The composition for repelling parasites

 

(57) Abstract:

The invention relates to agriculture and veterinary medicine. The composition for repelling parasites include one of the compounds of formula (I) or one of its acid additive salts and additives that improve the dissemination

compounds on the surface. The composition applied to the skin, hair, or feathers of an animal, place or material from which to repel insect. The proposed composition has a strong and long-lasting repellent effect. 5 C. And 8 C.p. f-crystals, 1 table.

The present invention primarily relates to non-therapeutic method of repelling parasites, based on the application mainly known compounds of formula (I) below. In addition, it relates to deterring parasites compositions which contain these compounds as active ingredient, compounds of formula (I) intended for the preparation of deterring parasites compositions and to the use of compounds of formula (I) for protection against parasites.

With the invention it has been unexpectedly found that compounds of the following formulas (I)

or kislotno oznachaet1-C20alkyl, C1-C20alkoxy, unsubstituted phenyl or phenyl having one or more substituents selected from the series, including1-C3alkyl, C1-C3haloalkyl,1-C3haloalkoxy, halogen, cyano, hydroxyl, alkoxy, amino or nitro;

R1denotes hydrogen, C1-C20alkyl, -C(O)-R3, -C(S)-R4C(O)-O-R5, -C(O)-NH-R6or-C(S)-NH-R7; where R3, R4, R5, R6and R7independently of one another denote WITH1-C10alkyl, acetoxy,1-C10haloalkyl,1-C10alkoxy or1-C10haloalkoxy, or independently from each other represent unsubstituted phenyl or phenyl having one or more substituents selected from the series, including1-C3alkyl, C1-C3haloalkyl,1-C3haloalkoxy, halogen, cyano, hydroxyl, C1-C3alkoxy, amino, Cho, or nitro;

R2and R3independently of one another denote hydrogen, C1-C3alkyl, C1-C3haloalkyl,2-C3haloalkoxy, halogen, cyano, hydroxyl, amino, aryl or nitro;

Radenotes hydrogen, unsubstituted b a t t e, including halogen, cyano, hydroxyl, alkoxy, nitro, phenyl, biphenyl, benzyloxy or phenoxyphenyl, where each of the phenyl, biphenylenes, benzyloxy or phenoxyphenyl groups in turn has one or more substituents selected from the series, including1-C3alkyl, C1-C3haloalkyl, C1-C3haloalkoxy,1-C3alkoxy, halogen, cyano, hydroxyl, amino, aryl or nitro; or denotes a C3-C8cycloalkyl, phenyl, biphenyl, phenoxyphenyl or heterocyclyl, where each of ukazannyh cyclic radicals has one or more substituents selected from the series, including1-C3alkyl, C2-C6alkenyl,1-C3haloalkyl,1-C3haloalkoxy, C1-C3alkoxy, halogen, cyano, hydroxyl, amino, (C1-C3alkyl)2N acetyl or nitro; or denotes a C1-C6alkylaryl, where the aryl radical is unsubstituted or has one or more substituents selected from the series, including1-C3alkyl, C1-C3haloalkyl, C1-C3haloalkoxy, halogen, cyano, hydroxyl or nitro; or denotes a C1-C20alkyl, which depending on the means hydrogen, WITH1-C20alkyl, heterocyclyl or aryl, where each of the cyclic radicals has one or more substituents selected from the series, including1-C3alkyl, C1-C3haloalkyl,1-C3haloalkoxy,2-C6alkenyl, halogen, cyano, hydroxyl, C1-C3alkoxy, amino, (C1-C3alkyl)2N or nitro;

have a pronounced activity against deter parasites. Thanks to the use of compounds according to the invention can be deter most types of parasites that live on humans, animals, or objects in certain places, with numerous compounds falling within the scope of formula (I) are distinguished by the fact that their effectiveness is maintained for a very long period of time.

The compounds of formula (I) having at least one basic centre can form an acid additive salt. They can be formed, for example, with strong inorganic acids such as mineral acids, for example, with perchloro acid, sulfuric acid, nitric acid, nitrous acid, phosphoric acid or a halogen acid, with strong organic carboxylic acids, on the example with acetic acid, dicarboxylic acids, which optionally is unsaturated, for example, oxalic, malonic, succinic, maleic, fumaric or phthalic acid, usually with hydroxycarbonate acids, e.g. ascorbic, lactic, malic, tartaric or citric acid, or benzoic acid, or with organic sulfonic acids, for example, WITH1-C4alkanesulfonyl or arylsulfonate acids, optionally substituted, e.g. by halogen, for example, with methansulfonate or paratoluenesulfonyl acid. The preferred salts are the salts formed from strong acids, especially mineral acids, in particular, with halogen acids model HC1 and NVG.

