Derivatives of 8-methoxy-[1,2,4]triazolo[1,5-a]pyridine and pharmaceutical preparation based on thereof

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention describes novel derivatives of 8-methoxy[1,2,4]triazolo[1,5-a]pyridine of the general formula (I): wherein R1 means unsubstituted phenyl or phenyl substituted with one substitute chosen from group including halogen atom, trifluoromethyl, (lower)-alkyl, (lower)-alkoxy-, acetylamino-group, acetyl, (lower)-alkenyl, -C(O)O-(lower)-alkyl or thio(lower)-alkyl, or thiophenyl possibly substituted with halogen atom, or indolyl; R2 means unsubstituted phenyl or phenyl substituted with a single substitute chosen from group including halogen atom, (lower)-alkyl, halogen-(lower)-alkyl or (lower)-alkoxy-group, or thiophenyl possibly substituted with (lower)-alkyl, their pharmaceutically acceptable salts, and pharmaceutical preparation based on thereof. Novel compounds possess antagonistic effect on adenosine A2A-receptors and can be used in medicine for stimulation of the central nervous system activity and as enhancers of cognitive ability.

EFFECT: valuable medicinal properties of compounds and pharmaceutical preparation.

10 cl, 1 tbl, 1 ex

 

The present invention relates to compounds of General formula

where R1means phenyl or thiophenyl, which are not substituted or substituted by one or two substituents selected from the group comprising halogen, trifluoromethyl, (ness.)alkyl, (ness.)alkoxy, acetylamino, acetyl, (ness.)alkenyl, -C(O)O-(ness.)alkyl and thio(ness.)alkyl, R2means phenyl or thiophenyl, which are not substituted or substituted by one or two substituents selected from the group comprising halogen, (ness.)alkyl, halogen(ness.)alkyl and (ness.)alkoxy, and to their pharmaceutically acceptable salts.

It has been unexpectedly found that compounds of General formula I are ligands of the adenosine receptor.

Adenosine modulates many physiological functions by interacting with surface receptors on specific cells. The use of adenosine receptors as targets of drugs was first described in 1982 in structural and metabolic against adenosine close bioactive nucleotides: adenosine triphosphate (ATP), adenosine diphosphate (ADP), the monophosphate (AMP) and cyclic monophosphate (camp), biochemical meteorous agent of S-adenosyl-L-methionine (S-AM), and structurally close to the coenzymes NAD, f is D and coenzyme A, and also RNA. Adenosine and related compounds have important roles in regulating many aspects of cellular metabolism and modulation of various types of activity of the Central nervous system,

Receptors adenosine receptors are divided into A1, A2AAnd2Band a3belonging to the family of receptors coupled with G-proteins. Activation of adenosine receptors initiates the mechanism of signal transmission. These mechanisms are dependent on G-protein associated with the receptor. Each of the subtypes of adenosine receptors, as a rule, characterized by the adenylate cyclase effector system that uses as a secondary messenger camp. Receptors A1and a3associated with Gi-proteins that inhibit adenylate cyclase, which leads to lower intracellular level of camp, while the receptors And2Aand A2Bpaired with Gs-proteins and activate adenylate cyclase, which increases intracellular levels of camp. It is established that the system of receptor-A1includes activation of phospholipase C and modulation of potassium and calcium ion channels. Subspecies receptor And3besides binding to adenylate cyclase, also stimulates phospholipase C and thus activates calcium ion channels.

Currently, the cloned receptor-a1(326-328 amino acid residues) many of the species (dog, human, rat, dog, chicken, cattle, Guinea pigs), and 90-95% amino acid sequence was identical in many species of mammals. In addition, the cloned receptor-A2A(409-412 amino acid residues) dog, rat, human, Guinea pigs and mice. Cloned the receptor And2B(332 amino acid residue) between human and mouse, and receptor-a2B45% homologous receptors A1and A2Aman. Cloned the receptor And3(317-320 amino acid residues) of human, rat, dog, rabbit and sheep.

It is assumed that the receptor subtypes A1and a2Aplay complementary roles in the regulation of adenosine release of chemical energy. Adenosine, which is a product of metabolic transformation of ATP diffuses out of the cell and acts on the local level, activating adenosine receptors, which stimulate the reduction of oxygen demand (A1or the increase in the supply of oxygen (A2Aand, thus, regulating the balance between energy production and demand in the tissues. The result of the actions of both subtypes of receptors is to increase the amount of oxygen available to the tissues, and protect cells from damage caused by short-term imbalances in the flow of oxygen. One important function is s endogenous adenosine is the prevention of damage during trauma such as hypoxia, ischemia, hypotension, and seizures.

In addition, it was found that the binding of agonist adenosine receptor with fat cells expressing the receptor And3rats leads to increased concentrations of Insectivora and intracellular calcium, which causes the antigen-induced secretion of inflammatory mediators. Therefore, receptor-a3participates in mediating asthma attacks and other allergic reactions.

In addition, adenosine is a neuromodulator that are crucial in the modulation of the molecular mechanisms underlying many aspects of the physiological functions of the brain by mediating an inhibitory processes in the Central nervous system. The enhanced release of neurotransmitters occurs when an injury such as hypoxia, ischemia and seizures. Finally, these neurotransmitters are responsible for the degeneration of nerve tissue and death of neurons, which leads to brain damage or death of the individual. Therefore, agonists of receptor-A1that mimic the inhibitory action of adenosine on cells of the Central nervous system, can be used as neuroprotective agents. It is assumed that adenosine is an endogenous anticonvulsant agent, inhibiting the release of glutamate is C of excited neurons and inhibiting the start of neurons. Therefore, agonists of adenosine can be used as antiepileptic agents. Antagonists of adenosine stimulate the activity of the Central nervous system and are effective as enhancers of cognitive abilities. Selective antagonists of A2Ahave a therapeutic effect in the treatment of various forms of dementia, such as Alzheimer's disease, and are used as neuroprotective agents. Antagonists adenozinove receptor And2inhibit the release of dopamine from synaptic nerve endings and reduce locomotor activity and, therefore, alleviate the symptoms of Parkinson's disease. The Central action of adenosine is also due to the molecular mechanism underlying the sedative action, hypnosis, schizophrenia, anxiety, pain, respiration, depression and abuse of drugs. Therefore, medicines acting on adenosine receptors, also have medicinal activity as sedatives, muscle relaxants, antipsychotics, tranquilizers, analgesics, respiratory stimulants and anti-depressants.

