[2-(cyclopropylamino)-2-oxoethyl]-3-[3-{(3,5-dimethylpyrazol-1-yl)methyl}pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

h) bromide 1-{2-(4-nitro-2-thienyl)-2-oxoethyl}-3-[3{(3,5-dimethylpyrazol-1-yl)ethyl}pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

i) chloride 1-(2-cyclopropylamino-2-oxoethyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

j) dibromide 3,5-bis-[1-(2-Tien-2'-yl-2-oxoethyl)pyridine-3-yl]pyrazole or its pharmaceutically acceptable salt;

k) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(1-phenyl-3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

l) chloride 1-(2-(5'-methyl-2-thienyl)-2-oxoethyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

m) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[1-phenyl,3-{(3,5-dimethylpyrazol-1-yl)methyl)}pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

n) bromide 1-(2-phenyl-2-oxoethyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

o) chloride 1-(2-cyclopropylamino-2-oxoethyl)-3-[(1-phenyl-3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

R) bromide 1-(2-(4-benzyl-1-piperidinyl)-2-oxoethyl)-3-[(3-phenoxymethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

q) chloride 1-(2-phenyl-2-oxoethyl)-3-[(3-(3,5-dimethylpyrazol-1-yl)methyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

r) chloride 1-(2-(5-methyl-2-thienyl)-2-oxoethyl)-3-[(3-(3,5-dimethylpyrazol-1-yl)methyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

s) chloride 1-(2-phenyl-2-oxoethyl)-3-[(1-phenyl-3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

t) chloride 1-(2-(5-methyl-2-thienyl)-2-oxoethyl)-3-[(3-(2-cyclohexylethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

u) chloride 1-(2-cyclopropylamino-2-oxoethyl)-3-[(3-(2-cyclohexylethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

v) chloride 1-(2-phenyl-2-oxoethyl)-3-[(3-(2-cyclohexylethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

w) chloride 1-(2-cyclopropylamino-2-oxoethyl)-3-[(1-cyclohexyl-3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

x) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(3-phenoxymethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

y) chloride 1-[2-(1-adamantylamine)-2-oxoethyl]-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

z) bromide 1-(2-phenyl-2-oxoethyl)-3-[{3-(3,5-dimethylpyrazol-1-yl)methyl)}-1 phenylpyrazol-5-yl]pyridinium or its pharmaceutically acceptable salt;

AA) bromide 1-(2-(4-nitro-2-thienyl)-2-oxoethyl)-3-[(1-cyclohexyl-3-(3,5-dimethylpyrazol-1-yl)methyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

bb) bromide 1-(2-(4-nitro-2-thienyl)-2-oxoethyl)-3-[(3-(2-cyclohexylethyl)pyrazole-5-yl]pyridinium or f is rmaceuticals acceptable salt;

cc) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(1-phenyl-3-phenoxymethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

dd) bromide 1-(2-(4-nitro-2-thienyl)-2-oxoethyl)-3-[(1-phenyl-3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

her) chloride 1-(2-cyclopropylamino-2-oxoethyl)-3-[(3-phenoxymethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

ff) chloride 1-(2-cyclopropylamino-2-oxoethyl)-3-[(1-cyclohexyl-3-(3,5-dimethylpyrazol-1-yl)methyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

gg) bromide 1-(2-(5-chloro-2-thienyl)-2-oxoethyl)-3-[(3-phenoxymethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

hh) chloride 1-(2-phenyl-2-oxoethyl)-3-[(1-phenyl-3-phenoxymethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

ii) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(1-cyclohexyl-3-(3,5-dimethylpyrazol-1-yl)methyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

jj) bromide 1-(2-cyclopropylamino-2-oxoethyl)-3-[(1-phenyl-3-phenoxymethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

kk) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(1-phenyl-3-(2-cyclohexylethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

ll) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(1-cyclohexyl-3-phenoxy ethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

mm) of the hydrochloride of 3-[(3-phenylmethyl)pyrazole-5-yl]pyridine or its pharmaceutically acceptable salt;

nn) of the hydrochloride of 3-[(3-phenoxymethyl)pyrazole-5-yl]pyridine or its pharmaceutically acceptable salt;

OO) 3-[(3,5-dimethylpyrazol-1-yl-methyl)pyrazole-5-yl]pyridine or its pharmaceutically acceptable salt;

PP) 3-[3-(2-cyclohexylethyl)-pyrazole-5-yl]pyridine or its pharmaceutically acceptable salt;

qq) bromide 1-(2-naphthyl-2-oxoethyl)-3-[(3-phenoxymethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

rr) chloride 1-(phenylmethyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

ss) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(3-(1-naphthyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

tt) chloride 1-(2-phenyl-2-oxoethyl)-3-[3-(thienyl-2-yl-methyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

uu) chloride 1-(2-(5-methyl-2-thienyl)-2-oxoethyl)-3-[3-(2-phenylethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

vv) chloride 1-(2-(5-methyl-2-thienyl)-2-oxoethyl)-3-[3-(3-phenoxypropan)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

ww) bromide 1-(isopropyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

XX) chloride 1-(2-(5-methyl-2-thienyl)-2-oxoethyl)-3-[(-thienylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

yy) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(3-(N-methyl-indole-3-ylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

zz) bromide 1-(2-naphthyl-2-oxoethyl)-3-[(3-methyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

AAA) chloride 1-(2-(1,4-benzodioxan-6-ylamino-2-oxoethyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

bbb) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(3-phenyl)pyrazole-5-yl]-5-bromopyridine or its pharmaceutically acceptable salt;

CCC) chloride 1-(2-Tien-2'-yl)-2-oxoethyl)-3-[(3-phenyl)pyrazole-5-yl]chinoline or its pharmaceutically acceptable salt and

ddd) 3-[(3-phenyl)pyrazole-5-yl)]quinoline or its pharmaceutically acceptable salt.

16. The use of compounds represented by formula (I)or its pharmaceutically acceptable salt

to obtain medicines used for the destruction of accumulated AGE in the treatment of diabetic eye diseases and age-related diseases caused by the accumulation of AGE,

where R1selected from linear or branched (C1-C12) alkyl, (C3-C7) cycloalkyl, phenyl, naphthyl,3C4C5or C8heteroaryl, where one or more heteroatoms, when they are present, regardless of the SEL is Ana from Oh, N, or S, and optionally being substituted, where the substituents are selected from the first group comprising halogen, hydroxy, nitro, cyano, amino, oxo and the oxime, or from a second group including linear or branched (C1-C8)alkyl where the Deputy from the specified second group optionally substituted by R10and where heteroaryl substituted-CH2-S(O)2-tanila;

Y is absent or selected from the group comprising (C1-C8)alkyl-Z, or (C2-C8)alkyl, where Z is selected from sulfur, oxygen or nitrogen;

A and b are independently selected from N, NH, NRe, sulfur, oxygen with the formation of heteroaromatic ring system;

R2, R3and R4independently selected from a first group comprising hydrogen, halogen, or R3and R4in adjacent positions form a phenyl ring;

R5absent or selected from the group comprising-CH2-phenyl, -CH2(CO)R7, -CH2(CO)other8or-CH2(CO)NR8R9that is not necessarily replaced by R10;

R6, R7, R8and R9independently selected from the group including linear or branched (C1-C8)alkyl, (C3-C7)cycloalkyl,5heteroseksualci, benzylpiperidine, phenyl, naphthyl, heteroaryl, alkylether, substituted, or R8and R9education is the comfort piperidine, or R8means 3,4-atlanticcity, where the substituents specified group optionally substituted by R10and heteroaryl means3C4C5or C8heteroaryl, where one or more heteroatoms, when they are present, are independently selected from O, N, or S;

R10selected from halogen, hydroxy, nitro, cyano, amino, oxo, perhalogenated (C1-C6or oxime; and

X is a halide ion;

provided that when the groups/substituents are present in the same or adjacent carbon atoms or nitrogen, together they may not necessarily form a five - or six-, or semiline ring, optionally containing one or more double bonds and optionally containing one or more heteroatoms selected from O, N, or S.

17. The application of article 16, where the specified drug used for the treatment of vascular and neurovascular disorders caused by the accumulation of AGE.

18. The application of article 16, where the specified drug is used to treat kidney disease, nerve damage, retinopathy, immunological disorders, oxidative stress, atherosclerosis, microangiopathy and endothelial dysfunction caused by the accumulation of AGE.

19. The application of article 16, where the specified drug is used for treatment is Alzheimer's disease, restenosis, abnormal obstacles tissue in peritoneal dialysis and erectile dysfunction, caused by the accumulation of AGE.

20. The application of article 16, where the specified drug used for the treatment of inflammatory diseases, discoloration of teeth and dysfunction of other organs caused by accumulation of AGE.

21. A method of treating diseases in mammals, caused by the accumulation of AGE, by the destruction of previously formed the specified AGE of the mammal, comprising introducing an effective amount of the compounds of formula (I) according to claim 1, either by itself or in combination with other medicines for the treatment of diabetes, together with a pharmaceutically acceptable carrier, diluent or excipient.

22. The method according to item 21, where subjected to the treatment of a disease selected from diabetes and age-related vascular and neurovascular disorders.

23. The method according to item 21, where subjected to the treatment of a disease selected from the group including kidney disorders, neurological disorders, atherosclerosis, retinal disease, inflammatory diseases, immunological disorders, oxidative stress, the nonenzymatic Browning in the oral cavity, endothelial dysfunction and dysfunction of other organ and growth impairment.

24. The method according to item 21, where subjected to the treatment of a disease selected from the group including disease al the gamer, restenosis, abnormal obstacle tissue in peritoneal dialysis and erectile dysfunction.

25. The method according to item 21, where the specified connection is selected from a group including:

a) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

b) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(3-phenylmethyl)oxazol-5-yl]pyridinium or its pharmaceutically acceptable salt;

c) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[3-{1-(2-Tien-2'-yl)-2-oxoethylidene-4-thio}methyl-pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

d) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[3-{1-(3,5-dimethylpyrazol-1-yl)methyl}pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

e) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[{3-phenylmethyl}-1-{2-pyridyl} pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

f) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[3{(3,5-dimethylpyrazol-1-yl)methyl-1-pyridyl}pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

g) bromide 1-[2-(cyclopropylamino)-2-oxoethyl]-3-[3-{(3,5-dimethylpyrazol-1-yl)methyl}pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

h) bromide 1-{2-(4-nitro-2-thienyl)-2-oxoethyl}-3-[3-{(3,5-dimethylpyrazol-1-yl)ethyl}pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

i) chloride 1-(2-cyclopropylamino what about the-2-oxoethyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

j) dibromide 3,5-bis-[1-(2-Tien-2'-yl-2-oxoethyl)pyridine-3-yl]pyrazole or its pharmaceutically acceptable salt;

k) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(1-phenyl-3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

l) chloride 1-(2-(5'-methyl-2-thienyl)-2-oxoethyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

m) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[1-phenyl-3-{(3,5-dimethylpyrazol-1-yl)methyl)}pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

n) bromide 1-(2-phenyl-2-oxoethyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

o) chloride 1-(2-cyclopropylamino-2-oxoethyl)-3-[(1-phenyl-3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

R) bromide 1-(2-(4-benzyl-1-piperidinyl)-2-oxoethyl)-3-[(3-phenoxymethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

q) chloride 1-(2-phenyl-2-oxoethyl)-3-[(3-(3,5-dimethylpyrazol-1-yl)methyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

r) chloride 1-(2-(5-methyl-2-thienyl)-2-oxoethyl)-3-[(3-(3,5-dimethylpyrazol-1-yl)methyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

s) chloride 1-(2-phenyl-2-oxoethyl)-3-[(1-phenyl-3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable Sol is;

t) chloride 1-(2-(5-methyl-2-thienyl)-2-oxoethyl)-3-[(3-(2-cyclohexylethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

u) chloride 1-(2-cyclopropylamino-2-oxoethyl)-3-[(3-(2-cyclohexylethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

v) chloride 1-(2-phenyl-2-oxoethyl)-3-[(3-(2-cyclohexylethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

w) chloride 1-(2-cyclopropylamino-2-oxoethyl)-3-[(1-cyclohexyl-3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

x) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(3-phenoxymethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

y) chloride 1-[2-(1-adamantylamine)-2-oxoethyl]-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

z) bromide 1-(2-phenyl-2-oxoethyl)-3-[{3-(3,5-dimethylpyrazol-1-yl)methyl)}-1-phenylpyrazol-5-yl]pyridinium or its pharmaceutically acceptable salt;

AA) bromide 1-(2-(4-nitro-2-thienyl)-2-oxoethyl)-3-[(1-cyclohexyl-3-(3,5-dimethylpyrazol-1-yl)methyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

bb) bromide 1-(2-(4-nitro-2-thienyl)-2-oxoethyl)-3-[(3-(2-cyclohexylethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

cc) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(1-phenyl-3-phenoxymethyl)pyrazole-5-yl]PI is idine or its pharmaceutically acceptable salt;

dd) bromide 1-(2-(4-nitro-2-thienyl)-2-oxoethyl)-3-[(1-phenyl-3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

her) chloride 1-(2-cyclopropylamino-2-oxoethyl)-3-[(3-phenoxymethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

ff) chloride 1-(2-cyclopropylamino-2-oxoethyl)-3-[(1-cyclohexyl-3-(3,5-dimethylpyrazol-1-yl)methyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

gg) bromide 1-(2-(5-chloro-2-thienyl)-2-oxoethyl)-3-[(3-phenoxymethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

hh) chloride 1-(2-phenyl-2-oxoethyl)-3-[(1-phenyl-3-phenoxymethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

ii) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(1-cyclohexyl-3-(3,5-dimethylpyrazol-1-yl)methyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

jj) bromide 1-(2-cyclopropylamino-2-oxoethyl)-3-[(1-phenyl-3-phenoxymethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

kk) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(1-phenyl-3-(2-cyclohexylethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

ll) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(1-cyclohexyl-3-phenoxymethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

mm) of the hydrochloride of 3-[(3-phenylmethyl)pyrazole-5-yl]pyridinyl its pharmaceutically acceptable salt;

nn) of the hydrochloride of 3-[(3-phenoxymethyl)pyrazole-5-yl]pyridine or its pharmaceutically acceptable salt;

OO) 3-[(3,5-dimethylpyrazol-1-yl-methyl)pyrazole-5-yl]pyridine or its pharmaceutically acceptable salt;

PP) 3-[3-(2-cyclohexyl-ethyl)-pyrazole-5-yl]pyridine or its pharmaceutically acceptable salt;

qq) bromide 1-(2-naphthyl-2-oxoethyl)-3-[(3-phenoxymethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

rr) chloride 1-(phenylmethyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

ss) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(3-(1-naphthyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

tt) chloride 1-(2-phenyl-2-oxoethyl)-3-[3-(thienyl-2-yl-methyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

uu) chloride 1-(2-(5-methyl-2-thienyl)-2-oxoethyl)-3-[3-(2-phenylethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

vv) chloride 1-(2-(5-methyl-2-thienyl)-2-oxoethyl)-3-[3-(3-phenoxypropan)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

ww) bromide 1-(isopropyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

XX) chloride 1-(2-(5-methyl-2-thienyl)-2-oxoethyl)-3-[(3-thienylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

yy) chloride 1-(2-the yen-2'-yl-2-oxoethyl)-3-[(3-(N-methyl-indole-3-ylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

zz) bromide 1-(2-naphthyl-2-oxoethyl)-3-[(3-methyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

AAA) chloride 1-(2-(1,4-benzodioxan-6-ylamino-2-oxoethyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

bbb) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(3-phenyl)pyrazole-5-yl]-5-bromopyridine or its pharmaceutically acceptable salt;

CCC) chloride 1-(2-Tien-2'-yl)-2-oxoethyl)-3-[(3-phenyl)pyrazole-5-yl]chinoline or its pharmaceutically acceptable salt and

ddd) 3-[(3-phenyl)pyrazole-5-yl)]quinoline or its pharmaceutically acceptable salt.

26. A method of treating a mammal to inhibit the accumulation by AGE of destruction AGE, which includes an introduction to the needy in the mammal an effective amount of compounds of General formula (I) according to claim 1, either by itself or in combination with other medicines for the treatment of diabetes, together with a pharmaceutically acceptable carrier, diluent or excipient.

27. The method according to p, where the disease being thus treatment selected from renal disorders, neurological disorders, atherosclerosis, retinal disease, inflammatory diseases, immunological disorders, oxidative stress, nonenzymatic Browning in the oral cavity, endothelial dysfunction and dysfunction of others is Gogo body and deterioration of growth.

28. The method according to p, where the disease being thus treatment selected from Alzheimer's disease, restenosis, abnormal obstacles tissue in peritoneal dialysis and erectile dysfunction.