If there are several deputies, it is assumed that they can be the same or different.

The alkyl groups mentioned in the definitions of the substituents, depending on the number of carbon atoms can be straight or branched chain, their examples are methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tetradecyl, hexadecyl, octadecyl or eicosyl, as well as exile. On the basis of these alkyl groups can be formed alkoxy-, haloalkaline and haloalkoxy.

"Halo" means a halogen and usually denotes fluorine, chlorine, bromine or iodine, preferably fluorine or chlorine, especially chlorine, along with appropriate substituents can contain one or more identical or different halogen atoms.

Halogen-substituted group containing carbon atoms, such as haloalkyl or haloalkoxy, may be partially halogenated or perhalogenated, in the case when there are multiple halogen substituents, they may be identical or different. Examples of haloalkyl considered as a separate group or as a structural element of other groups and compounds, such as haloalkyl are methyl, substituted by one to three fluorine atoms, chlorine and/or bromine, for example, F2or CF3; ethyl substituted by one to five fluorine atoms, chlorine and/or bromine, for example, CH2CF3, CF2CF3, CF2CCl3, CF2CHCl2, CF2F2, CF2CFCl2, CF2CHBr2, CF2CHClF, CF2CHBrF or CC1FCHC1F; propyl or isopropyl substituted one to six fluorine atoms, chlorine and/or 2; and butyl or one of its isomers substituted with one to nine atoms of fluorine, chlorine and/or bromine, for example, CF(CF3)FF3or CH2(CF2)2CF3.

Alkenyl considered as a separate group or as strukturnoi element of other groups and compounds, such as alconox, haloalkyl or haloalkoxy, in each case depending on the specified number of carbon atoms in the group or the connection has either a straight chain, for example, vinyl, 1-methylvinyl, allyl, 1-butenyl or 2-hexenyl or branched chain, for example, Isopropenyl.

Suitable cycloalkyl substituents containing 3-8 carbon atoms and represents, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl or cyclooctyl. Appropriate cycloalkenyl deputies are mono - or polyunsaturated, for example, cyclopentadienyl or cyclooctatetraene. Preferred are cyclopentyl and cyclohexyl.

In the context of the present description aryl denotes phenyl or naphthyl, especially phenyl. These aryl groups may be unsubstituted or have one or more substituents selected from the series, including the alkoxy, halogen, cyano, hydroxyl, amino or nitro, in the case of several deputies they do not necessarily have to be identical; on the contrary, can be mixed substituents.

In the context of the present invention the term "heterocyclyl" denotes an aliphatic or aromatic and condensed with the benzene ring of the cyclic radicals containing at least one atom of oxygen, sulfur or nitrogen. Preferred are 5 - and 6-membered heterocycles. Usually the heterocycle contains substituents, for example, DIOXOLANYL, pyrrolidinyl, piperidinyl, morpholinyl, pyridyl, peril, furyl, thienyl, imidazolyl, tetrahydrofuryl, tetrahydropyranyl, tetrahydropyranyl, dihydrofuran, dihydropyran, benzofuran, benzothiazyl, isoxazolyl, oxazolyl, thiazolyl, oxazolyl, oxazolidinyl, indolyl, imidazolyl, imidazolidinyl and dioxane. Preferred are unsubstituted heterocycles, or bearing one or two halogen atom, in this case, halogen denotes fluorine, chlorine or bromine, but especially chlorine. Among these heterocyclyl radicals should be emphasized pyrrolidinyl, piperidinyl, pyridyl, peril, furyl, thienyl, tetrahydrofuryl, benzofuran and sensational.

R1denotes hydrogen, C1-C6alkyl, -C(O)-R3or-C(S)-R4; where R3and R4independently of one another denote WITH1-C3alkyl, acetoxy,1-C3haloalkyl or independently from each other represent unsubstituted phenyl or phenyl having one or more substituents selected from the series, including1-C3alkyl, C1-C3haloalkyl or halogen;

R2and R3independently of one another denote hydrogen or C1-C3alkyl;

Radenotes hydrogen, C5-C20alkyl, C3-C8cycloalkyl or phenyl, where each of the cyclic radicals is unsubstituted or has one or more substituents selected from a range, including C1-C3alkyl, C1-C3haloalkyl,1-C3alkoxy, halogen, amino, (C1-C3alkyl)2N or acetyl; and