An important function of adenosine in the cardiovascular system is its cardioprotective action. The level of endogenous adenosine is increased in response to ischemia and hypoxia and provides protection is the cardiac tissue during and after trauma (head start). Thus, agonists of adenosine can be used as cardioprotective agents.

Adenosine modulates many aspects of kidney function, including the release of renin, the rate of glomerular filtration and renal blood flow. Compounds that are antagonists of the renal actions of adenosine, can be used as a renal protective agent. In addition, antagonists of A3and/or And2Bcan be used in the treatment of asthma and other allergic responses.

Modern information about adenosine receptors can be found, for example, in the following publications:

Bioorganic & Medicinal Chemistry, 6, 619-641 (1998),

Bioorganic & Medicinal Chemistry, 6, 707-719 (1998),

J. Med. Chem., 41, 2835-2845 (1998),

J. Med. Chem., 41, 3186-3201 (1998),

J. Med. Chem., 41, 2126-2133 (1998),

J. Med. Chem., 42, 706-721 (1999),

J. Med. Chem., 39, 1164-1171 (1996),

Arch. Pharm. Med. Chem., 332, 39-41 (1999).

Objects of the present invention are the compounds of formula I and their pharmaceutically acceptable salts individually and as pharmaceutically active compounds, their receipt of the medicinal product based on them and receive them, as well as the use of compounds of the formula I is due to the effect of the modulation of the adenosine system for the treatment or prevention of diseases, such as Alzheimer's disease, Parkinson's disease, a neuroprotective effect, schizophrenia, anxiety, pain, respiratory disorder,depression, asthma, allergic responses, hypoxia, ischaemia, seizure and abuse of drugs. In addition, the compounds of the present invention can be used as sedatives, muscle relaxants, antipsychotics, anti-epileptics, anticonvulsants and cardioprotective agents. The most preferred indications in the present invention are indications, based on antagonistic effect on receptor-a2Aand including disorders of the Central nervous system, for example the treatment or prevention of certain depressive disorders, neuroprotective action and Parkinson's disease.

The term "(ness.)alkyl"used in the text of the application, means a saturated alkyl group with straight or branched chain, containing from 1 to 6 carbon atoms, for example methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, 2-butyl, tert-butyl, etc. Preferred (ness.)alkyl groups are groups containing 1-4 carbon atoms.

The term "(ness.)alkenyl"used in the text of the application, means an unsaturated alkyl group with straight or branched chain, containing from 2 to 6 carbon atoms and at least one double bond, such as ethylene, propylene, isopropylene, n-butylene, isobutylene, 2-butylene, tert-b is a stylish, etc. Preferred (ness.)alkenylamine groups are groups containing 2-4 carbon atoms.

The term "halogen" means chlorine, iodine, fluorine and bromine.

The term "(ness.)alkoxy" means a group in which the alkyl residue has the values listed above, and which is attached via an oxygen atom.

"Acetylamino" means the group-NHC(O)CH3and "acetyl" means-C(O)CH3.

The term "pharmaceutically acceptable acid additive salts" means salts of inorganic or organic acids, such as hydrochloric acid, nitric acid, sulfuric acid, phosphoric acid, citric acid, formic acid, fumaric acid, maleic acid, acetic acid, succinic acid, tartaric acid, methanesulfonate acid, para-toluensulfonate acid, etc.

Preferred are the compounds of formula I of the present invention, in which R1means thiophenyl, a R2means phenyl not substituted or substituted with halogen or (ness.)the alkyl, for example, the following connections:

4-bromo-N-(8-methoxy-5-thiophene-2-yl[1,2,4]triazolo[1,5-a]pyridine-2-yl)benzamid,

N-(8-methoxy-5-thiophene-2-yl[1,2,4]triazolo[1,5-a]pyridine-2-yl)benzamid,

3-chloro-N-(8-methoxy-5-thiophene-2-yl[1,2,4]triazolo[1,5-a]pyridine-2-yl)benzamid,

4-chloro-N-(8-methoxy-5-thiophene-2-yl[1,2,4]triazolo[1,5-a]pyridine-2-yl)benzamide or 4-stor is l-N-(8-methoxy-5-thiophene-2-yl[1,2,4]triazolo[1,5-a]pyridine-2-yl)benzamide.

Also preferred are compounds in which R1means phenyl not substituted or substituted by a group (ness.)alkoxy, and R2means phenyl not substituted or substituted with halogen. Examples of such compounds are the following compounds:

4-fluoro-N-(8-methoxy-5-phenyl[1,2,4]triazolo[1,5-a]pyridine-2-yl)benzamid,

3-bromo-N-(8-methoxy-5-phenyl[1,2,4]triazolo[1,5-a]pyridine-2-yl)benzamid,

4-bromo-N-(8-methoxy-5-phenyl[1,2,4]triazolo[1,5-a]pyridine-2-yl)benzamide or N-[5-(3-ethoxyphenyl)-8-methoxy[1,2,4]triazolo[1,5-a]pyridine-2-yl]-4-perbenzoic.

Preferred are also the compounds of formula I of the present invention, in which R1means phenyl not substituted or substituted with halogen or (ness.)alkoxy, and R2means thiophenyl, not substituted or substituted (ness.)the alkyl, for example the following compounds:

(8-methoxy-5-phenyl[1,2,4]triazolo[1,5-a]pyridine-2-yl)amide 5-methylthiophene-2-carboxylic acid,

[5-(2-forfinal)-8-methoxy[1,2,4]triazolo[1,5-a]pyridine-2-yl]amide 5-methylthiophene-2-carboxylic acid,

[8-methoxy-5-(3-methoxyphenyl)[1,2,4]triazolo[1,5-a]pyridine-2-yl]amide 5-methylthiophene-2-carboxylic acid,

[8-methoxy-5-(4-methoxyphenyl)[1,2,4]triazolo[1,5-a]pyridine-2-yl]amide 5-methylthiophene-2-carboxylic acid,

[5-(3-ethoxyphenyl)-8-methoxy[1,2,4]triazolo[1,5-a]pyridine-2-yl]amide 5-methylthiophene-2-carboxylic acid sludge is

[5-(3-forfinal)-8-methoxy[1,2,4]triazolo[1,5-a]pyridine-2-yl]amide 5-methylthiophene-2-carboxylic acid.