29. The method according to p, where the specified connection is selected from a group including:

a) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

b) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(3-phenylmethyl)oxazol-5-yl]pyridinium or its pharmaceutically acceptable salt;

c) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[3-{1-(2-Tien-2'-yl)-2-oxoethylidene-4-thio}methylpyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

d) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[3-{1-(3,5-dimethylpyrazol-1-yl)methyl}pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

e) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[{3-phenylmethyl}-1-{2-pyridyl} pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

f) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[3-{(3,5-dimethylpyrazol-1-yl)methyl-1-pyridyl}pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

g) bromide 1-[2-(cyclopropylamino)-2-oxoethyl]-3-[3-{(3,5-dimethylpyrazol-1-yl)methyl}pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

h) bromide 1-{2-(4-nitro-2-thienyl)-2-oxoethyl}-3-[3{(3,5-dimethylpyrazol-1-yl)who Thiel}pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

i) chloride 1-(2-cyclopropylamino-2-oxoethyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

j) dibromide 3,5-bis-[1-(2-Tien-2'-yl-2-oxoethyl)-pyridine-3-yl]pyrazole or its pharmaceutically acceptable salt;

k) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(1-phenyl-3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

l) chloride 1-(2-(5'-methyl-2-thienyl)-2-oxoethyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

m) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[1-phenyl, 3-{(3,5-dimethylpyrazol-1-yl)methyl)}pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

n) bromide 1-(2-phenyl-2-oxoethyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

o) chloride 1-(2-cyclopropylamino-2-oxoethyl)-3-[(1-phenyl-3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

R) bromide 1-(2-(4-benzyl-1-piperidinyl)-2-oxoethyl)-3-[(3-phenoxymethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

q) chloride 1-(2-phenyl-2-oxoethyl)-3-[(3-(3,5-dimethylpyrazol-1-yl)methyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

r) chloride 1-(2-(5-methyl-2-thienyl)-2-oxoethyl)-3-[(3-(3,5-dimethylpyrazol-1-yl)methyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable the Yu salt;

s) chloride 1-(2-phenyl-2-oxoethyl)-3-[(1-phenyl-3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

t) chloride 1-(2-(5-methyl-2-thienyl)-2-oxoethyl)-3-[(3-(2-cyclohexylethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

u) chloride 1-(2-cyclopropylamino-2-oxoethyl)-3-[(3-(2-cyclohexylethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

v) chloride 1-(2-phenyl-2-oxoethyl)-3-[(3-(2-cyclohexylethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

w) chloride 1-(2-cyclopropylamino-2-oxoethyl)-3-[(1-cyclohexyl-3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

x) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(3-phenoxymethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

y) chloride 1-[2-(1-adamantylamine)-2-oxoethyl]-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

z) bromide 1-(2-phenyl-2-oxoethyl)-3-[{3-(3,5-dimethylpyrazol-1-yl)methyl)}-1-phenylpyrazol-5-yl]pyridinium or its pharmaceutically acceptable salt;

AA) bromide 1-(2-(4-nitro-2-thienyl)-2-oxoethyl)-3-[(1-cyclohexyl-3-(3,5-dimethylpyrazol-1-yl)methyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

bb) bromide 1-(2-(4-nitro-2-thienyl)-2-oxoethyl)-3[(3-(2-cyclohexylethyl)pyrazole-5-yl]pyridine is or its pharmaceutically acceptable salt;

cc) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(1-phenyl-3-phenoxymethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

dd) bromide 1-(2-(4-nitro-2-thienyl)-2-oxoethyl)-3-[(1-phenyl-3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

her) chloride 1-(2-cyclopropylamino-2-oxoethyl)-3-[(3-phenoxymethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

ff) chloride 1-(2-cyclopropylamino-2-oxoethyl)-3-[(1-cyclohexyl-3-(3,5-dimethylpyrazol-1-yl)methyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

gg) bromide 1-(2-(5-chloro-2-thienyl)-2-oxoethyl)-3-[(3-phenoxymethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

hh) chloride 1-(2-phenyl-2-oxoethyl)-3-[(1-phenyl-3-phenoxymethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

ii) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(1-cyclohexyl-3-(3,5-dimethylpyrazol-1-yl)methyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

jj) bromide 1-(2-cyclopropylamino-2-oxoethyl)-3-[(1-phenyl-3-phenoxymethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

kk) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(1-phenyl-3-(2-cyclohexylethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

ll) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(1-cyclohexyl-3-phenoxy ethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

mm) of the hydrochloride of 3-[(3-phenylmethyl)pyrazole-5-yl]pyridine or its pharmaceutically acceptable salt;

nn) of the hydrochloride of 3-[(3-phenoxymethyl)pyrazole-5-yl] pyridine or its pharmaceutically acceptable salt;

OO) 3-[(3,5-dimethylpyrazol-1-yl-methyl)pyrazole-5-yl]pyridine or its pharmaceutically acceptable salt;

PP) 3-[3-(2-cyclohexylethyl)-pyrazole-5-yl]pyridine or its pharmaceutically acceptable salt;

qq) bromide 1-(2-naphthyl-2-oxoethyl)-3-[(3-phenoxymethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

rr) chloride 1-(phenylmethyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

ss) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(3-(1-naphthyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

tt) chloride 1-(2-phenyl-2-oxoethyl)-3-[3-(thienyl-2-yl-methyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

uu) chloride 1-(2-(5-methyl-2-thienyl)-2-oxoethyl)-3-[3-(2-phenylethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

vv) chloride 1-(2-(5-methyl-2-thienyl)-2-oxoethyl)-3-[3-(3-phenoxypropan)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

ww) bromide 1-(isopropyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

XX) chloride 1-(2-(5-methyl-2-thienyl)-2-oxoethyl)-3-[3-thienylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

yy) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(3-(N-methyl-indole-3-ylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

zz) bromide 1-(2-naphthyl-2-oxoethyl)-3-[(3-methyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

AAA) chloride 1-(2-(1,4-benzodioxan-6-ylamino-2-oxoethyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

bbb) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(3-phenyl)pyrazole-5-yl]-5-bromopyridine or its pharmaceutically acceptable salt;

CCC) chloride 1-(2-Tien-2'-yl)-2-oxoethyl)-3-[(3-phenyl)pyrazole-5-yl]chinoline or its pharmaceutically acceptable salt and

ddd) 3-[(3-phenyl)pyrazole-5-yl)]quinoline or its pharmaceutically acceptable salt.

30. The use of compounds represented by formula (I) or its pharmaceutically acceptable salt

to obtain medicines used for inhibiting the formation of AGE of the mammal,

where R1selected from linear or branched (C1-C12)alkyl, (C3-C7)cycloalkyl, phenyl, naphthyl,3C4C5or C8heteroaryl, where one or more heteroatoms, when they are present, are independently selected from O, N, or S, and optionally substituted, where the substituents are selected from the PE the force, includes halogen, hydroxy, nitro, cyano, amino, oxo and the oxime, or from a second group including linear or branched (C1-C8)alkyl where the Deputy from the specified second group optionally substituted by R10or where heteroaryl substituted-CH2-C(O)-2-tanila;

Y is absent or selected from the group consisting of (C1-C8)alkyl-Z, or (C2-C8)alkyl, where Z is selected from sulfur, oxygen or nitrogen;

A and b are independently selected from N, NH, NR6, sulfur, oxygen with the formation of heteroaromatic ring system;

R2, R3and R4independently selected from a first group comprising hydrogen, halogen, or R3and R4in adjacent positions form a phenyl ring;

R5absent or selected from the group comprising-CH2-phenyl, -CH2(CO)R7, -CH2(CO)other8and-CH2(CO)NR8R9that is not necessarily replaced by R10;

R6, R7, R8and R9independently selected from the group including linear or branched (C1-C8)alkyl, (C3-C7)cycloalkyl, C5heteroseksualci, benzylpiperidine, phenyl, naphthyl, heteroaryl, alkylether, substituted, or R8and R9form a piperidine, or R8means 3,4-atlanticcity, where the substituents indicated the Anna group optionally substituted by R 10and heteroaryl means3C4C5or C8heteroaryl, where one or more heteroatoms, when they are present, are independently selected from O, N, or S;

R10selected from halogen, hydroxy, nitro, cyano, amino, oxo, perhalogenated (C1-C6or oxime; and

X is a halide ion;

provided that, when the groups/substituents are present in the same or adjacent carbon atoms or nitrogen, together they may not necessarily form a five - or six-, or semiline ring, optionally containing one or more double bonds and optionally containing one or more heteroatoms selected from O, N, or S.

31. The application of article 30, where the specified drug used for the treatment and/or prevention of diabetic disorders and age-related diseases associated with the accumulation of AGE.

32. The application of article 30, where the specified drug used for the treatment and/or prevention of vascular and neurovascular disorders caused by the accumulation of AGE.

33. The application of article 30, where the specified drug used for the treatment and/or prevention of kidney disease, nerve damage, retinopathy, immunological disorders, oxidative stress, atherosclerosis, microangiopathy and endothelially the dysfunction, caused by the accumulation of AGE.

34. The application of article 30, where the specified drug used for the treatment and/or prevention of Alzheimer's disease, restenosis, abnormal obstacles tissue in peritoneal dialysis and erectile dysfunction, caused by the accumulation of AGE.

35. The application of article 30, where the specified drug used for the treatment and/or prevention of inflammatory diseases, discoloration of teeth and dysfunction of other organs caused by accumulation of AGE.

36. The application of article 30, where the specified connection used for getting medicines for inhibiting the formation of AGE in a mammal selected from the group including:

a) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

b) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(3-phenylmethyl)oxazol-5-yl]pyridinium or its pharmaceutically acceptable salt;

c) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[3-{1-(2-Tien-2'-yl)-2-oxoethylidene-4-thio}methylpyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

d) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[3-(1-(3,5-dimethylpyrazol-1-yl)methyl}pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

e) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[{3-phenylmethyl}-1-{2-pyridyl}pyrazole-5-yl]pyridinium or headlamp is asepticheski acceptable salt;

f) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[3-{(3,5-dimethylpyrazol-1-yl)methyl-1-pyridyl}pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

g) bromide 1-[2-(cyclopropylamino)-2-oxoethyl]-3-[3-{(3,5-dimethylpyrazol-1-yl)methyl}pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

h) bromide 1-{2-(4-nitro-2-thienyl)-2-oxoethyl}-3-[3-{(3,5-dimethylpyrazol-1-yl)ethyl}pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

i) chloride 1-(2-cyclopropylamino-2-oxoethyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

j) dibromide 3,5-bis-[1-(2-Tien-2'-yl-2-oxoethyl)pyridine-3-yl]pyrazole or its pharmaceutically acceptable salt;

k) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(1-phenyl-3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

l) chloride 1-(2-(5'-methyl-2-thienyl)-2-oxoethyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

m) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[1-phenyl-3-{(3,5-dimethylpyrazol-1-yl)methyl)}pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

n) bromide 1-(2-phenyl-2-oxoethyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

o) chloride 1-(2-cyclopropylamino-2-oxoethyl)-3-[(1-phenyl-3-phenylmethyl)pyrazole-5-yl]pyridinium or Pharma is efticiency acceptable salt;

R) bromide 1-(2-(4-benzyl-1-piperidinyl)-2-oxoethyl)-3-[(3-phenoxymethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

q) chloride 1-(2-phenyl-2-oxoethyl)-3-[(3-(3,5-dimethylpyrazol-1-yl)methyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

r) chloride 1-(2-(5-methyl-2-thienyl)-2-oxoethyl)-3-[(3-(3,5-dimethylpyrazol-1-yl)methyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

s) chloride 1-(2-phenyl-2-oxoethyl)-3-[(1-phenyl-3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

t) chloride 1-(2-(5-methyl-2-thienyl)-2-oxoethyl)-3-[(3-(2-cyclohexylethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

u) chloride 1-(2-cyclopropylamino-2-oxoethyl)-3-[(3-(2-cyclohexylethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

v) chloride 1-(2-phenyl-2-oxoethyl)-3-[(3-(2-cyclohexylethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

w) chloride 1-(2-cyclopropylamino-2-oxoethyl)-3-[(1-cyclohexyl-3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

x) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(3-phenoxymethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

y) chloride 1-[2-(1-adamantylamine)-2-oxoethyl]-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutical is Eski acceptable salt;

z) bromide 1-(2-phenyl-2-oxoethyl)-3-[{3-(3,5-dimethylpyrazol-1-yl)methyl)}-1-phenylpyrazol-5-yl]pyridinium or its pharmaceutically acceptable salt;

AA) bromide 1-(2-(4-nitro-2-thienyl)-2-oxoethyl)-3-[(1-cyclohexyl-3-(3,5-dimethylpyrazol-1-yl)methyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

bb) bromide 1-(2-(4-nitro-2-thienyl)-2-oxoethyl)-3-[(3-(2-cyclohexylethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

cc) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(1-phenyl-3-phenoxymethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

dd) bromide 1-(2-(4-nitro-2-thienyl)-2-oxoethyl)-3-[(1-phenyl-3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

her) chloride 1-(2-cyclopropylamino-2-oxoethyl)-3-[(3-phenoxymethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

ff) chloride 1-(2-cyclopropylamino-2-oxoethyl)-3-[(1-cyclohexyl-3-(3,5-dimethylpyrazol-1-yl)methyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

gg) bromide 1-(2-(5-chloro-2-thienyl)-2-oxoethyl)-3-[(3-phenoxymethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

hh) chloride 1-(2-phenyl-2-oxoethyl)-3-[(1-phenyl-3-phenoxymethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

ii) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(1-cyclohex the l-3-(3,5-dimethylpyrazol-1-yl)methyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

jj) bromide 1-(2-cyclopropylamino-2-oxoethyl)-3-[(1-phenyl-3-phenoxymethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

kk) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(1-phenyl-3-(2-cyclohexylethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

ll) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(1-cyclohexyl-3-phenoxymethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

mm) of the hydrochloride of 3-[(3-phenylmethyl)pyrazole-5-yl]pyridine or its pharmaceutically acceptable salt;

nn) of the hydrochloride of 3-[(3-phenoxymethyl)pyrazole-5-yl]pyridine or its pharmaceutically acceptable salt;

OO) 3-[(3,5-dimethylpyrazol-1-yl-methyl)pyrazole-5-yl]pyridine or its pharmaceutically acceptable salt;

PP) 3-[3-(2-cyclohexylethyl)pyrazole-5-yl]pyridine or its pharmaceutically acceptable salt;

qq) bromide 1-(2-naphthyl-2-oxoethyl)-3-[(3-phenoxymethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

rr) chloride 1-(phenylmethyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

ss) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(3-(1-naphthyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

tt) chloride 1-(2-phenyl-2-oxoethyl)-3-[3-(thienyl-2-yl-methyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

uu) x is arid 1-(2-(5-methyl-2-thienyl)-2-oxoethyl)-3-[3-(2-phenylethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

vv) chloride 1-(2-(5-methyl-2-thienyl)-2-oxoethyl)-3-[3-(3-phenoxypropan)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

ww) bromide 1-(isopropyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

XX) chloride 1-(2-(5-methyl-2-thienyl)-2-oxoethyl)-3-[(3-thienylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

yy) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(3-(N-methyl-indole-3-ylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

zz) bromide 1-(2-naphthyl-2-oxoethyl)-3-[(3-methyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

AAA) chloride 1-(2-(1,4-benzodioxan-6-ylamino-2-oxoethyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

bbb) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(3-phenyl)pyrazole-5-yl]-5-bromopyridine or its pharmaceutically acceptable salt;

CCC) chloride 1-(2-Tien-2'-yl)-2-oxoethyl)-3-[(3-phenyl)pyrazole-5-yl]chinoline or its pharmaceutically acceptable salt and

ddd) 3-[(3-phenyl)pyrazole-5-yl)]quinoline or its pharmaceutically acceptable salt.

37. The method of treatment and/or prevention of diseases caused by the accumulation of AGE in a mammal by inhibiting the formation of AGE at the specified mammal, which comprises introducing an effective amount of the compounds is of formula (I) according to claim 1, either by itself or in combination with other medicines for the treatment of diabetes, together with a pharmaceutically acceptable carrier, diluent or excipient.

38. The method according to clause 37, where the disease under treatment and/or prophylaxis selected from diabetes and age-related vascular and neurovascular disorders.

39. The method according to clause 37, where the disease under treatment and/or prophylaxis selected from Alzheimer's disease, restenosis, abnormal obstacles tissue in peritoneal dialysis and erectile dysfunction.

40. The method according to clause 37, where the disease under treatment and/or prophylaxis selected from renal disorders, neurological disorders, atherosclerosis, retinal diseases, inflammatory diseases, immunological disorders, oxidative stress, nonenzymatic Browning in the oral cavity, endothelial dysfunction or other organs and deteriorating growth.