Rbdenotes hydrogen, unsubstituted phenyl or phenyl having one or more substituents selected from the series, including1-C3alkyl, C1-C3haloalkyl, C1-C3alkoxy, halogen, amino or (C1-C3alkyl)21denotes-C(O)-R3where R3denotes unsubstituted phenyl or phenyl having one or more substituents selected from the series, including1-C3alkyl, especially methyl, ethyl or isopropyl, and the other substituents have the meanings indicated above for formula (I) and their acid additive salt. Also of interest are compounds of formula (I), where R2and R3independently of one another denote hydrogen or methyl and the remaining substituents have the meanings indicated above for formula (I) and their acid additive salt. Among the above compounds of formula (I) is most preferred are compounds where Rastands WITH5-C20alkyl, benzoyloxymethyl, 2,3-dihydrobenzo(b)furreal-2, unsubstituted phenyl or phenyl having one or more substituents selected from a range, including C1-C3alkyl, methoxy or chlorine; including their acid additive is a pit chain; including their acid additive salt. Active ingredients in a free form is a much more preferable compared to the acid additive salts. Each member of the group the following individual compounds is particularly preferred due to its pronounced activity of the compounds marked with an asterisk are new and are an integral part of the present invention: 2-[n-(1-hydroxyhexyl)]piperidine*, 2-[n-(1-hydroxyethyl)]piperidine*, 2-[n-(1-hydroxyacyl)]piperidine*, 2- [n-(1-hydroxyaryl)]piperidine, 2-[n-(1-hydroxyacyl)]piperidine, 2- [n-(1-hydroxyphenyl)]piperidine, 2-[n-(1-hydroxydiphenyl)]piperidine, 2-[n-(1-hydroxytriazine)]piperidine, 2- [n-(1-hydroxytetrazole)]piperidine, 2-[n-(1-hydroxypentanal)] piperidine, 2-[n-(1-hydroxyhexyl)]piperidine, 2-[n-(1-hydroxycamptothecin)]piperidine, 2-[n-(1-hydroxystearic)] piperidine, 2-[n-(1-hydroxynonenal)]piperidine, 2-[n-(1-hydroxyalkyl)]piperidine, 2-[n-(1-hydroxyanisol)]piperidine, 2- [(1-cyclopentyl)(1-hydroxy)methyl]piperidine, 2-[(1-phenyl)(1-hydroxy)methyl]-4-tert-butylpiperazine, 2-[(1-phenyl)(1-hydroxy) methyl]piperidine, N-methyl-2-[(1-phenyl)(1-hydroxy)methyl]piperidine, 2- [(1-diphenyl)(1-hydroxy)methyl]piperidine, 2-[(1-phenyl)(1-[2,3-diphenyl]) (1-hydroxy)methyl]piperidine, 2-[(1-[4-isopropylphenyl])(1-hydroxy) methyl]piperidine, N-methyl-2-[(1-[4-isopropylphenyl])(1-hydroxy) methyl]piperidine, 2-[(1-[4-methoxyphenyl])(1-hydroxy)methyl] piperidine, 2-[(1-[benzyloxyethyl])(1-hydroxy)methyl]piperidine, 2- [(1-thienyl)(1-hydroxy)methyl]piperidine, 6,6-dimethyl-2-[(1-[4-chlorophenyl])(1-hydroxy)methyl]piperidine, N-acetyl-2-[(1-hydroxy)(1-undecyl)]piperidine* or N-etoxycarbonyl-2-[(1-hydroxy)(1-undecyl)] piperidine*.

In Chemical Abstracts, volume 107, No. 23, December 7, 1987, Columbus, PCs Ohio, U.S.; abstract No. 215128 described among other compounds deoxynojirimycin as a repellent with weak activity against certain types of insect pests of plants. In GB-A 2071653 described compounds having structural similarity to the compounds of formula I of the present invention. They can be used in marine and fresh water to reduce the growth of algae, barnacles or fungi. In EP 0281908 described the use of certain derivatives of aminoalcohols, for example, some piperidinol as repellents for insects and mites.