Also preferred are compounds in which R1means thiophenyl, not substituted or substituted with halogen, and R2means thiophenyl, not substituted or substituted (ness.)the alkyl. Examples of such compounds are the following compounds:

(8-methoxy-5-thiophene-3-yl[1,2,4]triazolo[1,5-a]pyridine-2-yl]amide 5-methylthiophene-2-carboxylic acid, or

[5-(5-chlorothiophene-2-yl)-8-methoxy[1,2,4]triazolo[1,5-a]pyridine-2-yl]amide 5-methylthiophene-2-carboxylic acid.

These compounds of formula I and their pharmaceutically acceptable salts can be obtained well-known in the art methods, for example by the methods described below, and the method includes

a) interaction of the compounds of formula

with the compound of the formula R2COCl (III) to form compounds of formula

where R1and R2have the meanings indicated above, or

b) interaction of the compounds of formula

with KIO3with the formation of the compounds of formula

and then with the compound of the formula R1-B(OH)2(VIa) or

education connection is ormula

where R1and R2have the meanings specified above,

or

C) modifying one or more substituents R1or R2within the values specified above, and if necessary, the conversion of the compounds obtained into pharmaceutically acceptable acid additive salt.

In more detail the formation of compounds of formula I described in examples 1-51 and shown in scheme 1, where the following abbreviations are used:

DMSOthe sulfoxide
DMFdimethylformamide
DMAP4-dimethylaminopyridine
DCM4-(dicyanomethylene)-2-methyl-6-(4-dimethylaminostyryl)-
4H-Piran
THFtetrahydrofuran

R1and R2have the values specified above.

The diagram shows the method of obtaining derivatives of 8-methoxy[1,2,4]triazole[1,5-a]pyridine of the compounds of formula VII (commercial preparation). To a suspension of KOH in DMSO is added 2-amino-3-hydroxypyridine (VII) and the solution stirred. Then add methyliodide and get a connection VIII. A mixture of compound VIII and ethoxycarbonylmethylene in dioxane was stirred at room te is the temperature with the formation of compound IX. Then to a solution of hydroxylamine hydrochloride and n-ethyldiethanolamine in a mixture of methanol/ethanol added N-(3-methoxy-2-pyridinyl)-N'-carbomethoxyamino with the formation of compounds of formula X. the compound Obtained, 8-methoxy[1,2,4]triazolo[1,5-a]pyridine-2-alamid, dissolved in the compound of formula R2COCl (III) to form compounds of formula IV. The compound of formula III may be a benzoyl chloride, 4-F-benzoyl chloride, cyclohexanecarbonyl etc.

In addition, the compound of formula X can be dissolved in sulfuric acid, and then heated to approximately 100°and parts for 1 h add KIO3. Then in the resulting compound of formula X atom of iodine substituted with substituent R1at the same time as the original connection using 8-methoxy-5-iodine[1,2,4]triazolo[1,5-a]pyridine-2-ylamine, and as a reagent corresponding Bronevoy acid or ester, for example, as described in the following list, you get a compound of formula I.

Getting salt is carried out at room temperature by known methods, including specialists in this field of technology. It is as salts of inorganic acids, and salts of organic acids. Examples of such salts are hydrochloride, hydrobromide, the sulfates, itrate, the citrates, acetates, maleate, succinate, methanesulfonate, para-toluensulfonate etc.

The compounds of formula I and their pharmaceutically acceptable acid additive salts have valuable pharmacological properties. It is established that the compounds of the present invention primarily are ligands of the adenosine receptor.

The biological activity of the compounds was determined by the following method.

The binding of adenosine receptor And2Aperson

Adenosine receptor And2Aman recombinante expressed in egg cells of the Chinese hamster (Cho) using the expression system of the virus Semliki forest. Cells were collected, washed twice by centrifugation, homogenized again and washed by centrifugation. The washed precipitate containing membrane fraction, suspended in a buffer solution of Tris 50 mm (pH 7.4)containing 120 mm NaCl, 5 mm KCl, 2 mm CaCl2and 10 mm MgCl2(buffer solution). Analysis of the binding of [3H]-SCH-58261 (Dionisotti, etc., Br. J. Pharmacol., 121, 353 (1997)) was performed in 96-well tablets in the presence of 2.5 μg of membrane protein, 0.5 mg of granules SPA, covered with a Ysi-poly-L-lysine and 0.1% adelaideans in the final volume of 200 μl of buffer A. non-specific binding was determined in the presence of related compounds of xanthinuria (KHAS, 2 μm). Linking analyzed is connected to the th was determined at 10 concentrations ranging from 10 μm to 0.3 nm. All analyses were performed in repeated experiments and repeated at least twice. Analitical plates were incubated at room temperature for 1 h, centrifuged, and determined the amount of bound ligand containing radioactive label, on scintillation counter (Packard Topcount). The value of the IC50was calculated by nonlinear curve using the software, and the values of Kiwas calculated by the equation of Cheng-Prussoff.

The results of the analysis of compounds of formula I have high affinity to the receptor A2A. The table below summarises the values of specific binding compounds, characterized by the value of Kiless than 1000 nm. Preferred are compounds, the value of Kiwhich in relation to the receptor binding Aza person (hA2A), is less than 150 nm.

The compounds of formula I and pharmaceutically acceptable salts of compounds of formula I can be used as medicines, for example, in the form of pharmaceutical preparations. The pharmaceutical preparations can be administered orally by the way, for example, in the form of pills, tablets in the shell, coated tablets, hard and soft gelatine capsules, solutions, emulsions or suspensions. However, it is also effective introduction rectal method, for example, in the form of suppositories,or parenterally way for example, in the form of injection solutions.

To obtain pharmaceutical preparations of the compounds of formula I can be processed in a mixture with pharmaceutically inert, inorganic or organic carriers. As such carriers upon receipt of tablets, pills in the shell, coated tablets and hard gelatin capsules are used, for example, lactose, corn starch or its derivatives, talc, stearic acid or its salts and the like are Suitable carriers for soft gelatine capsules are, for example, vegetable oils, waxes, fats, semi-solid and liquid polyols and the like, But in the case of soft gelatin capsules, depending on the nature of the active compounds usually do not require any medium. Suitable carriers upon receipt of solutions and syrups are, for example, water, polyols, glycerol, vegetable oils, etc. are Suitable carriers for suppositories are, for example, natural or hardened oils, waxes, fats, semi-solid or liquid polyols and the like

Moreover, the pharmaceutical preparations can contain preservatives, soljubilizatory, stabilizers, wetting agents, emulsifiers, sweeteners, colorants, flavoring agents, salts for modifying the osmotic pressure, buffer substances, masking agents or antioxidants. In addition, they can contain other therapeu the automatic valuable substances.