41. The method according to clause 37 where the specified connection is selected from a group including:

a) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

b) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(3-phenylmethyl)oxazol-5-yl]pyridinium or its pharmaceutically acceptable salt;

c) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[3-{1-(2-Tien-2'-yl)-2-oxoethylidene-4-thio}metalpar the evil-5-yl]pyridinium or its pharmaceutically acceptable salt;

d) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[3-{1-(3,5-dimethylpyrazol-1-yl)methyl}pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

e) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[{3-phenylmethyl}-1-{2-pyridyl} pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

f) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[3-{(3,5-dimethylpyrazol-1-yl)methyl-1-pyridyl}pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

g) bromide 1-[2-(cyclopropylamino)-2-oxoethyl]-3-[3-{(3,5-dimethylpyrazol-1-yl)methyl}pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

h) bromide 1-{2-(4-nitro-2-thienyl)-2-oxoethyl}-3-[3-{(3,5-dimethylpyrazol-1-yl)ethyl}pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

i) chloride 1-(2-cyclopropylamino-2-oxoethyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

j) dibromide 3,5-bis-[1-(2-Tien-2'-yl-2-oxoethyl)pyridine-3-yl]pyrazole or its pharmaceutically acceptable salt;

k) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(1-phenyl-3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

l) chloride 1-(2-(5'-methyl-2-thienyl)-2-oxoethyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

m) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[1-phenyl-3-{(3,5-dimethylpyrazol-1-yl)methyl)}pyrazole-5-yl]pyridi the Oia or its pharmaceutically acceptable salt;

n) bromide 1-(2-phenyl-2-oxoethyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

o) chloride 1-(2-cyclopropylamino-2-oxoethyl)-3-[(1-phenyl-3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

R) bromide 1-(2-(4-benzyl-1-piperidinyl)-2-oxoethyl)-3-[(3-phenoxymethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

q) chloride 1-(2-phenyl-2-oxoethyl)-3-[(3-(3,5-dimethylpyrazol-1-yl)methyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

r) chloride 1-(2-(5-methyl-2-thienyl)-2-oxoethyl)-3-[(3-(3,5-dimethylpyrazol-1-yl)methyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

s) chloride 1-(2-phenyl-2-oxoethyl)-3-[(1-phenyl-3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

t) chloride 1-(2-(5-methyl-2-thienyl)-2-oxoethyl)-3-[(3-(2-cyclohexylethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

u) chloride 1-(2-cyclopropylamino-2-oxoethyl)-3-[(3-(2-cyclohexylethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

v) chloride 1-(2-phenyl-2-oxoethyl)-3-[(3-(2-cyclohexylethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

w) chloride 1-(2-cyclopropylamino-2-oxoethyl)-3-[(1-cyclohexyl-3-phenylmethyl)pyrazole-5-yl]pyridinium or pharmacist who Cesky acceptable salt;

x) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(3-phenoxymethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

y) chloride 1-[2-(1-adamantylamine)-2-oxoethyl]-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

z) bromide 1-(2-phenyl-2-oxoethyl)-3-[{3-(3,5-dimethylpyrazol-1-yl)methyl)}-1-phenylpyrazol-5-yl]pyridinium or its pharmaceutically acceptable salt;

AA) bromide 1-(2-(4-nitro-2-thienyl)-2-oxoethyl)-3-[(1-cyclohexyl-3-(3,5-dimethylpyrazol-1-yl)methyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

bb) bromide 1-(2-(4-nitro-2-thienyl)-2-oxoethyl)-3-[(3-(2-cyclohexylethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

cc) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(1-phenyl-3-phenoxymethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

dd) bromide 1-(2-(4-nitro-2-thienyl)-2-oxoethyl)-3-[(1-phenyl-3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

her) chloride 1-(2-cyclopropylamino-2-oxoethyl)-3-[(3-phenoxymethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

ff) chloride 1-(2-cyclopropylamino-2-oxoethyl)-3-[(1-cyclohexyl-3-(3,5-dimethylpyrazol-1-yl)methyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

gg) bromide 1-(2-(5-chloro-2-thienyl)-2-oxoethyl)-3-[(3-phenoxy ethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

hh) chloride 1-(2-phenyl-2-oxoethyl)-3-[(1-phenyl-3-phenoxymethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

ii) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(1-cyclohexyl-3-(3,5-dimethylpyrazol-1-yl)methyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

jj) bromide 1-(2-cyclopropylamino-2-oxoethyl)-3-[(1-phenyl-3-phenoxymethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

kk) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(1-phenyl-3-(2-cyclohexylethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

ll) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(1-cyclohexyl-3-phenoxymethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

mm) of the hydrochloride of 3-[(3-phenylmethyl)pyrazole-5-yl]pyridine or its pharmaceutically acceptable salt;

nn) of the hydrochloride of 3-[(3-phenoxymethyl)pyrazole-5-yl] pyridine or its pharmaceutically acceptable salt;

OO) 3-[(3,5-dimethylpyrazol-1-yl-methyl)pyrazole-5-yl]pyridine or its pharmaceutically acceptable salt;

PP) 3-[3-(2-cyclohexylethyl)pyrazole-5-yl]pyridine or its pharmaceutically acceptable salt;

qq) bromide 1-(2-naphthyl-2-oxoethyl)-3-[(3-phenoxymethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

rr) chloride 1-(phenylmethyl)-3 [(3-phenylmethyl)pyrazole-5-yl]pyridinium or pharmacist who Cesky acceptable salt;

ss) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(3-(1-naphthyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

tt) chloride 1-(2-phenyl-2-oxoethyl)-3-[3-(thienyl-2-yl-methyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

uu) chloride 1-(2-(5-methyl-2-thienyl)-2-oxoethyl)-3-[3-(2-phenylethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

vv) chloride 1-(2-(5-methyl-2-thienyl)-2-oxoethyl)-3-[3-(3-phenoxy propyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

ww) bromide 1-(isopropyl)-3 [(3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

XX) chloride 1-(2-(5-methyl-2-thienyl)-2-oxoethyl)-3-[(3-thienylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

yy) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(3-(N-methyl-indole-3-ylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

zz) bromide 1-(2-naphthyl-2-oxoethyl)-3-[(3-methyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

AAA) chloride 1-(2-(1,4-benzodioxan-6-ylamino-2-oxoethyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

bbb) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(3-phenyl)pyrazole-5-yl]-5-bromopyridine or its pharmaceutically acceptable salt;

CCC) chloride 1-(2-Tien-2'-yl)-2-oxoethyl)-3-[(3-phenyl)shall irsol-5-yl]chinoline or its pharmaceutically acceptable salt and

ddd) 3-[(3-phenyl)pyrazole-5-yl)]quinoline or its pharmaceutically acceptable salt.

42. The method according to PP, 39 or 40, where the specified connection selected from the group including:

a) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

b) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(3-phenylmethyl)oxazol-5-yl]pyridinium or its pharmaceutically acceptable salt;

c) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[3-{1-(2-Tien-2'-yl)-2-oxoethylidene-4-thio}methylpyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

d) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[3-{1-(3,5-dimethylpyrazol-1-yl)methyl}pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

e) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[{3-phenylmethyl}-1-{2-pyridyl}-pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

f) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[3-{(3,5-dimethylpyrazol-1-yl)methyl-1-pyridyl}pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

g) bromide 1-[2-(cyclopropylamino)-2-oxoethyl]-3-[3-{(3,5-dimethylpyrazol-1-yl)methyl}pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

h) bromide 1-{2-(4-nitro-2-thienyl)-2-oxoethyl}-3-[3-{(3,5-dimethylpyrazol-1-yl)ethyl}pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

i) chloride 1-(2-cyclopropylamino-oxoethyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

j) dibromide 3,5-bis-[1-(2-Tien-2'-yl-2-oxoethyl)pyridine-3-yl]pyrazole or its pharmaceutically acceptable salt;

k) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(1-phenyl-3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

l) chloride 1-(2-(5'-methyl-2-thienyl)-2-oxoethyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

m) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[1-phenyl,3-{(3,5-dimethylpyrazol-1-yl)methyl)}pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

n) bromide 1-(2-phenyl-2-oxoethyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

o) chloride 1-(2-cyclopropylamino-2-oxoethyl)-3-[(1-phenyl-3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

R) bromide 1-(2-(4-benzyl-1-piperidinyl)-2-oxoethyl)-3-[(3-phenoxymethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

q) chloride 1-(2-phenyl-2-oxoethyl)-3-[(3-(3,5-dimethylpyrazol-1-yl)methyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

r) chloride 1-(2-(5-methyl-2-thienyl)-2-oxoethyl)-3-[(3-(3,5-dimethylpyrazol-1-yl)methyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

s) chloride 1-(2-phenyl-2-oxoethyl)-3-[(1-phenyl-3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable Sol is;

t) chloride 1-(2-(5-methyl-2-thienyl)-2-oxoethyl)-3-[(3 (2-cyclohexylethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

u) chloride 1-(2-cyclopropylamino-2-oxoethyl)-3-[(3-(2-cyclohexylethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

v) chloride 1-(2-phenyl-2-oxoethyl)-3-[(3-(2-cyclohexylethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

w) chloride 1-(2-cyclopropylamino-2-oxoethyl)-3-[(1-cyclohexyl-3-phenylmethyl)pyrazol-yl]pyridinium or its pharmaceutically acceptable salt;

x) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(3-phenoxymethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

y) chloride 1-[2-(1-adamantylamine)-2-oxoethyl]-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

z) bromide 1-(2-phenyl-2-oxoethyl)-3-[{3-(3,5-dimethylpyrazol-1-yl)methyl)}-1-phenylpyrazol-5-yl]pyridinium or its pharmaceutically acceptable salt;

AA) bromide 1-(2-(4-nitro-2-thienyl)-2-oxoethyl)-3-[(1-cyclohexyl-3-(3,5-dimethylpyrazol-1-yl)methyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

bb) bromide 1-(2-(4-nitro-2-thienyl)-2-oxoethyl)-3-[(3-(2-cyclohexylethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

cc) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(1-phenyl-3-phenoxymethyl)pyrazole-5-yl]PI is idine or its pharmaceutically acceptable salt;

dd) bromide 1-(2-(4-nitro-2-thienyl)-2-oxoethyl)-3-[(1-phenyl-3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

her) chloride 1-(2-cyclopropylamino-2-oxoethyl)-3-[(3-phenoxymethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

ff) chloride 1-(2-cyclopropylamino-2-oxoethyl)-3-[(1-cyclohexyl-3-(3,5-dimethylpyrazol-1-yl)methyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

gg) bromide 1-(2-(5-chloro-2-thienyl)-2-oxoethyl)-3-[(3-phenoxymethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

hh) chloride 1-(2-phenyl-2-oxoethyl)-3-[(1-phenyl-3-phenoxymethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

ii) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(1-cyclohexyl-3-(3,5-dimethylpyrazol-1-yl)methyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

jj) bromide 1-(2-cyclopropylamino-2-oxoethyl)-3-[(1-phenyl-3-phenoxymethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

kk) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(1-phenyl-3-(2-cyclohexylethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

ll) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(1-cyclohexyl-3-phenoxymethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

mm) of the hydrochloride of 3-[(3-phenylmethyl)pyrazole-5-yl]pyridinyl its pharmaceutically acceptable salt;

nn) of the hydrochloride of 3-[(3-phenoxymethyl)pyrazole-5-yl]pyridine or its pharmaceutically acceptable salt;

OO) 3-[(3,5-dimethylpyrazol-1-yl-methyl)pyrazole-5-yl]pyridine or its pharmaceutically acceptable salt;

PP) 3-[3-(2-cyclohexylethyl)pyrazole-5-yl]pyridine or its pharmaceutically acceptable salt;

qq) bromide 1-(2-naphthyl-2-oxoethyl)-3-[(3-phenoxymethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

rr) chloride 1-(phenylmethyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

ss) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(3-(1-naphthyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

tt) chloride 1-(2-phenyl-2-oxoethyl)-3-[3-(thienyl-2-yl-methyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

uu) chloride 1-(2-(5-methyl-2-thienyl)-2-oxoethyl)-3-[3-(2-phenylethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

vv) chloride 1-(2-(5-methyl-2-thienyl)-2-oxoethyl)-3-[3-(3-phenoxypropan)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

ww) bromide 1-(isopropyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

XX) chloride 1-(2-(5-methyl-2-thienyl)-2-oxoethyl)-3-[(3-thienylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

yy) chloride 1-(2-t the EN-2'-yl-2-oxoethyl)-3-[(3-(N-methyl-indole-3-ylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

zz) bromide 1-(2-naphthyl-2-oxoethyl)-3-[(3-methyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

AAA) chloride 1-(2-(1,4-benzodioxan-6-ylamino-2-oxoethyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

bbb) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(3-phenyl)pyrazole-5-yl]-5-bromopyridine or its pharmaceutically acceptable salt;

CCC) chloride 1-(2-Tien-2'-yl)-2-oxoethyl)-3-[(3-phenyl)pyrazole-5-yl]chinoline or its pharmaceutically acceptable salt and

ddd) 3-[(3-phenyl)pyrazole-5-yl)]quinoline or its pharmaceutically acceptable salt.

43. The use of compounds represented by formula (I) or its pharmaceutically acceptable salt

to get medicines to remove free radicals from the body cells of a mammal,

where R1selected from linear or branched (C1-C12)alkyl, (C3-C7)cycloalkyl, phenyl, naphthyl,3C4C5or C8heteroaryl, where one or more heteroatoms, when they are present, are independently selected from O, N, or S, and optionally substituted, where the substituents are selected from the first group comprising halogen, hydroxy, nitro, cyano, amino, oxo and the oxime, or from the second group, including linear or razvetvlennye is (C 1-C8)alkyl where the Deputy from the specified second group optionally substituted by R10or where heteroaryl substituted-CH2-C(O)-2-tanila;

Y is absent or selected from the group consisting of (C1-C8)alkyl-Z, or (C1-C8)alkyl, where Z is selected from sulfur, oxygen or nitrogen;

A and b are independently selected from N, NH, NR6, sulfur, oxygen with the formation of heteroaromatic ring system;

R2, R3and R4independently selected from a first group comprising hydrogen, halogen, or R3and R4in adjacent positions form a phenyl ring;

R5absent or selected from the group comprising-CH2-phenyl, -CH2(CO)R7, -CH2(CO)other8and-CH2(CO)NR8R9that is not necessarily replaced by R10;

R6, R7, R8and R9independently selected from the group including linear or branched (C1-C8)alkyl, (C3-C7)cycloalkyl, C5heteroseksualci, benzylpiperidine, phenyl, naphthyl, heteroaryl, alkylether, substituted, or R8and R9form a piperidine, or R8means 3,4-atlanticcity, where the substituents specified group optionally substituted by R10and heteroaryl means3With4C5or C8heteroaryl, where the Jn or more heteroatoms, when they are present, are independently selected from O, N, or S;

R10selected from halogen, hydroxy, nitro, cyano, amino, oxo, perhalogenated (C1-C6or oxime; and

X is a halide ion;

provided that, when the groups/substituents are present in the same or adjacent carbon atoms or nitrogen, together they may not necessarily form a five - or six-, or semiline ring, optionally containing one or more double bonds and optionally containing one or more heteroatoms selected from O, N, or S.

44. Use item 43, where the specified drug can be used for the treatment of diseases selected from the group including:

a) neurodegenerative disorders,

b) diabetes and diabetic vascular disorders,

c) intestinal diseases,

d) liver disease,

e) cancer,

f) diseases of the heart,

g) ophthalmic diseases,

h) HIV disease,

(i) diseases of the respiratory tract and

(j) diseases of the kidney.

45. Use item 43, where the specified connection is selected from a group including:

a) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

b) bromide 1-(2-Tien-2'-the l-2-oxoethyl)-3-[(3-phenylmethyl)oxazol-5-yl]pyridinium or its pharmaceutically acceptable salt;

c) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[3-{1-(2-Tien-2'-yl)-2-oxoethyl pyridine-4-thio}methyl-pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

d) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[3-{1-(3,5-dimethylpyrazol-1-yl)methyl} pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

e) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[{3-phenylmethyl}-1-{2-pyridyl}-pyrazole-5-yl]-pyridinium or its pharmaceutically acceptable salt;

f) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[3-{(3,5-dimethylpyrazol-1-yl)methyl-1-pyridyl} pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

g) bromide 1-[2-(cyclopropylamino)-2-oxoethyl]-3-[3-{(3,5-dimethylpyrazol-1-yl)methyl}pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

h) bromide 1-{2-(4-nitro-2-thienyl)-2-oxoethyl}-3-[3-{(3,5-dimethylpyrazol-1-yl)ethyl}pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

i) chloride 1-(2-cyclopropylamino-2-oxoethyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

j) dibromide 3,5-bis-[1-(2-Tien-2'-yl-2-oxoethyl)pyridine-3-yl]pyrazole or its pharmaceutically acceptable salt;

k) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(1-phenyl-3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

l) chloride 1-(2-(5'-methyl-2-thienyl)-2-oxoethyl)-3-[(3-phenylmethyl)pyrazole-yl]pyridinium or its pharmaceutically acceptable salt;

m) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[1-phenyl-3{(3,5-dimethylpyrazol-1-yl)methyl)}pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

n) bromide 1-(2-phenyl-2-oxoethyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

o) chloride 1-(2-cyclopropylamino-2-oxoethyl)-3-[(1-phenyl-3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

R) bromide 1-(2-(4-benzyl-1-piperidinyl)-2-oxoethyl)-3-[(3-phenoxymethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

q) chloride 1-(2-phenyl-2-oxoethyl)-3-[(3-(3,5-dimethylpyrazol-1-yl)methyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

r) chloride 1-(2-(5-methyl-2-thienyl)-2-oxoethyl)-3-[(3-(3,5-dimethylpyrazol-1-yl)methyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

s) chloride 1-(2-phenyl-2-oxoethyl)-3-[(1-phenyl-3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

t) chloride 1-(2-(5-methyl-2-thienyl)-2-oxoethyl)-3-[(3-(2-cyclohexylethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

u) chloride 1-(2-cyclopropylamino-2-oxoethyl)-3-[(3-(2-cyclohexylethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

v) chloride 1-(2-phenyl-2-oxoethyl)-3-[(3-(2-cyclohexylethyl)pyrazole-5-yl]pyridinium or its farmaci is almost acceptable salt;

w) chloride 1-(2-cyclopropylamino-2-oxoethyl)-3-[(1-cyclohexyl-3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

x) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(3-phenoxymethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

y) chloride 1-[2-(1-adamantylamine)-2-oxoethyl]-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

z) bromide 1-(2-phenyl-2-oxoethyl)-3-[{3-(3,5-dimethylpyrazol-1-yl)methyl)}-1-phenylpyrazol-5-yl]pyridinium or its pharmaceutically acceptable salt;