In the context of the present invention the term "parasite" refers primarily to insects, spider clamp and Parasitiformes the clamp. They include insects of the orders: Lepidop is to mark such parasites that cause trouble humans or animals and carry pathogens, for example flies such as Musca domestica, Musca vetustissima, Musca autumnalis, Fannia canicularis, Sarcophaga carnaria, Lucillia cuprina, Hypoderma bovis, Hypoderma lineatum, Chrysomia chloropyga, Dermatobia hominis, Cochliomyia hominivorax, Gasterophilus intestinalis, Oestrus ovis, Stomoxys calcitrans, Haemotobia irritans and small Diptera (Nematocera), such as the units Culicidae, Simuliidae, Psychodidae, as well as blood-sucking parasites, for example fleas, such as Ctenocephalides felis and Ctenocephalides canis (cat and dog fleas), Xenopsylla cheopis, Pulex irritans, Dermatophilus penetrans, lice, such as Damalina ovis, Pediculus humanis, stinging flies and horseflies (Tabanidae), Haematopota spp., such as Haematopota pluvialis, Tabanidea spp., such as Tabanus nigrovittatus, Chrysopsinae spp., such as Chrysops caecutiens, flies TSE-TSE, such as various kinds R. Glossinia, stinging insects, as well as, cockroaches, such as Blatella germanica, Blatta orientalis, Periplaneta americana, spider mites, such as Dermanyssus gallinae, Sarcoptes scabiei, Psoroptes ovis and Psorergates spp., and finally, Parasitiformes mites, but interest parasites are not restricted to this list. Parasitiformes ticks (hereinafter simply "ticks") belong to the order Acarina. Well-known representatives of mites include, for example, to R. R. Boophilus, Amblyomma, Anocentor, Dermacentor, Haemaphysalis, Hyalomma, Ixodes, Rhipicentor, Margaropus, Rhipicephalus, Argas, Otobius and Ornitodorus, etc. which, preferably infect warm-blooded belly is and, such as chickens, turkeys and geese, fur-bearing animals such as mink, foxes, chinchillas, rabbits and so on, as well as domestic animals such as cats and dogs, and people.

Ticks can be divided into hard and soft ticks and they are characterized by the fact that it is able to infect one, two or three animal hosts. They attach to a passing animal host and suck blood or fluid from the body. Completely sucked female ticks drop from an animal host and lay large numbers of eggs (2000-3000) into a suitable opening in the floor or in another secure place where hatched larvae. They in turn are looking for an animal host to suck blood. Larvae of mites that infect only one animal host, molts twice and turn into nymphs and eventually into adult ticks without leaving the selected host. Larvae of mites that infect two or three animal hosts, leave the animal after blood meal, fade in any place in the environment and into nymphs or adult ticks seek second or third owner in order to suck his blood.

Mites are the reason for the transfer and distribution around the world numerous who treats R. R. Boophilus, Rhipicephalus, Ixodes, Hyalomma, Amblyomma and Dermacentor. They are carriers of diseases caused by bacteria, viruses, Rickettsia and protozoa that cause tick paralysis and tick toxicosis.

Even one tick can cause paralysis, as his saliva penetrates into an animal host during suckling. Diseases caused by ticks are normally transferred mites that infect multiple animal hosts. Diseases such as babesiosis, anaplasmosis, East coast fever and infectious hydropericardium, cause the deaths or illnesses of a large number of Pets and farm animals all over the world. In many countries with temperate climate ticks carry the pathogen dangerous chronic Lyme disease from wild animals to humans. In addition to the transfer of diseases ticks are caused large economic losses in cattle production. Losses are not limited to the death of animals, but they also include damage to the skin, reduced growth, reduced milk production and reduced meat quality. Although the harmful effects of infection in animals ticks known for many years, and has made great progress in implementing programmes for the control of ticks, so far not Mazdaspeed resistance to chemical active substances.

Infestation by fleas of domestic animals and Pets also still is for the owner of the problem that cannot satisfactorily be solved or can be solved only by using a substantial cost. As ticks, fleas are not only troublesome, but also are carriers of diseases they transmit various fungal disease from an animal host to another animal to the owner and the owner of the animal, especially in humid areas with a warm climate, for example, in the Mediterranean, in the southern part of the USA, etc. are at risk primarily people with a weakened immune system or children, whose immune system is not yet fully developed. Because fleas are characterized by a complex life cycle, none of the known methods of controlling fleas cannot be considered entirely satisfactory, primarily because the majority of known methods mainly focus on the fight against adult fleas in the fur and completely not affected by the various immature stages of fleas that live not only in animal fur, but also in the floor, carpets, bedding for animals, in chairs, in the garden and in all other places, which contacts an infected animal is erodov time. Success usually depends on the processing not only of the infected animal, such as dogs or cats, but at the same time and all other places which are visited by an infected animal.

This complex process is not necessary when the use of compounds of formula (I) according to the present invention, since the main advantage of the considered compounds of formula (I) is that they have a very high efficiency and at the same time very low toxicity for parasite targets, and for warm-blooded animals. This is due to the fact that their activity is not based on the destruction of the parasite target, and on the implementation of protection against him before the parasite attacks, stings, bites or otherwise injures the body-Hosain. The presence of compounds of the formula (I) presented in the present description, apparently repels parasites so that they immediately leave the treated place, not biting or woman's son by striking, or not infect the treated animal host. Striking only that the effect occurs when the parasite within a short period of time it comes in contact with the active substance. After a brief contact of the parasite avoids further contact with the current prophetic is A (N,N-diethyl-m-toluamide), which, although it has a high efficiency, but evaporates quickly and must be reapplied after about 2 h, which is not suitable for long term treatment of animals. The use of active substances according to the present invention is also convenient because they have virtually no smell.