Drugs, containing a compound of formula I or its pharmaceutically acceptable salt and a therapeutically inert carrier are also an object of the present invention. The object of the invention is also a method of obtaining these drugs, including the processing of one or more compounds of the formula I and/or their pharmaceutically acceptable acid additive salts and optionally one or more other therapeutically valuable substances in a mixture with one or more therapeutically inert carrier in the finished herbal form.

The compounds of formula I of the present invention, and their pharmaceutically acceptable salts due to the antagonistic action on adenosine receptor are used for treatment or prevention of diseases, such as Alzheimer's disease, Parkinson's disease, a neuroprotective effect, schizophrenia, anxiety, pain, respiratory disorder, depression, asthma, allergic responses, hypoxia, ischaemia, seizure and abuse of drugs. In addition, the compounds of the present invention can be used as sedatives, muscle relaxants, antipsychotics, anti-epileptics, anticonvulsants and cardioprotective agents and to obtain suitable the drugs.

The most preferred indications in the present invention are indications that include violation of the Central nervous system, for example the treatment or prevention of certain depressive States, a neuroprotective effect and Parkinson's disease.

The dose can vary within wide limits and should be adjusted to the individual requirements in each particular case. In General, when orally administered to adult patients is sufficient daily dose from about 0.01 mg to priblizitelino 1000 mg of the compounds of General formula I or the corresponding number of its farmatsevticheskii acceptable salt. The daily dose is given as a single dose and single-dose and, in addition, in case of appropriate indications, the upper limit can be exceeded.

Example 1

N-(8-Methoxy-5-phenyl[1,2,4]triazolo[1,5-a]pyridine-2-yl)basamid

a) 3-Methoxypyridine-2-ylamine

To a suspension of the 33.2 g (0,592 mol) of KOH in 80 ml of DMSO was added 15.9 g (0,144 mole) 2-amino-3-hydroxypyridine and the mixture was stirred for 90 min After 60 min was added to 9.9 ml (0,158 mole) under the conditions and the mixture was stirred at room temperature for 14 hours Then the reaction was stopped by adding 450 ml of water and was extracted with diethyl ether (8×500 ml). The combined organic layers were washed with water, dried over MgSO4and was evaporated to dryness. The remainder of perakis allisonville of ethyl acetate, when this was received of 6.99 g (56.3 mmole, 39%) indicated in the title compound as white crystals.

1H NMR (DMSO-d6, 250 MHz): δ 7,49 (dd, J15 Hz, J2the 1.4 Hz, 1H, H-4), 6,98 (dd, J17.7 Hz, J2the 1.4 Hz, 1H, H-6), 6,48 (dd, J17.7 Hz, J25 Hz, 1H, H-5), the ceiling of 5.60 (.s, 2H, NH2in ), 3.75 (s, 3H, och3).

b) N-(3-Methoxy-2-pyridinyl)-N'-carbomethoxyamino

A mixture of 8 g (64 mmole) of 3-methoxypyridine-2-ylamine and 7,29 ml (64 mmole) ethoxycarbonylmethylene (64 mmole) in 120 ml of dioxane was stirred at room temperature for 1 h, and then evaporated to dryness, thus received 16 g (62,7 mmole, 97%) indicated in the title compound as yellow crystals.

1H NMR (DMSO-d6, 250 MHz): δ 11,65 (.s, 1H, NH), 11,09 (.s, 1H, NH), 8,01 (dd, J1the 4.7 Hz, J21.3 Hz, 1H, H-4), 7,53 (dd, J17 Hz, J21.3 Hz, 1H, H-6), 7,33 (dd, J17 Hz, J2the 4.7 Hz, 1H, H-5), 4,22 (q, J 7,1 Hz, 2H, SED, of 3.33 (s, 3H, och3), of 1.26 (t, J 7,1 Hz, 3H, CH3).

in) 8-Methoxy[1,2,4]triazolo[1,5-a]pyridine-2-ylamine

To a solution of 21.8 g (313,7 mmole) of hydroxylamine hydrochloride and to 32.2 ml (188,2 mmole) of N-ethyldiethanolamine in a mixture of 130 ml of methanol/ethanol, 1:1, was added 16 g (62,7 mmole) of N-(3-methoxy-2-pyridinyl)-N'-carbomethoxybiphenyl and stirred at room temperature for 2 h and then at 60°C for 3 hours the Volatile components were removed under reduced pressure,the residue was transferred into 100 ml of water. The precipitate was washed with 25 ml of methanol/diethyl ether, 4:1, and then 25 ml of diethyl ether. After drying in high vacuum received 8 g (48.7 per mmole, 78%) indicated in the title compound in the form of crystals off-white color. MS (m/e): 163,0 (M-H, 100%).

1H NMR (DMSO-d6, 250 MHz): δ 8,13 (dd, J16,6 Hz, J21 Hz, 1H, H-5), 6,89 (dd, J17,1 Hz, J21 Hz, 1H, H-7), 6,77 (dd, J17,1 Hz, J26,6 Hz, 1H, H-5), 5,88 (users, 2H, NH2), 3,90 (s, 3H, och3).

g) 5-Iodine-8-methoxy[1,2,4]triazolo[1,5-a]pyridine-2-ylamine

A mixture of 3 g (to 18.3 mmole) of 8-methoxy[1,2,4]triazolo[1,5-a]pyridine-2-ylamine, 6 ml of water and 6 ml of sulfuric acid (97%) was heated at 100°and portions over 1 h was added 4.3 g (20.1 mmole) KIO3. The mixture was heated at 120°C for 3 h and was added 6 ml of water and 6 ml of sulfuric acid (97%). Then the mixture was cooled to 0°C, the precipitate was separated and washed with water (2×15 ml), to receive specified in the title compound in the form of beige crystals. The mother liquor was treated with Na2CO3and was extracted with DCM (5×250 ml). The combined organic layers were dried over MgSO4and was evaporated to dryness, to receive additional amounts specified in the connection header. The product was recrystallized from ethanol, to receive 2,59 g (8.9 mmole, 49%) of the final product.