AA) bromide 1-(2-(4-nitro-2-thienyl)-2-oxoethyl)-3-[(1-cyclohexyl-3-(3,5-dimethylpyrazol-1-yl)methyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

bb) bromide 1-(2-(4-nitro-2-thienyl)-2-oxoethyl)-3-[(3-(2-cyclohexylethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

cc) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(1-phenyl-3-phenoxymethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

dd) bromide 1-(2-(4-nitro-2-thienyl)-2-oxoethyl)-3-[(1-phenyl-3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

her) chloride 1-(2-cyclopropylamino-2-oxoethyl)-3-[(3-phenoxymethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

ff) chloride 1-(2-cyclopropylamino-2-oxoethyl)-3-[(1-cyclohexyl-3-(3,5-dimethy the pyrazole-1-yl)methyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

gg) bromide 1-(2-(5-chloro-2-thienyl)-2-oxoethyl)-3-[(3-phenoxymethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

hh) chloride 1-(2-phenyl-2-oxoethyl)-3-[(1-phenyl-3-phenoxymethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

ii) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(1-cyclohexyl-3-(3,5-dimethylpyrazol-1-yl)methyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

jj) bromide 1-(2-cyclopropylamino-2-oxoethyl)-3-[(1-phenyl-3-phenoxymethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

kk) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(1-phenyl-3-(2-cyclohexylethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

ll) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(1-cyclohexyl-3-phenoxymethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

mm) of the hydrochloride of 3-[(3-phenylmethyl)pyrazole-5-yl]pyridine or its pharmaceutically acceptable salt;

nn) of the hydrochloride of 3-[(3-phenoxymethyl)pyrazole-5-yl]pyridine or its pharmaceutically acceptable salt;

OO) 3-[(3,5-dimethylpyrazol-1-yl-methyl)pyrazole-5-yl]pyridine or its pharmaceutically acceptable salt;

PP) 3-[3-(2-cyclohexylethyl)-pyrazole-5-yl]pyridine or its pharmaceutically acceptable salt;

qq) bromide 1-(2-naphthyl-2-oxoethyl)-3-[(3-phenoxymethyl)pyrazole-5-yl]pyridinium is whether its pharmaceutically acceptable salt;

rr) chloride 1-(phenylmethyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

ss) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(3-(1-naphthyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

tt) chloride 1-(2-phenyl-2-oxoethyl)-3-[3-(thienyl-2-yl-methyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

uu) chloride 1-(2-(5-methyl-2-thienyl)-2-oxoethyl)-3-[3-(2-phenylethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

vv) chloride 1-(2-(5-methyl-2-thienyl)-2-oxoethyl)-3-[3-(3-phenoxy propyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

ww) bromide 1-(isopropyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

XX) chloride 1-(2-(5-methyl-2-thienyl)-2-oxoethyl)-3-[(3-thienylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

yy) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(3-(N-methyl-indole-3-ylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

zz) bromide 1-(2-naphthyl-2-oxoethyl)-3-[(3-methyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

AAA) chloride 1-(2-(1,4-benzodioxan-6-ylamino-2-oxoethyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

bbb) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(3-phenyl)pyrazole-5-yl]--bromopyridine or its pharmaceutically acceptable salt;

CCC) chloride 1-(2-Tien-2'-yl)-2-oxoethyl)-3-[(3-phenyl)pyrazole-5-yl]chinoline or its pharmaceutically acceptable salt and

ddd) 3-[(3-phenyl)pyrazole-5-yl)]quinoline or its pharmaceutically acceptable salt.

46. The application of item 44, where the specified connection is selected from a group including:

a) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

b) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(3-phenylmethyl)oxazol-5-yl]pyridinium or its pharmaceutically acceptable salt;

c) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[3-{1-(2-Tien-2'-yl)-2-oxoethyl pyridine-4-thio}methylpyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

d) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[3-{1-(3,5-dimethylpyrazol-1-yl)methyl}pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

e) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[{3-phenylmethyl}-1-{2-pyridyl} pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

f) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[3-{(3,5-dimethylpyrazol-1-yl)methyl-1-pyridyl}pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

g) bromide 1-[2-(cyclopropylamino)-2-oxoethyl]-3-[3-{(3,5-dimethylpyrazol-1-yl)methyl}pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

h) bromide 1-{2-(4-nitro-2-thienyl)-2-oxoethyl}-3-[3-{(3,5-dimethyle the azole-1-yl)ethyl}pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

i) chloride 1-(2-cyclopropylamino-2-oxoethyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

j) dibromide 3,5-bis-[1-(2-Tien-2'-yl-2-oxoethyl)pyridine-3-yl]pyrazole or its pharmaceutically acceptable salt;

k) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(1-phenyl-3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

l) chloride 1-(2-(5'-methyl-2-thienyl)-2-oxoethyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

m) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[1-phenyl-3-{(3,5-dimethylpyrazol-1-yl)methyl)}pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

n) bromide 1-(2-phenyl-2-oxoethyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

o) chloride 1-(2-cyclopropylamino-2-oxoethyl)-3-[(1-phenyl-3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

R) bromide 1-(2-(4-benzyl-1-piperidinyl)-2-oxoethyl)-3-[(3-phenoxymethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

q) chloride 1-(2-phenyl-2-oxoethyl)-3-[(3-(3,5-dimethylpyrazol-1-yl)methyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

r) chloride 1-(2-(5-methyl-2-thienyl)-2-oxoethyl)-3-[(3-(3,5-dimethylpyrazol-1-yl)methyl)pyrazole-5-yl]pyridinium or its pharmaceutically als is salt;

s) chloride 1-(2-phenyl-2-oxoethyl)-3-[(1-phenyl-3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

t) chloride 1-(2-(5-methyl-2-thienyl)-2-oxoethyl)-3-[(3-(2-cyclohexylethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

u) chloride 1-(2-cyclopropylamino-2-oxoethyl)-3-[(3-(2-cyclohexylethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

v) chloride 1-(2-phenyl-2-oxoethyl)-3-[(3-(2-cyclohexylethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

w) chloride 1-(2-cyclopropylamino-2-oxoethyl)-3-[(1-cyclohexyl-3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

x) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(3-phenoxymethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

y) chloride 1-[2-(1-adamantylamine)-2-oxoethyl]-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

z) bromide 1-(2-phenyl-2-oxoethyl)-3-[3-(3,5-dimethylpyrazol-1-yl)methyl)}-1-phenylpyrazol-5-yl]pyridinium or its pharmaceutically acceptable salt;

AA) bromide 1-(2-(4-nitro-2-thienyl)-2-oxoethyl)-3-[(1-cyclohexyl-3-(3,5-dimethylpyrazol-1-yl)methyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

bb) bromide 1-(2-(4-nitro-2-thienyl)-2-oxoethyl)-3-[(3-(2-cyclohexylethyl)pyrazole-5-yl]pyridine is or its pharmaceutically acceptable salt;

cc) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(1-phenyl-3-phenoxymethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

dd) bromide 1-(2-(4-nitro-2-thienyl)-2-oxoethyl)-3-[(1-phenyl-3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

her) chloride 1-(2-cyclopropylamino-2-oxoethyl)-3-[(3-phenoxymethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

ff) chloride 1-(2-cyclopropylamino-2-oxoethyl)-3-[(1-cyclohexyl-3-(3,5-dimethylpyrazol-1-yl)methyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

gg) bromide 1-(2-(5-chloro-2-thienyl)-2-oxoethyl)-3-[(3-phenoxymethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

hh) chloride 1-(2-phenyl-2-oxoethyl)-3-[(1-phenyl-3-phenoxymethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

ii) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(1-cyclohexyl-3-(3,5-dimethylpyrazol-1-yl)methyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

jj) bromide 1-(2-cyclopropylamino-2-oxoethyl)-3-[(1-phenyl-3-phenoxymethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

kk) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(1-phenyl-3-(2-cyclohexylethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

ll) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(1-cyclohexyl-3-phenoxy ethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

mm) of the hydrochloride of 3-[(3-phenylmethyl)pyrazole-5-yl]pyridine or its pharmaceutically acceptable salt;

nn) of the hydrochloride of 3-[(3-phenoxymethyl)pyrazole-5-yl]pyridine or its pharmaceutically acceptable salt;

OO) 3-[(3,5-dimethylpyrazol-1-yl-methyl)pyrazole-5-yl]pyridine or its pharmaceutically acceptable salt;

PP) 3-[3-(2-cyclohexylethyl)-pyrazole-5-yl]pyridine or its pharmaceutically acceptable salt;

qq) bromide 1-(2-naphthyl-2-oxoethyl)-3-[(3-phenoxymethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

rr) chloride 1-(phenylmethyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinyl its pharmaceutically acceptable salt;

ss) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(3-(1-naphthyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

tt) chloride 1-(2-phenyl-2-oxoethyl)-3-[3-(thienyl-2-yl-methyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

uu) chloride 1-(2-(5-methyl-2-thienyl)-2-oxoethyl)-3-[3-(2-phenylethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

vv) chloride 1-(2-(5-methyl-2-thienyl)-2-oxoethyl)-3-[3-(3-phenoxypropan)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

ww) bromide 1-(isopropyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

XX) chloride 1-(2-(5-methyl-2-thienyl)-2-oxoethyl)-3-[(thienylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

yy) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(3-(N-methyl-indole-3-ylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

zz) bromide 1-(2-naphthyl-2-oxoethyl)-3-[(3-methyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

AAA) chloride 1-(2-(1,4-benzodioxan-6-ylamino-2-oxoethyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

bbb) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(3-phenyl)pyrazole-5-yl]-5-bromopyridine or its pharmaceutically acceptable salt;

CCC) chloride 1-(2-Tien-2'-yl)-2-oxoethyl)-3-[(3-phenyl)pyrazole-5-yl]chinoline or its pharmaceutically acceptable salt and

ddd) 3-[(3-phenyl)pyrazole-5-yl)]quinoline or its pharmaceutically acceptable salt.

47. Method of removing free radicals in the cells of the body, including the introduction of a mammal in need in removing free radicals from the cells of his body, the effective amount of the compounds of formula (I), or by itself, or in combination with other antioxidants in a pharmaceutically acceptable carrier, diluent or excipient.

48. The method according to p, where the specified connection is selected from a group including:

a) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

b) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(3-phenylmethyl)oxa the ol-5-yl]pyridinium or its pharmaceutically acceptable salt;

c) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[3-{1-(2-Tien-2'-yl)-2-oxoethylidene-4-thio}methylpyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

d) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[3-{1-(3,5-dimethylpyrazol-1-yl)methyl}pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

e) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[{3-phenylmethyl}-1-{2-pyridyl} pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

f) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[3-{(3,5-dimethylpyrazol-1-yl)methyl-1-pyridyl}pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

g) bromide 1-[2-(cyclopropylamino)-2-oxoethyl]-3-[3-{(3,5-dimethylpyrazol-1-yl)methyl}pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

h) bromide 1-{2-(4-nitro-2-thienyl)-2-oxoethyl}-3-[3-{(3,5-dimethylpyrazol-1-yl)ethyl}pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

i) chloride 1-(2-cyclopropylamino-2-oxoethyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

j) dibromide 3,5-bis-[1-(2-Tien-2'-yl-2-oxoethyl)pyridine-3-yl]pyrazole or its pharmaceutically acceptable salt;

k) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(1-phenyl-3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

l) chloride 1-(2-(5'-methyl-2-thienyl)-2-oxoethyl)-3-[(3-phenylmethyl)pyrazole-5-elpidina or its pharmaceutically acceptable salt;

m) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[1-phenyl-3-{(3,5-dimethylpyrazol-1-yl)methyl)}pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

n) bromide 1-(2-phenyl-2-oxoethyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

o) chloride 1-(2-cyclopropylamino-2-oxoethyl)-3-[(1-phenyl-3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

R) bromide 1-(2-(4-benzyl-1-piperidinyl)-2-oxoethyl)-3-[(3-phenoxymethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

q) chloride 1-(2-phenyl-2-oxoethyl)-3-[(3-(3,5-dimethylpyrazol-1-yl)methyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

r) chloride 1-(2-(5-methyl-2-thienyl)-2-oxoethyl)-3-[(3-(3,5-dimethylpyrazol-1-yl)methyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

s) chloride 1-(2-phenyl-2-oxoethyl)-3-[(1-phenyl-3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

t) chloride 1-(2-(5-methyl-2-thienyl)-2-oxoethyl)-3-[(3-(2-cyclohexylethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

u) chloride 1-(2-cyclopropylamino-2-oxoethyl)-3-[(3-(2-cyclohexylethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

v) chloride 1-(2-phenyl-2-oxoethyl)-3-[(3-(2-cyclohexylethyl)pyrazole-5-yl]pyridinium or its farmaci is almost acceptable salt;

w) chloride 1-(2-cyclopropylamino-2-oxoethyl)-3-[(1-cyclohexyl-3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

x) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(3-phenoxymethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

y) chloride 1-[2-(1-adamantylamine)-2-oxoethyl]-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

z) bromide 1-(2-phenyl-2-oxoethyl)-3-[{3-(3,5-dimethylpyrazol-1-yl)methyl)}-1-phenylpyrazol-5-yl]pyridinium or its pharmaceutically acceptable salt;

AA) bromide 1-(2-(4-nitro-2-thienyl)-2-oxoethyl)-3-[(1-cyclohexyl-3-(3,5-dimethylpyrazol-1-yl)methyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

bb) bromide 1-(2-(4-nitro-2-thienyl)-2-oxoethyl)-3-[(3-(2-cyclohexylethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

cc) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(1-phenyl-3-phenoxymethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

dd) bromide 1-(2-(4-nitro-2-thienyl)-2-oxoethyl)-3-[(1-phenyl-3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

her) chloride 1-(2-cyclopropylamino-2-oxoethyl)-3-[(3-phenoxymethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

ff) chloride 1-(2-cyclopropylamino-2-oxoethyl)-3-[(1-cyclohexyl-3-(3,5-dimethy is)-1-yl)methyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

gg) bromide 1-(2-(5-chloro-2-thienyl)-2-oxoethyl)-3-[(3-phenoxymethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

hh) chloride 1-(2-phenyl-2-oxoethyl)-3-[(1-phenyl-3-phenoxymethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

ii) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(1-cyclohexyl-3-(3,5-dimethylpyrazol-1-yl)methyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

jj) bromide 1-(2-cyclopropylamino-2-oxoethyl)-3-[(1-phenyl-3-phenoxymethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

kk) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(1-phenyl-3-(2-cyclohexylethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

ll) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(1-cyclohexyl-3-phenoxymethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

mm) of the hydrochloride of 3-[(3-phenylmethyl)pyrazole-5-yl]pyridine or its pharmaceutically acceptable salt;

nn) of the hydrochloride of 3-[(3-phenoxymethyl)pyrazole-5-yl]pyridine or its pharmaceutically acceptable salt;

OO) 3-[(3,5-dimethylpyrazol-1-yl-methyl)pyrazole-5-yl]pyridine or its pharmaceutically acceptable salt;

PP) 3-[3-(2-cyclohexylethyl)pyrazole-5-yl]pyridine or its pharmaceutically acceptable salt;

qq) bromide 1-(2-naphthyl-2-oxoethyl)-3-[(3-phenoxymethyl)pyrazole-5-yl]pyridinium is whether its pharmaceutically acceptable salt;

rr) chloride 1-(phenylmethyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

ss) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(3-(1-naphthyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

tt) chloride 1-(2-phenyl-2-oxoethyl)-3-[3-(thienyl-2-yl-methyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

uu) chloride 1-(2-(5-methyl-2-thienyl)-2-oxoethyl)-3-[3-(2-phenylethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

vv) chloride 1-(2-(5-methyl-2-thienyl)-2-oxoethyl)-3-[3-(3-phenoxypropan)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

ww) bromide 1-(isopropyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

XX) chloride 1-(2-(5-methyl-2-thienyl)-2-oxoethyl)-3-[(3-thienylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

yy) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(3-(N-methyl-indole-3-ylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

zz) bromide 1-(2-naphthyl-2-oxoethyl)-3-[(3-methyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

AAA) chloride 1-(2-(1,4-benzodioxan-6-ylamino-2-oxoethyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

bbb) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(3-phenyl)pyrazole-5-yl]-bromopyridine or its pharmaceutically acceptable salt;

CCC) chloride 1-(2-Tien-2'-yl)-2-oxoethyl)-3-[(3-phenyl)pyrazole-5-yl]chinoline or its pharmaceutically acceptable salt and

ddd) 3-[(3-phenyl)pyrazole-5-yl)]quinoline or its pharmaceutically acceptable salt.

49. A method of treating diseases caused by accumulation of free radicals in the body cells of a mammal, comprising the administration to a mammal susceptible to such a disease an effective amount of the compounds of formula (I) according to claim 1.