Although the active substances according to the present invention can of course be mixed with other substances having the same spectrum of activity, or parasiticides or other improves the activity of substances to achieve an even more enhanced or prolonged action, and to apply then, but, unlike many of the compounds known in this field, this is not required, since they already combine all preferred properties.

If you want not only to not let the parasite, but also to destroy it, of course, this can be achieved by adding the appropriate insecticides and/or acaricides. In reality, however, in most cases this is not required.

The active substances according to the present invention preferably is used in diluted form. Typically, the final preparative - matter ranges from 0.1 to 95 wt.%, preferably from 0.5 to 90 wt.%.

Since the active substances in many cases put on warm-blooded animals and, of course, they come into contact with the skin, suitable excipients for the compositions are excipients and formulation used in cosmetics. They can be applied in the form of solutions, emulsions, ointments, creams, pastes, powders, sprays, etc.

For treatment of farm animals or pet animals, such as cows, horses, donkeys, camels, dogs, cats, poultry, sheep, goats, and so on, especially suitable for the so-called composition for irrigation or for spot treatment; such liquid or semi-solid compositions have the advantage that they should be applied only on small areas of skin or plumage and, through its presence as a component of improving distribution on the surface of the oil or other which improves the distribution of surface additives, they dispersed themselves across the surface of the skin or plumage, without requiring any extra effort, and have an effect on the entire surface.

Of course, such compositions can be processed inanimate objects such as clothing or cells infected by parasites.

To combat cockroaches can be sprayed or suffused their habitats, usually representing the cracks in the walls, furniture, etc. Because cockroaches are very active insects and almost impossible to remove them completely, it is recommended that when applying the active compounds of the present invention to additionally apply an insecticide with activity against cockroaches.

For use in humans can add the essence, having a pleasant smell, such as perfume, in order to make the treatment more pleasant.

The following examples of compositions and methods of use of active substances according to the invention serve to illustrate the invention without limiting its scope.

In particular, the preferred compositions are prepared in the following way:

Example compositions 1

Deterring parasites composition in the form of a lotion for application to the skin is prepared by mixing 30 parts of one of the active substances according to the invention, shown in the table, with 1.5 parts of odorants and 68.5 parts of isopropanol, the latter component may be replaced by ethanol.

Example composition 2

Deterring drug formulation in the form of filling the aerosol container, containing 50% solution of the active substance, comprising 30 parts of one of the active substances according to the invention, shown in the table, 1.5 parts of perfume and 68.5 parts of isopropanol, and 50% of the gas propellant Frigen 11/12 (halogenated hydrocarbon).

An example of the composition 3

Deterring parasites composition in the form of an aerosol for spraying the skin is produced by cooking preparative form filler aerosol container, containing 40% solution of the active substance, comprising 20 parts of one of the active substances according to the invention, shown in the table 1 part perfumes and 79 parts of isopropanol and 60% of the gas propellant, which is a mixture of propane/butane (in the ratio 15:85).

As an example, the following table presents some of the compounds falling within the scope of formula (I), which can be used according to the invention, however, it should be borne in mind that this list is not complete. Compounds in italics are new and are an integral part of the invention. Other compounds, as well as methods for their preparation, are known from the literature. Below is an example of retrieving serves only for the purpose Illus imeeetsja in medicine to treat various diseases, for example, as bronchodilators, antiallergic agents, analgesics, diuretics, antidepressants, dopamine antagonists, etc. Some of them have herbicide or fungicide activity. New representative compounds falling within the scope of formula (I), which are italicized in the table can be obtained analogously to known compounds. Representative compounds have in column "R" acid is enclosed in parentheses represent an acid additive salt. The new compounds of formula (I) can be obtained similarly to the substances described in GB-A-2071653, or by using the following example.

Example: getting 2-(n-decelerate)piperidine according to the following reaction scheme:

The mixture containing at 0.31 mole of bromonidine in 350 ml of anhydrous diethyl ether, is mixed by adding dropwise, at 25 ° C with a solution containing 0.3 mole of 2-lepirudin in 250 ml of anhydrous ethyl ether. The reaction mixture was incubated for 2 h at the temperature of reflux distilled, then cooled to 10 ° C and mixed with an aqueous solution of sulfuric acid (70 ml water/200 ml 5 N. H2SO4). The reaction product is extracted with diethyl ether. Essential fastreroute in vacuum. Get 72.5 g (yield of 97.7%) compounds In the form of oils, which are used in the next stage without further purification. At this stage, the mixture containing 4.6 g connection and 0.25 g RTO2in 45 ml of acetic acid, mixed with gaseous hydrogen by hydrogenation at room temperature. After 17 h all solid components are filtered out and the liquid phase, mixed with 2 N. solution of caustic soda. Then extracted with dichloroethane. The organic phase is washed several times with saturated sodium chloride solution, dried over magnesium sulfate, filtered and concentrated in vacuo. The residue is mixed with methanol, resulting mentioned in the title compound precipitates as amorphous powder. After filtration and drying under vacuum to obtain 2.8 g (yield 62%) specified in the connection header, tPL61-S.