1H NMR (DMSO-d6, 250 MHz): B4; 7,22 (d, J 8.2 Hz, 1H, H-7), 6,76 (d, J 8.2 Hz, 1H, H-6), 6,10 (.s, 2H, NH2), the 3.89 (s, 3H, och3).

d) 8-Methoxy-5-phenyl[1,2,4]triazolo[1,5-a]pyridine-2-ylamine

A mixture of 50 mg (0.17-mmole) 5-iodine-8-methoxy[1,2,4]triazolo[1,5-a]pyridine-2-ylamine and 46.2 mg (range 0.38 mmole) of phenylboronic acid, and 6.3 mg (0,008 mmole) of adduct dichloro[1,1'-bis(diphenylphosphino)ferrocene]palladium(II)dichloromethane and 0.3 ml of 2 M aqueous solution of Na2CO3in 1 ml of dioxane was heated at 80°C for 90 minutes Then the mixture was filtered through a small layer of silica gel and was suirable 30 ml of ethyl acetate. The filtrate was concentrated under reduced pressure, the residue was purified preparative GHUR sorbent with reversed phase (eluent: gradient of water/acetonitrile), was obtained 12 mg (29%) specified in the connection header. MS (m/e) (%): 241,3 (MN+, 100).

1H NMR (DMSO-d6, 250 MHz): δ of 7.82 (dd, J18,1 Hz, J21 Hz, 2H, phenyl), of 7.48 (m, 3H, phenyl), for 6.81 (dd, J1an 8.4 Hz, J21 Hz, 2H, H-6 and H-7), 4,53 (.s, 2H, NH2), a 4.03 (s, 3H, och3).

W) N-(8-Methoxy-5-phenyl[1,2,4]triazolo[1,5-a]pyridine-2-yl)-benzamide

A mixture of 30 mg (0.125 mmole) of 8-methoxy-5-phenyl[1,2,4]triazolo[1,5-a]pyridine-2-yl-amine, and 19.2 mg (0,137 mmole) of benzoyl chloride and 27 NEt3in 0.5 ml of dioxane was shaken at room temperature for 4 days. Then it was added 0.05 ml of formic acid and the mixture was shared by preparative obremeniaet GHUR (eluent: gra is ient water/acetonitrile), when this was received 8.6 mg (19%) specified in the connection header. MS m/e (%): 345 (MN+, 100).

1H-NMR (DMSO, 500 MHz): δ 7,95 (t, 4H, Ph), to 7.61(m, 6H, Ph), 7,30 (m, 3H, Ph/ NH), of 4.05 (s, 3H, och3).

Derivatives of [1,2,4]triazolo[1,5-a]pyridine was obtained according to the method described in example 1.

The results are shown in the following table includes examples 2-51.

Method get

1. Components 1, 2, 3 and 4 were mixed and granulated by adding purified water.

2. The granules were dried at a temperature of 50°C.

3. The pellets were crushed on the appropriate mill

4. Added component 5 and was stirred for 3 min; then extruded tablets on the appropriate tabletirujut equipment.

Method get

1. Components 1, 2, 3 were mixed in an appropriate mixer for 30 min

2. Added components 4 and 5 and was stirred for 3 minutes

3. The mixture was filled in capsules.

Derivatives of 8-methoxy[1,2,4]triazolo[1,5-a]pyridine of General formula I

where R1means phenyl, unsubstituted or substituted by one Deputy, selected from the group comprising halogen, trifluoromethyl, (ness.)alkyl, (ness.)alkoxy, acetylamino, acetyl, (ness.)alkenyl, -C(O)O-(ness.)alkyl or thio(ness.)alkyl, or thiophenyl, possibly substituted with halogen, or indolyl;

R2means phenyl, unsubstituted or substituted by one Deputy, selected from the group comprising halogen, (ness.)alkyl, halogen(ness.)alkyl or (ness.)alkoxy, or thiophenyl possibly substituted (ness.)the alkyl, and their pharmaceutically acceptable salts.

2. The compound of formula I according to claim 1, where R1means thiophenyl, and R2means phenyl, unsubstituted or substituted with halogen or (ness.)the alkyl.

3. The compound of formula I according to claim 2, in which the connection is:

4-bromo-N-(8-methoxy-5-thiophene-2-yl[1,2,4]triazolo[1,5-a]pyridine-2-yl)benzamid,

N-(8-methoxy-5-thiophene-2-yl[1,2,4]triazolo[1,5-a]pyridine-2-yl)benzamid,

3-chloro-N-(8-methoxy-5-thiophene-2-yl[1,2,4]triazolo[1,5-a]pyridine-2-yl)benzamid,

4-chloro-N-(8-methoxy-5-thiophene-2-yl[1,2,4]triazolo[1,5-a]pyridine-2-yl)benzamide or

4-ethyl-N-(8-methoxy-5-thiophene-2-yl[1,2,4]triazolo[1,5-a]pyridine-2-yl)benzamide.

4. The compound of formula I according to claim 1, where R1means phenyl, unsubstituted or substituted (ness.)alkoxy, and R2means phenyl, asamese the hydrated or substituted with halogen.

5. The compound of formula I according to claim 4, where the connection is:

4-fluoro-N-(8-methoxy-5-phenyl[1,2,4]triazolo[1,5-a]pyridine-2-yl)benzamid,

3-bromo-N-(8-methoxy-5-phenyl[1,2,4]triazolo[1,5-a]pyridine-2-yl)benzamid,

4-bromo-N-(8-methoxy-5-phenyl[1,2,4]triazolo[1,5-a]pyridine-2-yl)benzamide or

N-[5-(3-ethoxyphenyl)-8-methoxy[1,2,4]triazolo[1,5-a]pyridine-2-yl]-4-perbenzoic.

6. The compound of formula I according to claim 1, where R1means phenyl, unsubstituted or substituted with halogen or (ness.)alkoxy, and R2means thiophenyl, unsubstituted or substituted (ness.)the alkyl.

7. The compound of formula I according to claim 6, where the connection is:

(8-methoxy-5-phenyl[1,2,4]triazolo[1,5-a]pyridine-2-yl)amide 5-methylthiophene-2-carboxylic acid,

[5-(2-forfinal)-8-methoxy[1,2,4]triazolo[1,5-a]pyridine-2-yl]amide 5-methylthiophene-2-carboxylic acid,

[8-methoxy-5-(3-methoxyphenyl)[1,2,4]triazolo[1,5-a]pyridine-2-yl]amide 5-methylthiophene-2-carboxylic acid,

[8-methoxy-5-(4-methoxyphenyl)[1,2,4]triazolo[1,5-a]pyridine-2-yl]amide 5-methylthiophene-2-carboxylic acid,

[5-(3-ethoxyphenyl)-8-methoxy[1,2,4]triazolo[1,5-a]pyridine-2-yl]amide 5-methylthiophene-2-carboxylic acid, or

[5-(3-forfinal)-8-methoxy[1,2,4]triazolo[1,5-a]pyridine-2-yl]amide 5-methylthiophene-2-carboxylic acid.