50. The method according to § 49, where the specified connection is selected from a group including:

a) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

b) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(3-phenylmethyl)oxazol-5-yl]pyridinium or its pharmaceutically acceptable salt;

c) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[3-{1-(2-Tien-2'-yl)-2-oxoethylidene-4-thio}methyl-pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

d) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[3-{1-(3,5-dimethylpyrazol-1-yl)methyl} pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

e) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[{3-phenylmethyl}-1-{2-pyridyl}pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

f) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[3-{(3,5-dimethylpyrazol-1-yl)methyl-1-pyridyl}pyrazole-5-yl]pyridinium or pharmaceutical is acceptable salt;

g) bromide 1-[2-(cyclopropylamino)-2-oxoethyl]-3-[3-{(3,5-dimethylpyrazol-1-yl)methyl}pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

h) bromide 1-{2-(4-nitro-2-thienyl)-2-oxoethyl}-3-[3-{(3,5-dimethylpyrazol-1-yl)ethyl}pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

i) chloride 1-(2-cyclopropylamino-2-oxoethyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

j) dibromide 3,5-bis-[1-(2-Tien-2'-yl-2-oxoethyl)pyridine-3-yl]pyrazole or its pharmaceutically acceptable salt;

k) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(1-phenyl-3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

l) chloride 1-(2-(5'-methyl-2-thienyl)-2-oxoethyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

m) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[1-phenyl-3-{(3,5-dimethylpyrazol-1-yl)methyl)}pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

n) bromide 1-(2-phenyl-2-oxoethyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

o) chloride 1-(2-cyclopropylamino-2-oxoethyl)-3-[(1-phenyl-3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

R) bromide 1-(2-(4-benzyl-1-piperidinyl)-2-oxoethyl)-3-[(3-phenoxymethyl)pyrazole-5-yl]pyridinium or pharmaceutical is acceptable salt;

q) chloride 1-(2-phenyl-2-oxoethyl)-3-[(3-(3,5-dimethylpyrazol-1-yl)methyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

r) chloride 1-(2-(5-methyl-2-thienyl)-2-oxoethyl)-3-[(3-(3,5-dimethylpyrazol-1-yl)methyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

s) chloride 1-(2-phenyl-2-oxoethyl)-3-[(1-phenyl-3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

t) chloride 1-(2-(5-methyl-2-thienyl)-2-oxoethyl)-3-[(3-(2-cyclohexylethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

u) chloride 1-(2-cyclopropylamino-2-oxoethyl)-3-[(3-(2-cyclohexylethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

v) chloride 1-(2-phenyl-2-oxoethyl)-3-[(3-(2-cyclohexylethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

w) chloride 1-(2-cyclopropylamino-2-oxoethyl)-3-[(1-cyclohexyl-3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

x) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(3-phenoxymethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

y) chloride 1-[2-(1-adamantylamine)-2-oxoethyl]-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

z) bromide 1-(2-phenyl-2-oxoethyl)-3-[{3-(3,5-dimethylpyrazol-1-yl)methyl)}-1-phenylpyrazol-5-yl]pyridinium or its formats whitesky acceptable salt;

AA) bromide 1-(2-(4-nitro-2-thienyl)-2-oxoethyl)-3-[(1-cyclohexyl-3-(3,5-dimethylpyrazol-1-yl)methyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

bb) bromide 1-(2-(4-nitro-2-thienyl)-2-oxoethyl)-3-[(3-(2-cyclohexylethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

cc) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(1-phenyl-3-phenoxymethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

dd) bromide 1-(2-(4-nitro-2-thienyl)-2-oxoethyl)-3-[(1-phenyl-3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

her) chloride 1-(2-cyclopropylamino-2-oxoethyl)-3-[(3-phenoxymethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

ff) chloride 1-(2-cyclopropylamino-2-oxoethyl)-3-[(1-cyclohexyl-3-(3,5-dimethyl)-1-yl)methyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

gg) bromide 1-(2-(5-chloro-2-thienyl)-2-oxoethyl)-3-[(3-phenoxymethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

hh) chloride 1-(2-phenyl-2-oxoethyl)-3-[(1-phenyl-3-phenoxymethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

ii) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(1-cyclohexyl-3-(3,5-dimethylpyrazol-1-yl)methyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

jj) bromide 1-(2-cyclopropylamino-2-oxoethyl)-3-[(-phenyl-3-phenoxymethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

kk) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(1-phenyl-3-(2-cyclohexylethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

ll) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(1-cyclohexyl-3-phenoxymethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

mm) of the hydrochloride of 3-[(3-phenylmethyl)pyrazole-5-yl]pyridine or its pharmaceutically acceptable salt;

nn) of the hydrochloride of 3-[(3-phenoxymethyl)pyrazole-5-yl] pyridine or its pharmaceutically acceptable salt;

OO) 3-[(3,5-dimethylpyrazol-1-yl-methyl)pyrazole-5-yl]pyridine or its pharmaceutically acceptable salt;

PP) 3-[3-(2-cyclohexylethyl)-pyrazole-5-yl]pyridine or its pharmaceutically acceptable salt;

qq) bromide 1-(2-naphthyl-2-oxoethyl)-3-[(3-phenoxymethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

rr) chloride 1-(phenylmethyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

ss) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(3-(1-naphthyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

tt) chloride 1-(2-phenyl-2-oxoethyl)-3-[3-(thienyl-2-yl-methyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

uu) chloride 1-(2-(5-methyl-2-thienyl)-2-oxoethyl)-3-[3-(2-phenylethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

vv) chloride 1-(2-(methyl-2-thienyl)-2-oxoethyl)-3-[3-(3-phenoxypropan)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

ww) bromide 1-(isopropyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

XX) chloride 1-(2-(5-methyl-2-thienyl)-2-oxoethyl)-3-[(3-thienylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

yy) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(3-(N-methyl-indole-3-ylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

zz) bromide 1-(2-naphthyl-2-oxoethyl)-3-[(3-methyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

AAA) chloride 1-(2-(1,4-benzodioxan-6-ylamino-2-oxoethyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium or its pharmaceutically acceptable salt;

bbb) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(3-phenyl)pyrazole-5-yl]-5-bromopyridine or its pharmaceutically acceptable salt;

CCC) chloride 1-(2-Tien-2'-yl)-2-oxoethyl)-3-[(3-phenyl)pyrazole-5-yl]chinoline or its pharmaceutically acceptable salt and

ddd) 3-[(3-phenyl)pyrazole-5-yl)]quinoline or its pharmaceutically acceptable salt.

51. The method according to § 49, where the disease is designed to treat selected from the group including:

a) neurodegenerative disorders,

b) diabetes and diabetic vascular disorders,

c) intestinal diseases,

d) liver disease,

e) cancer,

f) diseases of the heart,

g) ophthalmic diseases the project,

h) HIV disease,

(i) diseases of the respiratory tract and

(j) diseases of the kidney.

52. Cosmetic composition for inhibiting the formation and accumulation AGE of destruction AGE or removal of free radicals in mammalian cells, comprising a cosmetically effective amount of the compound represented by formula (I)

or its cosmetically acceptable salt mixed with cosmetically

acceptable diluent, carrier or excipient,

where R1selected from linear or branched (C1-C12)alkyl, (C3-C7)cycloalkyl, phenyl, naphthyl,3C4C5or C8heteroaryl, where one or more heteroatoms, when they are present, are independently selected from O, N, or S, and optionally substituted, where the substituents are selected from the first group comprising halogen, hydroxy, nitro, cyano, amino, oxo and the oxime, or from a second group including linear or branched (C1-C8)alkyl where the Deputy from the specified second group optionally substituted by R10or where heteroaryl substituted-CH2-C(O)-2-tanila;

Y is absent or selected from the group consisting of (C1-C8)alkyl-Z, or (C2-C8)alkyl, where Z is selected from sulfur, oxygen or nitrogen;

A and b are independently selected from N, NH, NR6, sulfur, oxygen with the formation of heteroaromatic ring system;

R2, R3and R4independently selected from a first group comprising hydrogen, halogen, or R3and R4in adjacent positions form a phenyl ring;

R5absent or selected from the group comprising-CH2-phenyl, -CH2(CO)R7, -CH2(CO)other8and-CH2(CO)NR8R9that is not necessarily replaced by R10;

R6, R7, R8and R9independently selected from the group including linear or branched (C1-C8)alkyl, (C3-C7)cycloalkyl,5heteroseksualci, benzylpiperidine, phenyl, naphthyl, heteroaryl, alkylether, substituted, or R8and R9form a piperidine, or R8means 3,4-atlanticcity, where the substituents specified group optionally substituted by R10and heteroaryl means3C4C5or C8heteroaryl, where one or more heteroatoms, when they are present, are independently selected from O, N, or S;

R10selected from halogen, hydroxy, nitro, cyano, amino, oxo, perhalogenated (C1-C6or oxime; and

X is a halide ion;

provided that, when the groups/substituents are present wodnego the same or adjacent carbon atoms or nitrogen, together they may not necessarily form a five - or six-, or semiline ring, optionally containing one or more double bonds and optionally containing one or more heteroatoms selected from O, N, or S.

53. The composition of paragraph 52, for

a) smooth and prevent wrinkles,

b) smoothing and prevent the formation of facial wrinkles,

c) promotion of growth of the epidermis,

d) the sun protection of the skin,

e) recovery and prevention of discoloration of the skin,

f) removing and preventing the formation of age spots,

g) air-conditioning and prevention of dry skin,

h) removal and prevention of traces of suspenders,

i) removal and prevention of skin imperfections,

(j) the care of the skin and keep it healthy

k) the recovery and prevention of senile xerosis,

(l) of the skin and prevent sunburn,

m) the prevention and recovery of loss of collagen,

n) improve skin texture,

a) improvement of skin tone,

p) increasing the thickness of the skin,

q) reduce pore size,

r) restoration of skin luster,

s) minimize signs of fatigue,

t) reduce coal rash,

w the treatment of telangiectasias and

v) to improve the aesthetic appearance of hair and nails.

54. Composition for cosmetic use comprising an effective amount of the compounds with the activity of removing free radicals, destruction AGE and inhibition of AGE, as defined in paragraph 52, or its cosmetically acceptable salts, containing a cosmetically acceptable carrier, where this composition is effective for at least one of the following destinations:

(a) smoothing and preventing the formation of wrinkles,

b) smoothing and preventing the formation of facial wrinkles,

c) promotion of growth of the epidermis,

d) the sun protection of the skin,

e) rehabilitation and prevention of discoloration of the skin,

f) removing and preventing the formation of age spots,

(g) air conditioning and prevention of dry skin,

h) removal and prevention of traces of suspenders,

i) removing and preventing the formation of skin blemishes,

(j) the care of the skin and maintaining its healthy condition,

k) the recovery and prevention of senile xerosis,

l) skin care and prevention of sunburn,

m) the prevention and recovery of loss of collagen,

n) improvement in skin texture,

o) improved skin tone,

is a thicker skin,

q) the reduction of pore size,

r) restoration of skin luster,

s) minimizes signs of fatigue,

t) the decrease in coal-fired rash,

w) the treatment of telangiectasias and

v) improving the aesthetic appearance of hair and nails.

55. The composition according to paragraph 52 or 54 in the form of a solution, gel, ointment, lotion, cream, microemulsion aerosol, dispersion or jelly.

56. The way cosmetic use to repair and prevent the effects of aging and formation of wrinkles on the skin by removing free radicals, comprising applying an effective amount of a cosmetic composition containing the compound of formula (I) according to paragraph 52, or its cosmetically acceptable salts in a cosmetically acceptable medium.

57. The way cosmetic use to repair and prevent the effects of aging and formation of wrinkles on the skin through (a) removal of free radicals; (b) inhibiting the formation of AGE and (C) the destruction of previously formed AGE, including the application of an effective amount of a cosmetic composition, containing the compounds having the activity of removal of free radicals, destructive and AGE AGE inhibitory activity and having the formula (I), as defined in paragraph 52, or its cosmetically acceptable salts in a cosmetically acceptable medium.

58. With the ESP on p or 57, where the effective amount is effective for recovery and prevention of aging.

59. The method according to § 58, where aging is an external aging and/or internal aging.

60. The method according to p, where aging is an external aging.

61. The way cosmetic use according to § 57, where this composition has a restorative and preventive action for at least one of the following:

i) facial wrinkles,

ii) changes in skin color,

iii) age spots,

iv) traces of suspenders,

v) defects of the skin,

vi) senile xerosis and

vii) prevention and recovery loss of collagen.

62. The way cosmetic use to care and preventive actions for dry skin and/or for sunburn, comprising applying an effective amount of a cosmetic composition containing the compound of formula (I), as defined in paragraph 52, or its cosmetically acceptable salts in a cosmetically acceptable medium.

63. The way cosmetic use for growth promotion of the epidermis and/or sunscreen for actions that improve skin texture, improve skin tone, increase skin thickness, reduces the size of pores, restoring the luster of the skin, minimizes the signs of fatigue, vosstanavlivat is the overall tone, attending the telangiectasia, comprising applying an effective amount of a cosmetic composition, containing the compounds having the activity of removal of free radicals, destructive and AGE AGE inhibitory activity and having the formula (I), as defined in paragraph 52, or its cosmetically acceptable salts in a cosmetically acceptable medium.

64. The method according to p, where the specified connection selected from the group comprising the following compounds:

a) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

b) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(5-phenylmethyl)oxazol-3-yl]pyridinium or cosmetically acceptable salt;

c) dibromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[3-{1-(2-Tien-2'-yl)-2-oxoethylidene-4-thio}methyl-pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

d) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[3-{1-(3,5-dimethylpyrazol-1-yl)methyl}pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

e) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[{3-phenylmethyl}-1-{2-pyridyl}pyridyl}pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

f) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[3-{(3,5-dimethylpyrazol-1-yl)methyl-1-pyridyl}pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

g) bromide 1-[2-(cyclopropylamino)-2-oxoethyl]-3-[3-{(3,5-dimethylpyrazol the l-1-yl)methyl}pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

h) bromide 1-2-(4-nitro-2-thienyl)-2-oxoethyl}-3-[3{(3,5-dimethylpyrazol-1-yl)methyl}pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

i) chloride (2-cyclopropylamino-2-oxoethyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

j) dibromide 3,5-bis-[1-(2-Tien-2'-yl-2-oxoethyl)pyridine-3-yl]pyrazole or its cosmetically acceptable salt;

k) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(1-phenyl-3-phenylmethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

l) chloride 1-(2-(5'-methyl-2-thienyl)-2-oxoethyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

m) chloride 1-(2-teen-2'-yl-2-oxoethyl)-3-[1-phenyl-3-{(3,5-dimethylpyrazol-1-yl)methyl)}pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

n) bromide 1-(2-phenyl-2-oxoethyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium and its cosmetically acceptable salt;

o) chloride 1-(2-cyclopropylamino-2-oxoethyl)-3-[1-phenyl-3-phenylmethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

R) bromide 1-(2-(4-benzyl-1-piperidinyl)-2-oxoethyl)-3-[(3-phenoxymethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

q) chloride 1-(2-phenyl-2-oxoethyl)-3-[(3-(3,5-dimethylpyrazol-1-yl)methyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

r) chloride 1-(2-(5-methyl-2-Anil)-2-oxoethyl)-3-[(3-(3,5-dimethylpyrazol-1-yl)methyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

s) chloride 1-(2-phenyl-2-oxoethyl)-3-[(1-phenyl-3-phenylmethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

t) chloride 1-(2-(5-methyl-2-thienyl)-2-oxoethyl)-3-[(3-(2-cyclohexylethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

u) chloride 1-(2-cyclopropylamino-2-oxoethyl)-3-[(3-(2-cyclohexylethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

v) chloride 1-(2-phenyl-2-oxoethyl)-3-[(3-(2-cyclohexylethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

w) chloride 1-(2-cyclopropylamino-2-oxoethyl)-3-[(1"cyclohexyl-3-phenylmethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

x) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(3-phenoxymethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

y) chloride 1-[2-(1-adamantylamine)-2-oxoethyl]-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

z) bromide 1-(2-phenyl-2-oxoethyl)-3-[{3-(3,5-dimethylpyrazol-1-yl)methyl)}-1-phenylpyrazol-5-yl]pyridinium or its cosmetically acceptable salts;

AA) bromide 1-(2-(4-nitro-2-thienyl)-2-oxoethyl)-3-[(1-cyclohexyl-3-(3,5-dimethylpyrazol-1-ylmethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

bb) bromide 1-(2-(4-nitro-2-thienyl)-2-oxoethyl)-3-[(3-(2-cyclohexylethyl)pyrazole-5-yl]pyridinium or its cosmetically priemel the needful salt;

cc) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(1-phenyl-3-phenoxymethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

dd) bromide 1-(2-(4-nitro-2-thienyl)-2-oxoethyl)-3-[(1-phenyl-3-phenylmethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

her) chloride 1-(2-cyclopropylamino-2-oxoethyl)-3-[(3-phenoxymethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

ff) chloride 1-(2-cyclopropylamino-2-oxoethyl)-3-[(1-cyclohexyl-3-(3,5-dimethylpyrazol)methyl)pyrazole-1-yl)methyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

gg) bromide 1-(2-(5-chloro-2-thienyl)-2-oxoethyl)-3-[(3-phenoxymethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

hh) chloride 1-(2-phenyl-2-oxoethyl)-3-[(1-phenyl-3-phenoxymethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

ii) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(1-cyclohexyl-3-(3,5-dimethylpyrazol-1-yl)methyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

jj) bromide 1-(2-cyclopropylamino-2-oxoethyl)-3-[(1-phenyl-3-phenoxymethyl)pyrazole-5-yl]pyridinium and its cosmetically acceptable salts;

kk) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(1-phenyl-3-(2-cyclohexylethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

ll) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(1-cyclohexyl-3-phenoxymethyl)pyrazole-5-elpidina or cosmetically acceptable salt;

mm) of the hydrochloride of 3-[(3-phenylmethyl)pyrazole-5-yl]pyridine or its cosmetically acceptable salt;

nn) of the hydrochloride of 3-[(3-phenoxymethyl)pyrazole-5-yl]pyridine or its cosmetically acceptable salt;

OO) 3-[(3,5-dimethylpyrazol-1-yl-methyl)pyrazole-5-yl]pyridine or its cosmetically acceptable salts;

PP) 3-[3-(2-cyclohexylethyl)pyrazole-5-yl]pyridine or its cosmetically acceptable salts;

qq) bromide 1-(2-naphthyl-2-oxoethyl)-3-[(3-phenoxymethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

rr) chloride 1-(phenylmethyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

ss) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(3-(1-naphthyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

tt) chloride 1-(2-phenyl-2-oxoethyl)-3-[3-(thienyl-2-yl-methyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

uu) chloride 1-(2-(5-methyl-2-thienyl)-2-oxoethyl)-3-[3-(2-phenylethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

vv) chloride 1-(2-(5-methyl-2-thienyl)-2-oxoethyl)-3-[3-(3-phenoxypropan)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

ww) bromide 1-(isopropyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

XX) chloride 1-(2-(5-methyl-2-thienyl)-2-oxoethyl)-3-[(3-thienylmethyl)pyrazole-5-yl]pyridine is or cosmetically acceptable salt;

yy) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(3-(N-methyl-indole-3-ylmethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

zz) bromide 1-(2-naphthyl-2-oxoethyl)-3-[(3-methyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

AAA) chloride 1-(2-(1,4-benzodioxan-6-ylamino-2-oxoethyl)-3-[(3-hexylester)pyrazole-5-yl]pyridinium and / or its cosmetically acceptable salt;

bbb) chloride 1-(2-Tien-2-yl-2-oxoethyl)-3-[(3-phenyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

CCC) chloride 1-(2-Tien-2-yl)-2-oxoethyl)-3-[(3-phenyl)pyrazole-5-yl]chinoline or cosmetically acceptable salt,

ddd) 3-[(3-phenyl)pyrazole-5-yl)]quinoline or its cosmetically acceptable salt.