The following table AC denotes acetyl, ASO denotes the atomic charges, Me denotes methyl, MeO denotes methoxy, Et denotes ethyl, tO denotes ethoxy, R denotes propyl, RO denotes propoxy, PR represents n-propyl, iP denotes isopropyl, denotes butyl, PV denotes n-butyl, IB represents isobutyl, sB denotes a second-butyl, tB denotes a tert-butyl, Ph denotes the dryer is Neh denotes cyclohexyl, sner denotes cycloheptyl, SOS indicates cyclooctyl and me denotes a methylene.

Biological examples:

Test method deterring parasites substances using arena

This method is carried out on titration tablets with 6 holes with a diameter of 5 cm each, using a computerized video system. Each well tiralongo tablet lined circles of filter paper or other suitable media. Designed to test the compound of formula (I) is dissolved in methanol, acetonitrile or other suitable solvent for membrane not easily soluble compounds used sonication and heating. Dissolved test compound in an amount of from 1 to 100 µg/cm2placed in the center of the filter paper on a square or a circle with an area of about 2.4 cm2. In 4 of the 6 holes make various test compounds or the same test compound in various concentrations (e.g., 1, 3, 2, 5, 10 and 20 µg/cm2). The fifth hole is treated with DETA (N,N-diethyl-m-towed) as a reference. In the sixth hole making pure solvent and she Slu is the ago) parasites in respect of which assess the activity of compounds, for example, ticks, and the system is covered by a glass plate and placed under a video camera. At intervals of 5 with camera makes the individual images of all 6 holes. For the qualitative evaluation of these images is looking at non-stop in the form of a continuous film, visually observing the movement of parasites on filter paper and comparing them with the movements in the test hole # 6 or 5th hole containing the reference. So make qualitative conclusion about move if used in the test parasites equally over the entire surface of the filter paper and do not pay attention to test the connection, or they avoid the treated area and during what period of time this is happening and what is the impact of the dilution of test compounds on the behavior used in the test parasites. In this way identify the neutral compound and a compound which has a repellent effect. At the same time, assess the duration of action of the tested compounds and compared with the duration of the benchmark. By applying all of the images taken for one hole, each other get areas with different densities. This x is thus, using the method of Wilcoxon (Willcoxon) get a quantitative assessment compared with control and standard. The compounds shown in the table, for example, connection№№1.22-1.41, 1.44, 1.45, 1.59, 1.87, 1.89, 1.95, 1.96, 1.97, 1.101, 1.138 and 1.139, have a very high activity.

The test using the arena to assess in vitro activity against Amblyomma hebraeum or variegatum (nymphs)

Testing is conducted according to the above method, making each hole about 25-50 nymphs. 10 mg of dissolved test compound is applied to the size of 2.4 cm2. Evaluation of the video shows that the compounds of formula (I) possess a strong repellent action against Amblyomma nymphs, which lasts much longer than the effect of DETA. The most pronounced long-lasting effect has, for example, connection№№1.26-1.36, 1,40, 1.45, 1.47, 1.95, 1.96, 1.97, 1.137 and 1.139 even at a concentration of 3.2 ág/cm2.

The test using the arena to assess in vitro activity against Boophilus microplus Biarra (larvae)

Testing is conducted according to the above method, making each hole about 60-100 larvae. 10 mg of dissolved test compound is applied to the size of 2.4 cm2. Ocenenie larvae of Boophilus, which lasts much longer than the effect of DETA. The most pronounced long-lasting effect has, for example, connection№№1.26-1.36, 1.40, 1.45, 1.47, 1.95, 1.96, 1.137, 1.139, 1.140, 1.141, 1.142 and 1.143 even at a concentration of 10 µg/cm2.

The test using the arena to assess in vitro activity against Rhipicephalus sanguineus (nymphs)

Testing is conducted according to the above method, making each hole about 40-50 nymphs. Evaluation of the video shows that the compounds according to the invention have good repellent effect. In particular, the compounds are characterized by full-repellent effect, which lasts much longer than the effect of DETA. The most pronounced long-lasting effect has, for example, connection№№1.27, 1.29, 1.32, 1.34, 1.40, 1.45, 1.59, 1.137 and 1.139 even at a concentration of 10 µg/cm2.