8. The compound of formula I according to claim 1, where R1means thiophenyl, nez is displaced or substituted with halogen, and R2means thiophenyl, unsubstituted or substituted (ness.)the alkyl.

9. The compound of formula I of claim 8, where the connection is:

(8-methoxy-5-thiophene-3-yl[1,2,4]triazolo[1,5-a]pyridine-2-yl]amide 5-methylthiophene-2-carboxylic acid, or

[5-(5-chlorothiophene-2-yl)-8-methoxy[1,2,4]triazolo[1,5-a]pyridine-2-yl]amide 5-methylthiophene-2-carboxylic acid.

10. Pharmaceutical drug that has an antagonistic effect on adenosine receptor And2Acontaining one or more compounds of the formula I according to one of claims 1 to 9, and pharmaceutically acceptable excipients.



 

Same patents:

FIELD: organic chemistry, biochemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel derivatives of naphthyridine of the formula (I): or their salts wherein R1 means phenyl or phenyl substituted with one or two substitutes chosen from group including cyano-group, halogen atom, carboxyl, aminocarbonyl group and others; R2 means (C3-C8)-cycloalkyl substituted with carboxyl or (C1-C8)-alkoxycarbonyl. Compounds of the formula (I) and their salts possess inhibitory effect with respect to activity of phosphodiesterase isozyme 4 (PDE4) and can be used for preparing a medicinal agent in treatment of obstructive or inflammatory disease of respiratory ways.

EFFECT: valuable medicinal properties of compounds, improved method of synthesis.

8 cl, 1 tbl, 22 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention describes 8-amino-[1,2,4]triazolo-[1,5-a]pyridine-6-carboxylic acid amide of the formula (I): wherein R1 means -NR'R'' wherein R'1 and R'' represent independently of one another lower alkyl, -(CH2)n-C(O)NRaRb, -(CH2)n-pyridinyl, -(CH2)n-phenyl, -(CH2)n-CN, -(CH2)n-O-lower alkyl or -(CH2)n-(C3-C8)-cycloalkyl; or R' and R'' form in common with nitrogen atom (N) 5- or 6-membered nonaromatic ring system wherein the latter can comprise additionally one heteroatom - oxygen (O) or sulfur (S) atom and wherein indicated ring system can be unsubstituted or substituted with one or two substitutes chosen from group consisting of lower alkyl, -C(O)NRaRb or group -(CH2)n-O-lower alkyl; each Ra and Rb represents independently hydrogen atom or lower alkyl; R2 means phenyl or heteroaryl representing pyridinyl, furanyl substituted possibly with halogen atom, or lower alkyl, thiophenyl substituted possibly with lower alkyl, or thiazolyl radical, and its pharmaceutically acceptable salts also. Compounds can be used in treatment of disease associated with adenosine A2-receptors.

EFFECT: valuable medicinal properties of compounds.

12 cl, 1 tbl, 108 ex

FIELD: organic chemistry, chemical technology, pharmacy.

SUBSTANCE: invention relates to novel derivatives of urea of the general formula (I): and their pharmaceutically acceptable salts wherein A represents -CH- or nitrogen atom; R1 represents (C3-C10)-alkyl, (C3-C10)-cycloalkyl, (C3-C10)-cycloalkyl-(C1-C10)-alkyl, 6-membered nitrogen-containing heterocycle, 6-membered nitrogen-containing heterocyclyl-(C1-C10)-alkyl, phenyl, phenyl-(C1-C10)-alkyl, 5-10-membered heteroaryl or 5-10-membered heteroaryl-(C1-C10)-alkyl, and others; R2 represents hydrogen atom, (C1-C6)-alkyl, (C0-C2)-alkyl-(C3-C10)-cycloalkyl, (C0-C2)-alkylphenyl, (C3-C10)-cycloalkyl-(C0-C2)-alkyl or phenyl-(C0-C2)-alkyl; R5 represents (C1-C6)-alkyl, (C3-C10)-cycloalkyl, 6-membered nitrogen-containing heterocyclyl, and others; L1 represents -S-, -S(O)-, -S(O2)-, -C(O)-, -N(Rc)-, -CH2-, and others; L2 represents a covalent bond, -O-, -C(O)-, -OC(O)-, -N(Rc)-, and others; W represents oxygen (O) or sulfur (S) atom; Z represents -C(O)ORd wherein Rc, Rd and Re represents hydrogen atom or alkyl; Rb represents -ORe, -NO2, halogen atom, -CN, -CF, (C1-C6)-alkyl; p represents a whole number from 0 to 4. Compounds of the formula (I) and their salts possess antagonistic activity with respect to α4-integrin and can be used in medicine for inhibition or prophylaxis of cellular adhesion in patient body mediated by α4β1- and/or α4β7-integrins.

EFFECT: improved methods of synthesis, valuable medicinal properties of compounds and pharmaceutical composition.

17 cl, 2 tbl, 180 ex

FIELD: medicine.

SUBSTANCE: preparation contains chemical compound of formula (I) and new amido-substituted imidazoquinolines of formula (I).

EFFECT: enhanced effectiveness of cytokine biosynthesis.

41 cl, 23 tbl

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to imidazopyridine derivatives of the formula (I): that are inhibitors of proton pump. Invention describes compound of the formula (I) or its pharmaceutical acceptable salt wherein Het represents a 5-6-membered aromatic heterocyclic group comprising at least one atom of oxygen or sulfur and substituted with group R3 and group R4 at ortho-positions; R1 represents hydrogen atom (H), -CH3 or -CH2OH; R2 represents -CH3 or -CH2CH3; R3 and R4 are chosen independently from the following group: H, (C1-C6)-alkyl, hydroxylated (C1-C6)-alkyl; R5 and R6 are chosen independently from hydrogen atom, (C1-C6)-alkyl, hydroxylated (C1-C6)-alkyl, (C1-C6)-alkoxy-(C1-C6)-alkyl, hydroxylated (C1-C6)-alkoxy-(C1-C)-alkyl, either R5 and R6 can form morpholine or hydroxylated pyrrolidine in common with nitrogen atom to which they are bound; X represents -NH; R10 represents -CH2-. Also, invention describes intermediate compounds used for their synthesis. Invention provides preparing novel compounds possessing useful biological properties.