65. The method according to § 57, where the specified connection selected from the group comprising the following compounds:

a) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

b) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(5-phenylmethyl)oxazol-3-yl]pyridinium or cosmetically acceptable salt;

c) dibromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[3-{1-(2-Tien-2'-yl)-2-oxoethylidene-4-thio}methyl-pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

d) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[3-{1-(3,5-dimethylpyrazol-1-yl)methyl}pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

e) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[{3-phenylmethyl}-1-{2-pyridyl}pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

f) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[3-{(3,5-dimethylpyrazol-1-yl)methyl-1-pyridyl}pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

g) bromide 1-[2-(cyclopropylamino)-2-oxoethyl]-3-[3-{(3,5-dimethylpyrazol-1-yl)methyl}pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

h) bromide 1-{2-(4-nitro-2-thienyl)-2-oxoethyl}-3-[3{(3,5-dimethylpyrazol-1-yl)methyl}pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

i) chloride 1-(2-cyclopropylamino-2-oxoethyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

j) dibromide 3,5-bis-[1-(2-Tien-2'-yl-2-oxoethyl)pyridine-3-yl]pyrazole or its cosmetically acceptable salt;

k) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(1-phenyl-3-phenylmethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

l) chloride 1-(2-(5'-methyl-2-thienyl)-2-oxoethyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

m) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[1-phenyl-3-{(3,5-dimethylpyrazol-1-yl)methyl)}pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

n) bromide 1-(2-phenyl-2-oxoethyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium and its cosmetically acceptable salt;

o) chloride 1-(cyclopropylamino-2-oxoethyl)-3-[(1-phenyl-3-phenylmethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

R) bromide 1-(2-(4-benzyl-1-piperidinyl)-2-oxoethyl)-3-[(3-phenoxymethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

q) chloride 1-(2-phenyl-2-oxoethyl)-3-[(3-(3,5-dimethylpyrazol-1-yl)methyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

r) chloride 1-(2-(5-methyl-2-thienyl)-2-oxoethyl)-3-[(3-(3,5-dimethylpyrazol-1-yl)methyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

s) chloride 1-(2-phenyl-2-oxoethyl)-3-[(1-phenyl-3-phenylmethyl)pyrazole-5-yl]pyridinium and / or its cosmetically acceptable salt;

t) chloride 1-(2-(5-methyl-2-thienyl)-2-oxoethyl)-3-[(3-(2-cyclohexylethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

u) chloride 1-(2-cyclopropylamino-2-oxoethyl)-3-[(3-(2-cyclohexylethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

v) chloride 1-(2-phenyl-2-oxoethyl)-3-[(3-(2-cyclohexylethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

w) chloride 1-(2-cyclopropylamino-2-oxoethyl)-3-[(1-cyclohexyl-3-phenylmethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

x) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(3-phenoxymethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

y) chloride 1-[2-(1-adamantylamine)-2-oxoethyl]-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

AA) bromide 1-(2-(4-nitro-2-thienyl)-2-oxoethyl)-3-[(1-cyclohexyl-3-(3,5-dimethylpyrazol-1-ylmethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

bb) bromide 1-(2-(4-nitro-2-thienyl)-2-oxoethyl)-3-[(3-(2-cyclohexylethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

cc) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(1-phenyl-3-phenoxymethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

dd) bromide 1-(2-(4-nitro-2-thienyl)-2-oxoethyl)-3-[(1-phenyl-3-phenylmethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

her) chloride 1-(2-cyclopropylamino-2-oxoethyl)-3-[(3-phenoxymethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

ff) chloride 1-(2-cyclopropylamino-2-oxoethyl)-3-[(1-cyclohexyl-3-(3,5-dimethylpyrazol)methyl)pyrazole-1-yl)methyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

gg) bromide 1-(2-(5-chloro-2-thienyl)-2-oxoethyl)-3-[(3-phenoxymethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

hh) chloride 1-(2-phenyl-2-oxoethyl)-3-[(1-phenyl-3-phenoxymethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

ii) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(1-cyclohexyl-3-(3,5-dimethylpyrazol-1-yl)shall ethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

jj) bromide 1-(2-cyclopropylamino-2-oxoethyl)-3-[(1-phenyl-3-phenoxymethyl)pyrazole-5-yl]pyridinium and its cosmetically acceptable salts;

kk) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(1-phenyl-3-(2-cyclohexylethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

ll) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(1-cyclohexyl-3-phenoxymethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

mm) of the hydrochloride of 3-[(3-phenylmethyl)pyrazole-5-yl]pyridine or its cosmetically acceptable salt;

nn) of the hydrochloride of 3-[(3-phenoxymethyl)pyrazole-5-yl]pyridine or its cosmetically acceptable salt;

OO) 3-[(3,5-dimethylpyrazol-1-yl-methyl)pyrazole-5-yl]pyridine or its cosmetically acceptable salt;

PP) 3-[3-(2-cyclohexylethyl)pyrazole-5-yl]pyridine or its cosmetically acceptable salts;

qq) bromide 1-(2-naphthyl-2-oxoethyl)-3-[(3-phenoxymethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

rr) chloride 1-(phenylmethyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

ss) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(3-(1-naphthyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

tt) chloride 1-(2-phenyl-2-oxoethyl)-3-[3-(thienyl-2-yl-methyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

uu) chloride 1-(2-(5-methyl-2-thienyl)-2-oxoethyl)-3-[3(2-phenylethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

vv) chloride 1-(2-(5-methyl-2-thienyl)-2-oxoethyl)-3-[3-(3-phenoxypropan)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

ww) bromide 1-(isopropyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

XX) chloride 1-(2-(5-methyl-2-thienyl)-2-oxoethyl)-3-[(3-thienylmethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

yy) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(3-(N-methyl-indole-3-ylmethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

zz) bromide 1-(2-naphthyl-2-oxoethyl)-3-[(3-methyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

AAA) chloride 1-(2-(1,4-benzodioxan-6-ylamino-2-oxoethyl)-3-[(3-hexylester)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

bbb) chloride 1-(2-Tien-2-yl-2-oxoethyl)-3-[(3-phenyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

CCC) chloride 1-(2-Tien-2-yl)-2-oxoethyl)-3-[(3-phenyl)pyrazole-5-yl]chinoline or cosmetically acceptable salt,

ddd) 3-[(3-phenyl)pyrazole-5-yl)]quinoline or its cosmetically acceptable salt.

66. The method according to item 62, where the specified connection selected from the group comprising the following compounds:

a) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

b) bromide 1-(2-Tien-2'-yl-2-octoate is)-3-[(5-phenylmethyl)oxazol-3-yl]pyridinium or cosmetically acceptable salt;

c) dibromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[3-{1-(2-Tien-2'-yl)-2-oxoethylidene-4-thio}methylpyrazole-5-yl]pyridinium or cosmetically acceptable salt;

d) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[3-{1-(3,5-dimethylpyrazol-1-yl)methyl}pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

e) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[{3-phenylmethyl}-1-{2-pyridyl}-pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

f) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[3-{(3,5-dimethylpyrazol-1-yl)methyl-1-pyridyl}pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

g) bromide 1-[2-(cyclopropylamino)-2-oxoethyl]-3-[3-{(3,5-dimethylpyrazol-1-yl)methyl}pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

h) bromide 1-{2-(4-nitro-2-thienyl)-2-oxoethyl}-3-[3-{(3,5-dimethylpyrazol-1-yl)methyl}pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

i) chloride 1-(2-cyclopropylamino-2-oxoethyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

j) dibromide 3,5-bis-[1-(2-Tien-2'-yl-2-oxoethyl)pyridine-3-yl]pyrazole or its cosmetically acceptable salt;

k) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(1-phenyl-3-phenylmethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

l) chloride 1-(2-(5'-methyl-2-thienyl)-2-oxoethyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium or cosmetics / products the Eski acceptable salt;

m) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[1-phenyl-3-{(3,5-dimethylpyrazol-1-yl)methyl)}pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

n) bromide 1-(2-phenyl-2-oxoethyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium and its cosmetically acceptable salt;

o) chloride 1-(2-cyclopropylamino-2-oxoethyl)-3-[(1-phenyl-3-phenylmethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

R) bromide 1-(2-(4-benzyl-1-piperidinyl)-2-oxoethyl)-3-[(3-phenoxymethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

q) chloride 1-(2-phenyl-2-oxoethyl)-3-[(3-(3,5-dimethylpyrazol-1-yl)methyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

r) chloride 1-(2-(5-methyl-2-thienyl)-2-oxoethyl)-3-[(3-(3,5-dimethylpyrazol-1-yl)methyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

s) chloride 1-(2-phenyl-2-oxoethyl)-3-[(1-phenyl-3-phenylmethyl)pyrazole-5-yl]pyridinium and / or its cosmetically acceptable salt;

t) chloride 1-(2-(5-methyl-2-thienyl)-2-oxoethyl)-3-[(3-(2-cyclohexylethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

u) chloride 1-(2-cyclopropylamino-2-oxoethyl)-3-[(3-(2-cyclohexylethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

v) chloride 1-(2-phenyl-2-oxoethyl)-3-[(3-(2-cyclohexylethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

w) chloride 1-(2-cyclopropylamino-2-oxoethyl)-3-[(1-cyclohexyl-3-phenylmethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

x) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(3-phenoxymethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

y) chloride 1-[2-(1-adamantylamine)-2-oxoethyl]-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

z) bromide 1-(2-phenyl-2-oxoethyl)-3-[3-(3,5-dimethylpyrazol-1-yl)methyl)}-1-phenylpyrazol-5-yl]pyridinium or cosmetically acceptable salt;

AA) bromide 1-(2-(4-nitro-2-thienyl)-2-oxoethyl)-3-[(1-cyclohexyl-3-(3,5-dimethylpyrazol-1-yl)-methyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

bb) bromide 1-(2-(4-nitro-2-thienyl)-2-oxoethyl)-3-[(3-(2-cyclohexylethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

cc) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(1-phenyl-3-phenoxymethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

dd) bromide 1-(2-(4-nitro-2-thienyl)-2-oxoethyl)-3-[(1-phenyl-3-phenylmethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

her) chloride 1-(2-cyclopropylamino-2-oxoethyl)-3-[(3-phenoxymethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

ff) chloride 1-(2-cyclopropylamino-2-oxoethyl)-3-[(1-cyclohexyl-3-(3,5-dimethylpyrazol)methyl)pyrazole-1-yl)methyl)piraso the-5-yl]pyridinium or cosmetically acceptable salt;

gg) bromide 1-(2-(5-chloro-2-thienyl)-2-oxoethyl)-3-[(3-phenoxymethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

hh) chloride 1-(2-phenyl-2-oxoethyl)-3-[(1-phenyl-3-phenoxymethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

ii) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(1-cyclohexyl-3-(3,5-dimethylpyrazol-1-yl)methyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

jj) bromide 1-(2-cyclopropylamino-2-oxoethyl)-3-[(1-phenyl-3-phenoxymethyl)pyrazole-5-yl]pyridinium and its cosmetically acceptable salts;

kk) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(1-phenyl-3-(2-cyclohexylethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

ll) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(1-cyclohexyl-3-phenoxymethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

mm) of the hydrochloride of 3-[(3-phenylmethyl)pyrazole-5-yl]pyridine or its cosmetically acceptable salt;

nn) of the hydrochloride of 3-[(3-phenoxymethyl)pyrazole-5-yl] pyridine or its cosmetically acceptable salt;

OO) 3-[(3,5-dimethylpyrazol-1-yl-methyl)pyrazole-5-yl]pyridine or its cosmetically acceptable salt;

PP) 3-[3-(2-cyclohexylethyl)pyrazole-5-yl]pyridine or its cosmetically acceptable salts;

qq) bromide 1-(2-naphthyl-2-oxoethyl)-3-[(3-phenoxymethyl)pyrazole-5-yl]pyridinium or its cosmetically acceptable with the ü;

rr) chloride 1-(phenylmethyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

ss) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(3-(1-naphthyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

tt) chloride 1-(2-phenyl-2-oxoethyl)-3-[3-(thienyl-2-ylmethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

uu) chloride 1-(2-(5-methyl-2-thienyl)-2-oxoethyl)-3-[3-(2-phenylethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

vv) chloride 1-(2-(5-methyl-2-thienyl)-2-oxoethyl)-3-[3-(3-phenoxypropan)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

ww) bromide 1-(isopropyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

XX) chloride 1-(2-(5-methyl-2-thienyl)-2-oxoethyl)-3-[(3-thienylmethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

yy) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(3-(N-methyl-indole-3-ylmethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

zz) bromide 1-(2-naphthyl-2-oxoethyl)-3-[(3-methyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

AAA) chloride 1-(2-(1,4-benzodioxan-6-ylamino-2-oxoethyl)-3-[(3-hexylester)pyrazole-5-yl]pyridinium and / or its cosmetically acceptable salt;

bbb) chloride 1-(2-Tien-2-yl-2-oxoethyl)-3-[(3-phenyl)pyrazole-5-yl]pyridinium or its cosmetically ramlau salt;

CCC) chloride 1-(2-Tien-2-yl)-2-oxoethyl)-3-[(3-phenyl)pyrazole-5-yl]chinoline or cosmetically acceptable salt,

ddd) 3-[(3-phenyl)pyrazole-5-yl)]quinoline or its cosmetically acceptable salt.

67. The method according to p, where the specified connection selected from the group comprising the following compounds:

a) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

b) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(5-phenylmethyl)oxazol-3-yl]pyridinium or cosmetically acceptable salt;

c) dibromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[3-{1-(2-Tien-2'-yl)-2-oxoethyl]pyridine-4-thio}methylpyrazole-5-yl]pyridinium or cosmetically acceptable salt;

d) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[3-{1-(3,5-dimethylpyrazol-1-yl)methyl}pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

e) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[{3-phenylmethyl}-1-{2-pyridyl}pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

f) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[3-{(3,5-dimethylpyrazol-1-yl)methyl-1-pyridyl}pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

g) bromide 1-[2-(cyclopropylamino)-2-oxoethyl]-3-[3-{(3,5-dimethylpyrazol-1-yl)methyl}pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

h) bromide 1-{2-(4-nitro-2-thienyl)-2-oxoethyl}-3-[3-{(3,5-dimethylpyrazol-1-yl)m is Teal}pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

i) chloride 1-(2-cyclopropylamino-2-oxoethyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

j) dibromide 3,5-bis-[1-(2-Tien-2'-yl-2-oxoethyl)pyridine-3-yl]pyrazole or its cosmetically acceptable salt;

k) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(1-phenyl-3-phenylmethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

l) chloride 1-(2-(5'-methyl-2-thienyl)-2-oxoethyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

m) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[1-phenyl-3-{(3,5-dimethylpyrazol-1-yl)methyl)}pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

n) bromide 1-(2-phenyl-2-oxoethyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium and its cosmetically acceptable salt;

o) chloride 1-(2-cyclopropylamino-2-oxoethyl)-3-[(1-phenyl-C-phenylmethyl)pyrazole - 5-yl]pyridinium or cosmetically acceptable salt;

R) bromide 1-(2-(4-benzyl-1-piperidinyl)-2-oxoethyl)-3-[(3-phenoxymethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

q) chloride 1-(2-phenyl-2-oxoethyl)-3-[(3-(3,5-dimethylpyrazol-1-yl)methyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

r) chloride 1-(2-(5-methyl-2-thienyl)-2-oxoethyl)-3-[(3-(3,5-dimethylpyrazol-1-yl)methyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

s) chloride 1-(2-FeNi is-2-oxoethyl)-3-[(1-phenyl-3-phenylmethyl)pyrazole-5-yl]pyridinium and / or its cosmetically acceptable salt;

t) chloride 1-(2-(5-methyl-2-thienyl)-2-oxoethyl)-3-[(3-(2-cyclohexylethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

u) chloride 1-(2-cyclopropylamino-2-oxoethyl)-3-[(3-(2-cyclohexylethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

v) chloride 1-(2-phenyl-2-oxoethyl)-3-[(3-(2-cyclohexylethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

w) chloride 1-(2-cyclopropylamino-2-oxoethyl)-3-[(1-cyclohexyl-3-phenylmethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

x) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(3-phenoxymethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

y) chloride 1-[2-(1-adamantylamine)-2-oxoethyl]-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

z) bromide 1-(2-phenyl-2-oxoethyl)-3-[{3-(3,5-dimethylpyrazol-1-yl)methyl)} 1-phenyl-pyrazole-5-yl]pyridinium or its cosmetically acceptable salts;