Using similar devices for the experiment, appreciate the attractive activity of the same test compounds against various types of flies, such as Musca domestica. The test results show that these compounds have a strong repellent effect even for such test models.

1. Non-therapeutic with the ASS="ptx2">

or one of its acid additive salts

where R is hydrogen, C1-C20alkyl or-C(O)-R8where R8stands WITH1-C20alkyl, C1-C20alkoxy, unsubstituted phenyl or phenyl having one or more substituents selected from the series, including1-C3alkyl, C1-C3haloalkyl,1-C3haloalkoxy, halogen, cyano, hydroxyl, alkoxy, amino or nitro;

R1denotes hydrogen, C1-C20alkyl, -C(O)-R3, -C(S)-R4C(O)-O-R5, -C(O)-NH-R6or-C(S)-NH-R7where R3, R4, R5, R6and R7independently of one another denote WITH1-C10alkyl, acetoxy,1-C10haloalkyl,1-C10alkoxy or1-C10haloalkoxy, or independently from each other represent unsubstituted phenyl or phenyl having one or more substituents selected from the series, including1-C3alkyl, C1-C3haloalkyl,1-C3haloalkoxy, halogen, cyano, hydroxyl, C1-C3alkoxy, amino, Cho, or nitro;

R2and R3independently of one another denote hydrogen, C1-C3alkyl,C1- adenotes hydrogen, unsubstituted WITH1-C20alkyl or C1-C20alkyl having one or more substituents selected from the series comprising halogen, cyano, hydroxyl, alkoxy, nitro, phenyl, biphenyl, benzyloxy or phenoxyphenyl, where each of the phenyl, biphenylenes, benzyloxy or phenoxyphenyl groups, in turn, is unsubstituted or has one or more substituents selected from the series, including1-C3alkyl, C1-C3haloalkyl,1-C3haloalkoxy,1-C3alkoxy, halogen, cyano, hydroxyl, amino, aryl or nitro; or denotes a C3-C8cycloalkyl, phenyl, biphenyl, phenoxyphenyl or heterocyclyl, where each of these cyclic radicals is unsubstituted or has one or more substituents selected from the series, including1-C3alkyl, C2-C6alkenyl,1-C3haloalkyl, C1-C3haloalkoxy,1-C3alkoxy, halogen, cyano, hydroxyl, amino, (C1-C3alkyl)2N acetyl or nitro; or denotes a C1-C6alkylaryl, where the aryl radical is unsubstituted or has one or more substituents, vybrannnogo, cyano, hydroxyl or nitro; or denotes a C1-C20alkyl, which depending on the number of carbon atoms contains an oxygen atom in one or more positions;

Rbdenotes hydrogen, C1-C20alkyl, heterocyclyl or aryl, where each of the cyclic radicals is unsubstituted or has one or more substituents selected from the series, including1-C3alkyl, C1-C3haloalkyl,1-C3haloalkoxy,2-C6alkenyl, halogen, cyano, hydroxyl, C1-C3alkoxy, amino, (C1-C3alkyl)2N or nitro;

applied topically together with the additive that improves the distribution of compounds on the surface of your skin, hair, or feathers warm-blooded animal.

2. The method according to p. 1, according to which is applied the compound of formula (I) or one of its acid additive salts, where R denotes hydrogen or C1-C6alkyl;

R1denotes hydrogen, C1-C6alkyl, -C(O)-R3or-C(S)-R4where R3and R4independently of one another denote C1-C3alkyl, acetoxy, C1-C3haloalkyl or independently of one another denote carried3alkyl, C1-C3haloalkyl or halogen; R2and R3independently of one another denote hydrogen or C1-C3alkyl; Radenotes hydrogen, C5-C20alkyl, C3-C8cycloalkyl or phenyl, where each of the cyclic radicals is unsubstituted or has one or more substituents selected from a range, including C1-C3alkyl, C1-C3haloalkyl, C1-C3alkoxy, halogen, amino, (C1-C3alkyl)2N or acetyl; Rbdenotes hydrogen, unsubstituted phenyl or phenyl having one or more substituents selected from a range, including C1-C3alkyl, C1-C3haloalkyl, C1-C3alkoxy, halogen, amino or (C1-C3alkyl)2N; including their acid additive salt.

3. The method according to any of the p. 1 or 2, which used the compound of formula (I) or one of its acid additive salts, where R denotes hydrogen and the other substituents have the meanings specified for formula (I).

4. The method according to any of paragraphs.1-3, according to which is applied the compound of formula (I) or one of its acid additive salts, where R1denotes-C(O)-R3, alkyl, especially methyl, ethyl or isopropyl, and the other substituents have the meanings specified for formula (I).