EFFECT: valuable medicinal properties of compounds and medicinal agents.

2 cl, 1 tbl, 23 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention describes a compound of the formula (I): wherein X means alkylene group; Y means -CO-, -CS- or -SO2-group; Z represents a simple bond or -NR5-group; R1 represents unsubstituted phenyl or phenyl substituted with halogen atom. (C1-C20)-alkyl group; R2 is chosen from -alkyl, -alkyl-O-alkyl; R3 and R4 represent alkyl; R5 represents hydrogen atom or (C1-C10)-alkyl group; Also, invention describes intermediate compounds - derivatives of imidazopyridine-4-amine, 2-phenoxypyridine and 4-phenoxypyridine. Proposed compounds and pharmaceutical compositions are able to stimulate biosynthesis of different cytokines and can be used in treatment of viral and tumor diseases.

EFFECT: valuable medicinal properties of compounds and pharmaceutical compositions.

32 cl, 1 tbl, 9 ex

FIELD: medicine.

SUBSTANCE: compound is represented by structural formula

or its pharmaceutically permissible salts, where R1 is the hydrogen atom (1), C1-8acyl(2), hydroxyl (3), halogen atom (5), C2-8acyl (3), C1-8-alcocsy (4), substituted with phenyl or C2-8acyl, substituted with NR2R3; R2R3 independently represent hydrogen atom (1) or C1-8acyl(2), X and Y each independently representing C (1), CH (2) or N (3). is (1) single or (2) double bond. is 5-7-member carbocyclic group or 5-7-member partially or fully saturated heterocyclic group defined in claim 1 of invention. A is one of A1 to A5 groups defined by claim 1 of the invention. The compounds show inhibiting properties relative to poly(ADP-ribose)polymerase are usable as prophylactic and/or curative drugs for treating ischemic diseases (in brain, spinal cord, heart, digestive tract, skeletal muscle, eye retina, e.t.c.), inflammatory diseases (intestinal inflammation, disseminated sclerosis, arthritis, e.t.c.), neurodegenerative disorders (extrapyramidal disorder, Alzheimer disease, muscle dystrophy, cerebrospinal canal stenosis in lumbar segment of the vertebral column, e.t.c.), diabetes, stroke, cerebral injury, hepatic insufficiency, hyperalgesia, e.t.c. The compounds are also of use in struggling against retroviruses (HIV and others), as sensitizing agents for treating cancer cases and immunodepressant agents.

EFFECT: enhanced effectiveness of treatment.

19 cl, 90 tbl

FIELD: organic chemistry, herbicides, agriculture.

SUBSTANCE: invention describes a herbicide against weeds resistant to sulfonylurea-base herbicide and comprising compound of the formula (I):

wherein Q represents condensed heterocyclic group of the formula (Q1), (Q3), (Q4) given in the invention description; X represents lower alkyl or lower alkoxyl group; Y represents lower alkoxyl group. Invention describes compound of the formula (II):

wherein R1 represents halogen atom or optionally halogenated lower alkyl group; R2 represents hydrogen atom; R3 represents (C2-C4)-alkyl group or lower cycloalkyl group; X represents lower alkyl group or lower alkoxyl group; Y represents lower alkoxyl group. Also, invention describes herbicides comprising compounds of the formula (II) and a method for control of weeds resistant to sulfonylurea-base herbicide. Method involves applying herbicide comprising compound of the formula (I) or compound of the formula (II). Herbicide is used for control of weeds resistant to sulfonylurea-base herbicide in rice-paddy fields.

EFFECT: valuable properties of herbicides.

10 cl, 8 tbl, 69 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to triheterocyclic compound of the formula (I): wherein X represents carbon atom; Y represents carbon or nitrogen atom; W represents carbon or nitrogen atom; U represents -CR2, and Z represents -CR2 or nitrogen atom; ring A represents (C5-C6)-cycloalkyl ring or 5-membered heterocyclic ring comprising one nitrogen, oxygen or sulfur atom; R1 represents alkyl, alkenyl, alkynyl, -NR4R5, -OR6 and others; R3 represents phenyl ring substituted with 1-3 substitutes or pyridyl or 1,3-dioxoindanyl ring substituted with 1-2 substitutes, and its pharmaceutically acceptable salts and pharmaceutical composition containing thereof as an active component. Also, invention relates to derivatives of pyrazolopyrimidine and derivatives of pyrrolopyrimidine. Compounds of the formula (I) show antagonistic activity with respect to corticotropin-releasing factor receptors. The compound can be used in treatment and/or prophylaxis of depression, anxiety state, disorders in food intake, post-traumatic stress, ulcerous disease, irritable bowel syndrome, Alzheimer's disease, abuse in drugs using or alcoholic syndrome dependence.

EFFECT: valuable medicinal properties of compounds and pharmaceutical agent.

7 cl, 1 dwg, 24 ex

FIELD: pharmacology, medicine.

SUBSTANCE: invention relates to new mercaptoacetylamide derivatives, which represents angiotensine converting enzyme and neutral endopeptidase inhibitors and useful in treatment of cardiovascular condition. More particularly invention relates to derivatives of formula I , wherein R1 represents hydrogen or acyl; wherein R2 represents hydrogen or biphenylmethyl; { represents -(CH2)n (n = 1, integer); B1 and B2 are independently hydrogen; or pharmaceutically acceptable salts or stereomers thereof. Method for production of compounds of formula I and formula II, pharmaceutical composition on the base of formula I, method for production thereof and method for treatment of cardiovascular condition.

EFFECT: new derivatives having value biological properties.

14 cl, 3 tbl, 4 ex, 1 dwg

FIELD: organic chemistry, medicine.

SUBSTANCE: invention relates to a novel using to compounds of the general formula (I): . Also, invention relates to preparing a medicinal agent used for modulating sodium channels and, in particular, in treatment of pain (for example, neuropathic pain), epilepsy, neurodegenerative states and bipolar states.

EFFECT: valuable medicinal properties of compounds.

10 cl, 18 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to a novel compound, namely, (+)-1-(3,4-dichlorophenyl)-3-azabicyclo[3.1.0]hexane or its pharmaceutically acceptable (-)-enantiomer-free salts. This compounds is able to bind with norepinephrine and serotonin carriers that provides their using as components of pharmaceutical composition used in treatment of depression, anxiety state or nutrient disorder.