AA) bromide 1-(2-(4-nitro-2-thienyl)-2-oxoethyl)-3-[(1-cyclohexyl-3-(3,5-dimethylpyrazol-1-yl-methyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

bb) bromide 1-(2-(4-nitro-2-thienyl)-2-oxoethyl)-3-[(3-(2-cyclohexylethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

cc) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(1-phenyl-3-phenoxymethyl)pyrazole-5-yl]pyridinium or cosmeticsmile.info salt;

dd) bromide 1-(2-(4-nitro-2-thienyl)-2-oxoethyl)-3-[(1-phenyl-3-phenylmethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

her) chloride 1-(2-cyclopropylamino-2-oxoethyl)-3-[(3-phenoxymethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

ff) chloride 1-(2-cyclopropylamino-2-oxoethyl)-3-[(1-cyclohexyl-3-(3,5-dimethylpyrazol)methyl)pyrazole-1-yl)methyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

gg) bromide 1-(2-(5-chloro-2-thienyl)-2-oxoethyl)-3-[(3-phenoxymethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

hh) chloride 1-(2-phenyl-2-oxoethyl)-3-[(1-phenyl-3-phenoxymethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

ii) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(1-cyclohexyl-3-(3,5-dimethylpyrazol-1-yl)methyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

jj) bromide 1-(2-cyclopropylamino-2-oxoethyl)-3-[(1-phenyl-3-phenoxymethyl)pyrazole-5-yl]pyridinium and its cosmetically acceptable salts;

kk) bromide 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(1-phenyl-3-(2-cyclohexylethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

ll) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(1-cyclohexyl-3-phenoxymethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

mm) of the hydrochloride of 3-[(3-phenylmethyl)pyrazole-5-yl]pyridine or its bottle : the ski acceptable salt;

nn) of the hydrochloride of 3-[(3-phenoxymethyl)pyrazole-5-yl] pyridine or its cosmetically acceptable salt;

OO) 3-[(3,5-dimethylpyrazol-1-yl-methyl)pyrazole-5-yl]pyridine or its cosmetically acceptable salt;

PP) 3-[3-(2-cyclohexylethyl)-pyrazole-5-yl]pyridine or its cosmetically acceptable salts;

qq) bromide 1-(2-naphthyl-2-oxoethyl)-3-[(3-phenoxymethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

rr) chloride 1-(phenylmethyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

ss) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(3-(1-naphthyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

tt) chloride 1-(2-phenyl-2-oxoethyl)-3-[3-(thienyl-2-yl-methyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

uu) chloride 1-(2-(5-methyl-2-thienyl)-2-oxoethyl)-3-[3-(2-phenylethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

vv) chloride 1-(2-(5-methyl-2-thienyl)-2-oxoethyl)-3-[3-(3-phenoxypropan)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

ww) bromide 1-(isopropyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

XX) chloride 1-(2-(5-methyl-2-thienyl)-2-oxoethyl)-3-[(3-thienylmethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

yy) chloride 1-(2-Tien-2'-yl-2-oxoethyl)-3-[(3-(N-methyl-Indo-Christ.-3-ylmethyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

zz) bromide 1-(2-naphthyl-2-oxoethyl)-3-[(3-methyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

AAA) chloride 1-(2-(1,4-benzodioxan-6-ylamino-2-oxoethyl)-3-[(3-phenylmethyl)pyrazole-5-yl]pyridinium and / or its cosmetically acceptable salt;

bbb) chloride 1-(2-Tien-2-yl-2-oxoethyl)-3-[(3-phenyl)pyrazole-5-yl]pyridinium or cosmetically acceptable salt;

CCC) chloride 1-(2-Pien-2-yl)-2-oxoethyl)-3-[(3-phenyl)pyrazole-5-yl]chinoline or cosmetically acceptable salt,

ddd) 3-[(3-phenyl)pyrazole-5-yl)]quinoline or its cosmetically acceptable salt.

68. Cosmetic composition according to paragraph 52, where the concentration of the indicated compound is 0.005 to 50% by weight.

69. Cosmetic composition according p, where the preferred concentration of the indicated compound is from 0.25 to 5.0% by weight.

70. Cosmetic composition comprising a compound of formula (I), as defined in paragraph 52, or other cosmetically acceptable salts, and one or more agents selected from the group consisting of softening agents, emulsifiers, agents, modifying the differentiation and/or proliferation and/or pigmentation, antiparasitics agents, preservatives, alcohols, perfumes and fragrances, thickeners, humectants, dyes, silicones, exfoliating agents, keratolytic agents, retinoids, sunscreen is hentov, amplifiers permeability of the skin, anti-inflammatory agents, vitamins, thrombolytic agents, antikoaguliruyuschee agents, capillary protective equipment, additional antioxidants, hormones, antibacterial agents, antiviral agents, steroidal anti-inflammatory agents, anesthetics, protivoseborainey agents, agents dandruff agents against acne, agents against free radicals, analgesics, lipophilic compounds, antihistamine agents, repellents against insects, cooling the skin compounds, lubricating agents, and antifungal agents, and mixtures thereof.

71. The way cosmetic use, including the application of an effective amount of a composition as defined in item 70.

72. The method of peritoneal dialysis diabetic patient where one or more compounds according to claim 1 is injected with a fluid for dialysis used in the dialysis process.

73. The use of compounds according to claim 1 for receiving fluid for dialysis used in a peritoneal dialysis patient diabetic.



 

Same patents:

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to compounds of the formula (1):

and their salts wherein ring A comprises optionally heteroatom oxygen (O); dotted lines represent the optional unsaturation; R1 represents (C1-C4)-alkoxy-group; R2 and R3 represent independently hydrogen atom (H), optionally halogenated (C1-C4)-alkyl, optionally substituted aromatic group, or R2 and R3 in common can form substituted or unsubstituted 5-7-membered ring condensed with ring E; k = 0-4; L1 represents a covalent bond or (C1-C6)-alkyl optionally comprising nitrogen atom (N); X represents unsubstituted or substituted carbon © atom or N, or represents O or sulfur (S) atom; Ar represents phenylene; each n = 0-2 independently; each R represents independently H or (C1-C6)-alkyl; Y represents optionally substituted aromatic or heteroaromatic group or 5-11-membered heterocyclic group comprising 1-4 heteroatoms cgosen from N, O and S that are bound with chemokine receptors comprising CXCR4 and CCR5, and elicit the protective affect against damage of host-cells by human immunodeficiency virus (HIV).

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.

FIELD: organic chemistry, chemical technology, medicine, pharmacy.

SUBSTANCE: invention describes novel derivatives of N-triazolylmethylpiperazine of the general formula (I): , wherein R1 means hydrogen atom or (lower)-alkyl; R2 means (lower)-alkyl, di-(lower)-alkylamino-(lower)-alkyl, (lower)-alkoxycarbonyl-(lower)-alkyl, cycloalkyl with 5-6 carbon atoms in cycle, pyridinyl-(lower)-alkyl, possibly bi-substituted phenyl-(lower)-alkyl, phenyloxy-(lower)-alkyl substituted with halogen atom in phenyl ring; R3 means (lower)-alkyl, (lower)-alkyloxycarbonyl-(lower)-alkyl or (C5-C6)-cycloalkyl, or both R2 and R3 in common with nitrogen atom to which they are bound form substituted pyrrolidine ring or cyclic group of the formula (a): , wherein A means nitrogen, oxygen atom, methylene or methylidene group wherein its double bond is formed in common with adjacent carbon atom at position 3 of the group (a), and if A means nitrogen atom then this nitrogen atom has substitute R4', and in this case n means 2 or 3, and R4' means (lower)-alkyl, possibly substituted phenyl-(lower)-alkyl, possibly substituted pyridyl, pyridyl-(lower)-alkyl, (lower)-alkoxycarbonyl-(lower)-alkyl, pyrimidyl-(C5-C6)-cycloalkyl, (C5-C6)-cycloalkyl-(lower)-alkyl or morpholinyl-(lower)-alkyl; R4 and R5 mean hydrogen atom and in all cases n means a whole number from 1 to 2; R4 means hydrogen atom, (lower)-alkyl, (lower)-alkoxy-(lower)-alkyl, (lower)-alkoxycarbonyl, (lower)-alkoxycarbonyl-(lower)-alkyl, di-(lower)-alkylamino-(lower)-alkyl, phenyl, pyrrolidinyl, pyrrolidinyl-(lower)-alkyl, pyridyl or piperidinyl, cyclohexyl, cyclohexyl-(lower)-alkyl, phenyl-(lower)-alkyl, pyridyl monosubstituted with (lower)-alkyl, phenyl-(lower)-alkyl monosubstituted with (lower)-alkyl, pyrimidyl, pyridyl-(lower)-alkyl, morpholinyl-(lower)-alkyl; R5 means hydrogen atom, (lower)-alkyl or (lower)-alkoxy-(lower)-alkyl, or R4 and R5 taken in common mean spiroethylenedioxy-group bound with carbon atom of the group (a), (C3-C4)-alkylene bound with two adjacent atoms of the group (a) or phenyl anellated by two adjacent carbon atoms of the group (a), and their physiologically acceptable acid-additive salts also. Also, invention relates to methods for synthesis of these compounds, a medicinal agent based on thereof and intermediate compound in synthesis of novel compounds. Novel compounds are antagonists of neurokinin receptors and display effect in peripheral region preferably and can be used in treatment of functional and inflammatory disorders of digestive tract.

EFFECT: improved preparing method, valuable medicinal properties of derivatives.

10 cl, 4 tbl, 4 ex

FIELD: organic chemistry.

SUBSTANCE: invention relates to new benzofuran derivatives of formula 1 , wherein X represents group of formula -N= or -CH=; Y represents optionally substituted amino group, optionally substituted cycloalkyl group, or optionally substituted saturated heterocycle; A represents direct bond, carbon chain optionally containing double bond in molecular or in the end(s) thereof, or oxygen atom; R1 represents hydrogen, halogen, lower alkoxy, cyano, or amino optionally substituted with lower alkyl B represents optionally substituted benzene ring of formula ; and R2 represents hydrogen or lower alkyl; or pharmaceutically acceptable salt thereof. Invention also relates to pharmaceutical composition containing abovementioned compounds, uses thereof and method for thrombosis treatment.

EFFECT: new compounds for thrombosis treatment.

27 cl, 2 tbl, 429 ex

FIELD: organic chemistry, chemical technology, medicine, pharmacy.

SUBSTANCE: invention relates to compounds of the formula (I)

or their pharmaceutically acceptable salts or esters hydrolyzing in vivo and possessing activity inhibiting the cellular cycle and selective with respect to CDK-2, CDK-4 and CDK-6. Compounds can be used in cancer treatment. In the formula (I) R1 represents halogen atom, amino-group, (C1-C)-alkyl, (C1-C6)-alkoxy-group; p = 0-4 wherein values R1 can be similar or different; R2 represents sulfamoyl or group Ra-Rb-; q = 0-2 wherein values R2 can be similar or different and wherein p + q = 0-5; R3 represents halogen atom or cyano-group; n = 0-2 wherein values R3 can be similar or different; R4 represents hydrogen atom, (C1-C6)-alkyl, (C2-C6)-alkenyl, (C2-C6)-alkynyl, (C3-C8)-cycloalkyl, phenyl or heterocyclic group bound with carbon atom wherein R4 can be optionally substituted at carbon atom with one or some groups Rd; R5 and R6 are chosen independently from hydrogen, halogen atom, (C1-C)-alkyl, (C2-C6)-alkenyl or (C3-C8)-cycloalkyl wherein R5 and R6 can be substituted at carbon atom independently of one another with one or some groups Re; Ra is chosen from (C1-C6)-alkyl, (C2-C6)-alkenyl, (C2-C6)-alkynyl, (C3-C8)-cycloalkyl, (C3-C8)-cycloalkyl-(C1-C6)-alkyl, phenyl, heterocyclic group, phenyl-(C1-C)-alkyl or (heterocyclic group)-(C1-C6)-alkyl wherein Ra can be substituted optionally at carbon atom with one or some groups Rg and wherein if indicated heterocyclic group comprises residue -NH- then its nitrogen atom can be optionally substituted with group chosen from the group Rh; Rb represents -N(Rm)C(O)-, -C(O)N(Rm)-, -S(O)r-, -OC(O)N(Rm)SO2-, -SO2N(Rm)- or -N(Rm)SO2- wherein Rm represents hydrogen atom or (C1-C6)-alkyl, and r = 1-2. Also, invention relates to methods for synthesis of these compounds, a pharmaceutical composition, method for inhibition and using these compounds.

EFFECT: improved preparing method, valuable medicinal properties of compounds and pharmaceutical compositions.

24 cl, 3 sch, 166 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to derivatives of amide of the general formula (I)

wherein X means -CH; Y means -CH or nitrogen atom (N); m = 1 or 2; R1 means (C1-C6)-alkyl, (C1-C)-alkoxy-group, N,N-di-[(C1-C6)-alkyl]-amino-group, heterocyclyl-(C1-C6)-alkyl wherein heterocyclyl represents piperazinyl or homopiperazinyl; n = 3; R2 means halogen atom, (C1-C6)-alkyl; R3 means hydrogen atom; Q means phenyl optionally substituted with cyano-group, or pyridyl optionally substituted with morpholino-group, or their pharmaceutically acceptable salts, to methods for synthesis of indicated compounds, pharmaceutical compositions containing thereof and their using in treatment of diseases or states mediated by cytokines.

EFFECT: improved preparing methods, valuable medicinal properties of compounds and pharmaceutical compositions.

10 cl, 2 tbl, 7 ex

FIELD: organic chemistry, agriculture.

SUBSTANCE: invention relates to anthranylamide derivative selected from compound of formula I or N-oxides thereof, wherein R1 represents methyl, F, Cl, Br; R2 represents F, Cl, Br, I, CF3; R3 represents CF3, Cl, Br, OCH2CF3; R4a represents C1-C4-alkyl; R4b represents H, CH3; and R5 represents Cl, Br, and agriculturally acceptable salt thereof. Also disclosed are composition for pest controlling containing biologically effective amount of formula I and at least one additional component selected from group comprising surfactants, solid and liquid diluents; composition for invertebrate insect controlling containing biologically effective amount of formula I and at least one additional biologically active compound or agent. Also disclosed are method for insect controlling as well as intermediates such as benzoxazinone and parasolocarboxylic acid derivatives.

EFFECT: compounds with insecticide activity, useful in insect controlling.

20 cl, 16 tbl, 33 ex

FIELD: organic chemical, pharmaceuticals.

SUBSTANCE: invention relates to new compounds having JAK3 kinase inhibitor activity, methods for production thereof, intermediates, and pharmaceutical composition containing the same. In particular disclosed are aromatic 6,7-disubstituted 3-quinolinecarboxamide derivatives of formula I and pharmaceutically acceptable salts thereof useful in production of drugs for treatment of diseases mediated with JAK3. In formula n = 0 or 1; X represents NR3 or O; Ar is selected from phenyl, tetrahydronaphthenyl, indolyl, pyrasolyl, dihydroindenyl, 1-oxo-2,3-dihydroindenyl or indasolyl, wherein each residue may be substituted with one or more groups selected from halogen, hydroxy, cyano, C1-C8-alkoxy, CO2R8, CONR9R10 C1-C8-alkyl-O-C1-C8-alkyl, etc., wherein R-groups are independently hydrogen atom or C1-C8-alkyl; meanings of other substitutes are as define in description.

EFFECT: new compounds having value biological properties.

17 cl, 222 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, herbicides, agriculture.

SUBSTANCE: invention describes using 2-morpholyl-6-piperidyl-4-[(4'-(ethoxycarbonyl-5'-1',2',3'-triazol)-1'-yl]-1,3,5-triazine of the formula: as an antidote against phytotoxic effect of herbicide 2,4-dichlorophenoxyacetic acid on sunflower germinated seeds. The proposed substance allows significant increasing roots and hypocotyls length of seedlings and to expand assortment of the known antidotes.

EFFECT: improved and valuable properties of antidote.

2 cl, 2 tbl, 3 ex

FIELD: organic chemistry, medicine, virology.

SUBSTANCE: invention relates to new derivatives of piperidine of the general formula (II): or their pharmaceutically acceptable salts wherein Xa means -C(R13)2-, -C(R13)(R19)-, -C(O)-, and others; Ra means R6a-phenyl or phenyl substituted with methylsulfonyl; R1 means hydrogen atom or (C1-C6)-alkyl; R2 means R7-, R8-, R9-phenyl wherein R7-, R8 and R9 mean substituted 6-membered heteroaryl and others; R3 means R10-phenyl, pyridyl and others; R4 means hydrogen atom, (C1-C6)-alkyl, fluoro-(C1-C6)-alkyl; R6a means from 1 to 3 substitutes taken among the group involving hydrogen, halogen atom, -CF3 and CF3O-; R7 and R8 mean (C1-C6)-alkyl and others; R9 means R7, hydrogen atom, phenyl and others; R10 means (C1-C6)-alkyl, -NH2 or R12-phenyl wherein R12 means hydrogen atom, (C1-C6)-alkyl and others; R13, R14, R15 and R16 mean hydrogen atom or (C1-C6)-alkyl; R17 and R18 in common with carbon atom to which they are bound form spirane ring comprising from 3 to 6 carbon atoms; R19 means R6-phenyl wherein R6 means R6a or methylsulfonyl; R20, R21 and R22 mean hydrogen atom or (C1-C6)-alkyl; R23 means (C1-C6)-alkyl under condition that if Ra means phenyl substituted with methylsulfonyl then Xa can mean the group only. Compounds of the formula (II) possess properties of CCR5-antagonist and can be used in medicine in treatment of HIV-infection.