5. The method according to any of paragraphs.1-4, according to which is applied the compound of formula (I) or one of its acid additive salts, where R2and R3independently of one another denote hydrogen or methyl and the remaining substituents have the meanings specified for formula (I).

6. The method according to any of paragraphs.1-5, according to which is applied the compound of formula (I) or one of its acid additive salts, where Rastands WITH5-C20alkyl, benzoyloxymethyl, 2,3-dihydrobenzo(b)furreal-2, unsubstituted phenyl or phenyl having one or more substituents selected from a range, including C1-C3alkyl, methoxy or chlorine.

7. The method according to any of paragraphs.1-6, according to which is applied the compound of formula (I) or one of its acid additive salts, where Rastands WITH7-C20direct chain.

8. The method according to p. 1, where the applied active substance represents one of the following compounds or one of its acid additive salts of:

2-[n-(1-hydroxyhexyl)]piperidine, 2-[n-(1-hydroxyethyl)] piperidine, 2-[n-(1-hydroxyacyl) is-(1-hydroxydiphenyl)]piperidine, 2-[n-(1-hydroxytriazine)]piperidine, 2 - [n-(1-hydroxytetrazole)]piperidine, 2-[n-(1-hydroxypentanal)]piperidine, 2-[n-(1-hydroxyhexyl)]piperidine, 2-[n-(1-hydroxycamptothecin)] piperidine, 2-[n-(1-hydroxystearic)]piperidine, 2-[n-(1-hydroxynonenal)]piperidine, 2-[n-(1-hydroxyalkyl)]piperidine, 2-[n-(1-hydroxyanisol)] piperidine, 2-[(1-cyclopentyl)(1-hydroxy)methyl]piperidine, 2-[(1-phenyl)(1-hydroxy)methyl]-4-tert-butylpiperazine, 2-[(1-phenyl)(1-hydroxy)methyl]piperidine, N-methyl-2-[(1-phenyl)(1-hydroxy)methyl]piperidine, 2-[(1-diphenyl)(1-hydroxy)methyl]piperidine, 2-[(1-phenyl)(1-[2,3-dihydrobenzo(b)furry](1-hydroxy)methyl]piperidine, N-methyl-2-[(1-[4-were])(1-hydroxy)methyl]piperidine, 2-[(1-[4-were])(1-hydroxy)methyl]piperidine, 2-[(1-[4-isopropylphenyl])(1-hydroxy)methyl]piperidine, N-methyl-2-[(1-[4-isopropylphenyl])(1-hydroxy)methyl]piperidine, 2-[(1-[4-methoxyphenyl])(1-hydroxy)methyl] piperidine, 2-[(1-[benzyloxyethyl])(1-hydroxy)methyl]piperidine, 2-[(1-thienyl)(1-hydroxy)methyl]piperidine, 6,6-dimethyl-2-[(1-[4-chlorophenyl])(1-hydroxy)methyl]piperidine, N-acetyl-2-[(1-hydroxy)(1-undecyl)]piperidine or N-etoxycarbonyl-2-[(1-hydroxy)(1-undecyl)] piperidine.

9. The method according to any of paragraphs.1-8, whereby the compound of formula (I) is applied in the form of compositions for irrigation is by their absence, providing for the application of an effective amount of the compounds of formula (I) according to any one of paragraphs. 1-8 on the site or material from which to repel insect.

11. The composition for repelling parasites containing the compound of formula (I) according to any one of paragraphs.1-8 and additive to improve the distribution of compounds over the surface.

12. A method of obtaining a composition for repelling parasites, providing a mixture of compounds of formula (I) according to any one of paragraphs.1-8 with the addition that improves the distribution of compounds over the surface.

13. The compound of formula (I) to deter parasites on warm-blooded animal selected from the group comprising

2-[n-(1-hydroxyhexyl)]piperidine, 2-[n-(1-hydroxyethyl)] piperidine, 2-[n-(1-hydroxyacyl)]piperidine, N-acetyl-2-[(1-hydroxy)(1-undecyl)]piperidine and N-etoxycarbonyl-2-[(1-hydroxy) (1-undecyl)]piperidine.

 

Same patents:

The invention relates to new 4-substituted piperidines General formula (I) in which R1and R2represent aryl radicals, substituted or not substituted, which are obtained as racemic mixtures or as pure enantiomers

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and their pharmaceutically acceptable salts, where R1is hydrogen, C1-C6-alkyl, C2-C6alkenyl, C3-C8-cycloalkyl, C6-C10aryl that may be substituted for CH3, halogen, OR5where R5- C1-C6-alkyl, C1-C2-alkyl-heteroaryl containing as heteroatoms of S, N or O; And a is phenyl, substituted carbonyl or amino group; - C6-C10-aryl or C5-C10-heteroaryl containing as heteroatoms of S, N or O

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