EFFECT: valuable medicinal properties of compound and pharmaceutical composition.

16 cl, 2 tbl, 4 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention describes a novel compound 4-(2-butylamino)-2,7-dimethyl-8-(2-methyl-6-methoxypyrid-3-yl)[1,5-a]-1,3,5-triazine of the formula (I):

, its steroisomeric forms or pharmaceutically acceptable salts, pharmaceutical composition comprising thereof and its using for preparing pharmaceutical composition used in treatment of anxiety in mammals.

EFFECT: valuable medicinal property of compound and pharmaceutical composition.

7 cl, 2 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to triheterocyclic compound of the formula (I): wherein X represents carbon atom; Y represents carbon or nitrogen atom; W represents carbon or nitrogen atom; U represents -CR2, and Z represents -CR2 or nitrogen atom; ring A represents (C5-C6)-cycloalkyl ring or 5-membered heterocyclic ring comprising one nitrogen, oxygen or sulfur atom; R1 represents alkyl, alkenyl, alkynyl, -NR4R5, -OR6 and others; R3 represents phenyl ring substituted with 1-3 substitutes or pyridyl or 1,3-dioxoindanyl ring substituted with 1-2 substitutes, and its pharmaceutically acceptable salts and pharmaceutical composition containing thereof as an active component. Also, invention relates to derivatives of pyrazolopyrimidine and derivatives of pyrrolopyrimidine. Compounds of the formula (I) show antagonistic activity with respect to corticotropin-releasing factor receptors. The compound can be used in treatment and/or prophylaxis of depression, anxiety state, disorders in food intake, post-traumatic stress, ulcerous disease, irritable bowel syndrome, Alzheimer's disease, abuse in drugs using or alcoholic syndrome dependence.

EFFECT: valuable medicinal properties of compounds and pharmaceutical agent.

7 cl, 1 dwg, 24 ex

FIELD: medicine, cardiology, psychiatry.

SUBSTANCE: one should carry out traditional therapy of myocardial infarction and, additionally, prescribe perorally pyrasidol at the dosage of 25 mg twice daily for 21 d in combination with eglonyl at 1 ml (50 mg) once daily intramuscularly for 10 d. The present innovation enables to decrease the tension of regulatory systems due to decreasing sympathetic impacts and activation of parasympathetic department of autonomic nervous system.

EFFECT: higher efficiency of therapy.

1 ex, 3 tbl

FIELD: medicine, in particular clinical pharmacology for treatment of bipolar disorder.

SUBSTANCE: claimed method includes administration of therapeutically effective amount of enantiomere of formula Ib ,namely from 0.01 to 100 mg/kg per day to subject.

EFFECT: agent for effective arresting bipolar disorder of type I and type II, cyclothymic disorder, bipolar depression, acute folie, stroke, associated with bipolar disorder, etc.

5 cl, 2 ex, 2 tbl

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to pharmaceutically acceptable 2-ethyl-6-methyl-3-oxypyridine salts with organic carboxylic acids of the general formula: (1-V1): wherein R means -CH2OH (I); R means -CH2-COOH (II); R means -(CH2)3-COOH (III); R means -(CH2)4-COOH (IV); R means -CH(OH)-CH(OH)-COOH (V); R means -CH(NH2)-CH2-COOH (VI) possessing with anxiolytic, antidepressive, antihypoxic, anti-amnestic and anti-oxidative activity and showing decreased toxicity. Also, invention relates to a method for preparing salts and pharmaceutical composition.

EFFECT: improved preparing method, valuable medicinal properties of compounds and pharmaceutical composition.

3 cl, 10 tbl, 10 ex

FIELD: medicine, pharmacy.

SUBSTANCE: invention relates to new medicinal agents for parenteral using based on an antidepressant agent pirlindole salts. Agent comprises 2,3,3a,4,5,6-hexahydro-8-methyl-1H-pyrazino[3,2,1-j,k]carbazole (pirlindole) sulfonate salts as an active substance, such as methane sulfonate or benzene sulfonate. The composition for intravenous or intramuscular injection comprises additionally citric acid and water taken in the definite ratios. Invention provides preparing an agent possessing good tolerance, low toxicity and resistance in storage.

EFFECT: improved and valuable medicinal and pharmaceutical properties of agent.

2 cl, 1 tbl, 4 ex

FIELD: pharmacy.

SUBSTANCE: invention proposes pharmaceutical compositions consisting of multiple particles with sustained-release of serotonin reuptake selective inhibitor (SRSI) with membrane cover comprising ammonium-methacrylate copolymer, or compositions comprising SRSI particles mixture, or compositions comprising SRSI particles mixture in form of sustained-release of SRSI, Also, invention relates to method for treatment of depression involving administration of these compositions. In particular, SRSI represents fluoxetine, fluvoxamine, sertraline or their salt. Proposed compositions provide a less index of fluctuations that reflects lower values of maximal concentrations of substance in plasma blood after multiple administrations, safety and good tolerance also.

EFFECT: improved medicinal and pharmaceutical properties of compositions.

11 cl, 5 dwg, 26 tbl, 6 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to arylsulfonyl derivatives of the formula (I): , wherein Ar means naphthyl or phenyl substituted optionally with halogen atom or (C1-C6)-alkoxy-group; R1 means (C1-C6)-alkyl; R2 means hydrogen atom or (C1-C6)-alkyl, or their pharmaceutically acceptable salts or solvates. Proposed compounds show affinity to HT6 receptors. Also, the claim describes pharmaceutical compositions comprising indicated compounds, their using as therapeutic agents and a method for their preparing. Compounds can be useful in treatment of some disturbances in the central nervous system (CNS).

EFFECT: improved preparing method, valuable medicinal properties of compounds and composition.

12 cl, 1 tbl, 12 ex

FIELD: medicine, pharmacy, medicinal agents.

SUBSTANCE: invention relates to aripiprazol pharmaceutical solutions used in oral using and designated for treatment of schizophrenia. Proposed agent comprises aripiprazol, pharmaceutically useful system of solvents, one or more taste-improving/masking agents and one or more acids chosen from group consisting of lactic, acetic, tartaric and citric acid and wherein pH of proposed pharmaceutical solution is from 2.5 to 4.5. Invention provides dissolving difficultly soluble medicinal agent and to compensate aripiprazol bitter taste and to obtain stable solution of this substance.

EFFECT: improved properties of agent.

17 cl, 2 tbl, 3 ex

Up!