EFFECT: improved method for treatment, valuable medicinal properties of compounds and composition.

15 cl, 1 dwg, 12 tbl, 15 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to a group of novel derivatives of 4,5-dihydro-1H-pyrazole that are strong antagonists of cannabinoid (CB1) receptor and useful in treatment of diseases associated with disorders of cannabinoid system. Compounds have the general formula (Ia) or (Ib) wherein symbols are given in the invention claim. Also, invention relates to method for synthesis of these compounds, their using, intermediate compounds for synthesis of proposed compounds and to a pharmaceutical composition comprising at least one of these compounds as an active component.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.

15 cl, 1 tbl, 100 ex

FIELD: organic chemistry, chemical technology, biochemistry, pharmacy.

SUBSTANCE: invention relates to novel derivatives of heteroaryl-substituted aminocyclohexane of the formula (I) and their pharmaceutically acceptable salts possessing the inhibitory effect on activity of 2,3-oxydosqualene-lanosterolcyclase (OSC). In the formula (I) V means a simple bond, oxygen atom (O), -CH=CH-CH2- or -C≡C-; m and n = 0-7 independently of one another and m+n = 0-7 under condition that m is not 0 if V means O; o = 0-2; A1 means hydrogen atom, lower alkyl, hydroxy-lower alkyl or lower alkenyl; A2 means lower alkyl, or A1 and A2 are bound and form 5-6-membered cycle, and -A1-A2- means (C4-C5)-alkylene; A3 and A4 mean hydrogen atom independently of one another; A5 means hydrogen atom, lower alkyl; A6 means pyridinyl, pyridazinyl, pyrimidinyl or pyrazinyl optionally substituted with one substitute chosen independently from the group including halogen atom, lower alkyl, lower alkoxy-group and 5-6-membered heteroaryl comprising nitrogen or sulfur atom as a heteroatom, Also, invention relates to a pharmaceutical composition and using proposed compound for preparing medicinal agents. Proposed compounds can be used in treatment of such diseases as hypercholesterolemia, hyperlipemia, arteriosclerosis, vascular diseases, mycosis, parasitic infections, cholelithiasis, tumors and/or hyperproliferative disorders, and/or in disordered tolerance to glucose and diabetes mellitus.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.

24 cl, 7 sch, 28 ex

FIELD: organic chemistry, medicine, neurology, pharmacy.

SUBSTANCE: invention relates to derivatives of pyridazinone or triazinone represented by the following formula, their salts or their hydrates: wherein each among A1, A2 and A3 represents independently of one another phenyl group that can be optionally substituted with one or some groups chosen from the group including (1) hydroxy-group, (2) halogen atom, (3) nitrile group, (4) nitro-group, (5) (C1-C6)-alkyl group that can be substituted with at least one hydroxy-group, (6) (C1-C6)-alkoxy-group that can be substituted with at least one group chosen from the group including di-(C1-C6-alkyl)-alkylamino-group, hydroxy-group and pyridyl group, (7) (C1-C6)-alkylthio-group, (8) amino-group, (9) (C1-C6)-alkylsulfonyl group, (10) formyl group, (11) phenyl group, (12) trifluoromethylsulfonyloxy-group; pyridyl group that can be substituted with nitrile group or halogen atom or it can be N-oxidized; pyrimidyl group; pyrazinyl group; thienyl group; thiazolyl group; naphthyl group; benzodioxolyl group; Q represents oxygen atom (O); Z represents carbon atom (C) or nitrogen atom (N); each among X1, X2 and X3 represents independently of one another a simple bond or (C1-C6)-alkylene group optionally substituted with hydroxyl group; R1 represents hydrogen atom or (C1-C6)-alkyl group; R2 represents hydrogen atom; or R1 and R2 can be bound so that the group CR2-ZR1 forms a double carbon-carbon bond represented as C=C (under condition that when Z represents nitrogen atom (N) then R1 represents the unshared electron pair); R3 represents hydrogen atom or can be bound with any atom in A1 or A3 to form 5-6-membered heterocyclic ring comprising oxygen atom that is optionally substituted with hydroxyl group (under condition that (1) when Z represents nitrogen atom (N) then each among X1, X2 and X3 represents a simple bond; and each among A1, A2 and A3 represents phenyl group, (2) when Z represents nitrogen atom (N) then each among X1, X2 and X3 represents a simple bond; A1 represents o,p-dimethylphenyl group; A2 represents o-methylphenyl group, and A3 represents phenyl group, or (3) when Z represents nitrogen atom (N) then each among X1, X2 and X3 represents a simple bond; A1 represents o-methylphenyl group; A2 represents p-methoxyphenyl group, and A3 represents phenyl group, and at least one among R2 and R means the group distinct from hydrogen atom) with exception of some compounds determined in definite cases (1), (3)-(8), (10)-(16) and (19) given in claim 1 of the invention. Compounds of the formula (I) elicit inhibitory activity with respect to AMPA receptors and/or kainate receptors. Also, invention relates to a pharmaceutical composition used in treatment or prophylaxis of disease, such as epilepsy or demyelinization disease, such as cerebrospinal sclerosis wherein AMPA receptors take part, a method for treatment or prophylaxis of abovementioned diseases and using compound of the formula (I) for preparing a medicinal agent used in treatment or prophylaxis of abovementioned diseases.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.

32 cl, 10 tbl, 129 ex

FIELD: organic chemistry, chemical technology.

SUBSTANCE: invention relates to a method for preparing 3,4-diaryl(hetaryl)maleimides of the formula (I): wherein R means (C1-C4)-alkyl or benzyl, or phenyl; R1 means bromine atom (Br) or aryl, such as phenyl or naphthyl substituted with alkyl, alkoxy-group or halogen atom; unsubstituted hetaryl or substituted, such as thienyl-, benzothienyl-, furyl-, benzofuryl-, pyrrolyl or indolyl- wherein substitutes represent alkyl, alkoxy-, alkylthio-group, halogen atom or trifluoromethyl group; Ar means aryl, such as phenyl or naphthyl substituted with alkyl, alkoxy-group or halogen atom; unsubstituted hetaryl or substituted, such as thienyl-, benzothienyl-, furyl-, benzofuryl-, pyrrolyl or indolyl- wherein substitutes represent alkyl, alkoxy-, alkylthio-group, halogen atom or trifluoromethyl group with exception for 3,4-di-(2,5-dimethyl-3-thienyl)-1-butylmaleimide. Method involves interaction of aryl(hetaryl)boronic acid of the formula: ArB(OH)2 wherein Ar has abovementioned values with N-substituted 3,4-dibromomaleimide of the formula (III): or N-substituted 3-bromo-4-aryl(hetaryl)maleimide of the formula (IV) wherein R and Ar have abovementioned values and with using palladium catalyst in the presence of base in organic solvent medium. Also, invention to some new derivatives of 3,4-diaryl(hetaryl)maleimides that show photochrome properties.

EFFECT: improved preparing method.

7 cl, 2 dwg, 14 ex

FIELD: organic chemistry, medicine, chemical-pharmaceutical industry, pharmacy.

SUBSTANCE: invention relates to a pharmaceutical composition comprising S-isomer of compound of the formula (I) or its pharmaceutically acceptable salts and solvates in common with a pharmaceutically acceptable vehicle. Also, invention relates to a method for synthesis of compound S-isomer of the formula (I), and to a method for treatment of disease relating to the group comprising respiratory diseases, allergic diseases, dermatological diseases, gastroenteric diseases and ophthalmic diseases. The composition provides avoiding adverse sedative effects in treatment of indicated diseases.

EFFECT: valuable medicinal properties of compounds.

14 cl, 6 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention describes derivatives of benzodiazepines of the general formula (I):

wherein X means ordinary bond or ethynediyl group wherein if X mean ordinary bond then R1 means halogen atom or phenyl substituted with halogen atom optionally or (C1-C7)-alkyl group; in case when X means ethynediyl group then R1 mean phenyl substituted with halogen atom optionally; R2 means halogen atom, hydroxy-group, lower alkyl, lower alkoxy-group, hydroxymethyl, hydroxyethyl, lower alkoxy-(ethoxy)n wherein n = 1-4, cyanomethoxy-group, morpholine-4-yl, thiomorpholine-4-yl, 1-oxothiomorpholine-4-yl, 1,1-dioxothiomorpholine-4-yl, 4-oxopiperidine-1-yl, 4-(lower)-alkoxypiperidine-1-yl, 4-hydroxypiperidine-1-yl, 4-hydroxyethoxypiperidine-1-yl, 4-(lower)-alkylpiperazine-1-yl, lower alkoxycarbonyl, 2-di-(lower)-alkylaminoethylsulfanyl, N,N-bis-(lower)-alkylamino-(lower)-alkyl, (lower)-alkoxycarbonyl-(lower)-alkyl, (lower)-alkylcarboxy-(lower)-alkyl, lower alkoxycarbonylmethylsulfanyl, carboxymethylsulfanyl, 1,4-dioxa-8-azaspiro[4,5]dec-8-yl, carboxy-(lower)-alkoxy-group, cyano-(lower)-alkyl, 2-oxo[1,3]dioxolane-4-yl-(lower)-alkoxy-group, 2,2-dimethyltetrahydro[1,3]dioxolo[4,5-c]pyrrole-5-yl, (3R)-hydroxypyrrolidine-1-yl, 3,4-dihydroxypyrrolidine-1-yl, 2-oxooxazolidine-3-yl, carbamoylmethyl, carboxy-(lower)-alkyl, carbamoylmethoxy-, hydroxycarbamoyl-(lower)-alkoxy-, lower alkoxycarbamoyl-(lower)-alkoxy-, (lower)-alkylcarbamoylmethoxy-group; R3 means phenyl, thiophenyl, pyridinyl that are substituted with halogen atom, cyano-group, carbamoyl, imidazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl or isoxazolyl wherein groups of 1,2,3-triazolyl, 1,2,4-triazolyl or isoxazolyl are substituted optionally with (C1-C7)-alkyl or (C1-C7)-alkylsulfanyl, and to their pharmaceutically acceptable salts. Also, invention describes a medicinal agent that is antagonist of mGlu receptors of the group II based on compound of the formula (I). The medicinal agent can be used in treatment and prophylaxis of acute and/or chronic neurological disturbances including psychosis, schizophrenia, Alzheimer's disease, disturbances in cognitive ability and memory damage.

EFFECT: valuable medicinal properties of compounds.

7 cl, 1 tbl, 98 ex

FIELD: organic chemistry, chemical technology, medicine, pharmacy.

SUBSTANCE: invention describes derivatives of benzodiazepine of the general formula (I)

and their pharmaceutically acceptable acid-additive salts wherein X means a ordinary bond or ethynediyl group; when X means ordinary bond then R1 means halogen atom, (lower)-alkyl, (lower)-alkylcarbonyl, (lower)-cycloalkyl, benzoyl, phenyl substituted optionally with halogen atom, hydroxyl, (lower)-alkyl, (lower)-alkoxy-group, halogen-(lower)-alkoxy-group or cyano-group; styryl, phenylethyl, naphthyl, diphenyl, benzofuranyl, or 5- or 6-membered heterocyclic ring representing thiophenyl, furanyl, pyridinyl, dihydropyridinyl, tetrahydropyridinyl which are optionally substituted; when X means ethynediyl group then R1 means hydrogen atom, (lower)-alkyl substituted optionally with oxo-group; (lower)-cycloalkyl substituted with hydroxyl; (lower)-cycloalkenyl substituted optionally with oxo-group; (lower)-alkenyl, optionally substituted phenyl; 5- or 6-membered heterocyclic ring representing thiophenyl, thiazolyl, pyridinyl, dihydropyridinyl, tetrahydropyridinyl or dihydropyranyl and substituted optionally; R3 means phenyl, pyridyl, thiophenyl or thiazolyl which are substituted optionally. These compounds can be used for treatment or prophylaxis of acute and/or chronic neurological diseases, such as psychosis, schizophrenia, Alzheimer's disease, disorder of cognitive ability and memory disorder. Also, invention describes a medicinal agent based on these compounds and a method for preparing compounds of the formula (I).

EFFECT: improved method for preparing, valuable medicinal properties of compounds.

10 cl, 1 tbl, 173 ex

FIELD: organic chemistry, medicine.

SUBSTANCE: invention relates to new 2-aminopyridine derivatives of formula I , wherein R1 is cyano, carboxyl or carbamoyl; R2 is hydrogen, hydroxyl, C1-C6-alkoxy or phenyl; R3 and R4 are aromatic hydrocarbon such as phenyl or naphthyl, 5-14-membered 5-14-membered optionally substituted aromatic group, excepted cases, when (1) R1 is cyano, R2 is hydrogen, and R3 and R4 are simultaneously phenyl;(2) R1 is cyano, R2 is hydrogen, R3 is 4-pyridyl, and R4 is 1-pyridyl; (3) R1 is cyano, R2 is 4-methylphenyl, and R3 and R4 are simultaneously phenyl;(4) R1 is cyano, R2, R3 and R4 are simultaneously phenyl, or salts thereof. Derivatives of present invention have adenosine receptor antagonist activity and are useful in medicine for treatment of irritable bowel syndrome, constipation, and defecation stimulation.

EFFECT: 2-aminopyridine derivatives as adenosine receptor antagonists useful in medicine.

34 cl, 2 tbl, 179 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to derivatives of 1-arenesulfonyl-2-arylpyrrolidine and piperidine of the formula (I):

wherein R1 means hydrogen atom (H), (C1-C7)-alkyl; R2 means furyl, thienyl, pyridyl or phenyl optionally substituted with 1-3 substitutes taken among (C1-C7)-alkyl, (C1-C7)-alkoxy-group, halogen atom, cyano-group, CF3 or -N(R4)2; R3 means naphthyl or phenyl optionally substituted with 1-3 substitutes taken among (C1-C7)-alkyl, (C1-C7)-alkoxy-group, halogen atom, acetyl, cyano-group, hydroxy-(C1-C7)-alkyl, -CH2-morpholine-4-yl, (C1-C7)-alkyloxy-(C1-C7)-alkyl, (C1-C7)-alkyl-N(R4)2 or CF3; R4 means independently of one another hydrogen atom (H), (C1-C7)-alkyl with exception for (RS)-2-phenyl-1-(toluene-4-sulfonyl)pyrrolidine, (RS)-1-(toluene-4-sulfonyl)-2-p-tolylpyrrolidine, N-tosyl-cis-3-methyl-2-phenylpyrrolidine, 3-[1-(toluene-4-sulfonyl)pyrrolidine-2-yl]pyridine and N-tosyl-2-(3,4-dimethoxyphenyl)pyrrolidine, and their pharmaceutically acceptable salts also. Compounds of the formula (I) elicit the effect of agonists or antagonists of metabotropic glutamate receptors that allows their using in pharmaceutical agent useful for treatment or prophylaxis of acute and/or chronic neurological disturbances.

EFFECT: valuable medicinal properties of compounds.

9 cl, 1 tbl, 3 sch, 94 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to a group of new derivatives of 4,5-dihydro-1H-pyrazole of the general formula (I):

wherein R means phenyl, thienyl or pyridyl and these indicated groups can be substituted with (C1-C3)-alkoxy-group or halogen atom; R1 means phenyl that can be substituted with (C1-C3)-alkoxy-group or pyridyl group; R2 means hydrogen atom or hydroxy-group; Aa means one group among the following groups: (i) , (ii) , (iii) , (iv) or (v) ; R4 and R5 mean independently from one another hydrogen atom or (C1-C8)-branched or unbranched alkyl; or R4 means acetamido- or dimethylamino-group or 2,2,2-trifluoroethyl, or phenyl, or pyridyl under condition that R5 means hydrogen atom; R6 means hydrogen atom at (C1-C3)-unbranched alkyl; Bb means sulfonyl or carbonyl; R3 means benzyl, phenyl or pyridyl that can be substituted with 1, 2 or 3 substitutes Y that can be similar or different and taken among the group including (C1-C3)-alkyl or (C1-C3)-alkoxy-group, halogen atom, trifluoromethyl; or R3 means naphthyl, and its racemates, mixtures of diastereomers and individual stereoisomers and as well as E-isomers, Z-isomers and mixture of E/Z-compounds of the formula (I) wherein A has values (i) or (ii), and its salt. These compounds are power antagonists of Cannbis-1 (CB1) receptor and can be used for treatment of psychiatric and neurological diseases. Except for, invention relates to a pharmaceutical composition used for treatment of some diseases mediated by CB1-receptor, to a method for preparing this composition, a method for preparing representatives of compounds of the formula (I) wherein Aa means group of the formulae (i) or (ii), intermediate compounds used for preparing compounds of the formula (I) and to a method for treatment of some diseases mediated by CB1-receptor.

EFFECT: valuable medicinal properties of compounds.

16 cl, 9 ex

FIELD: medicine, pharmacology.

SUBSTANCE: the present innovation deals with correcting affected erythropoiesis in case of severe hypoxia. One should fulfill subcutaneous single injection of propranolol for laboratory mice on the 2nd d after hypoxia modeling at the dosage of 5 mg/kg. The innovation enables to improve the dynamics for reconstructing cellularity and qualitative values of erythroid source of blood formation, increase the number of erythrocytes in peripheral blood at decreasing the production of their pathological forms due to preventing the lesion of commitment precursor cells of erythropoiesis in post-hypoxic period.

EFFECT: higher efficiency of correction.

3 ex, 3 tbl

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