Diazabicyclic aryl derivatives used as modulators of cholinergic receptors

FIELD: medicine.

SUBSTANCE: there described are diazabicyclic aryl derivatives of general formula I , their enantiomers or any mixture of those enantiomers, or their pharmaceutically acceptable salts, where radical values A, L, B and n are given in the description, and pharmaceutical composition containing the above diazabicyclic aryl derivatives.

EFFECT: new compounds represent cholinergic ligands of nicotinic receptors of acetylcholine and modulators of receptors and carrying agents of monoamines, and can be used for treatment of diseases and illnesses related to cholinergic system of central nervous system and periphery nervous system, which are related to activity of muscles, endocrine diseases, inflammatory diseases, and neurodegenerative diseases.

12 cl, 2 ex, 1 tbl

 

The text descriptions are presented in facsimile form.

1. Diazabicyclo aryl derivative represented by the formula I

or its pharmaceutically acceptable salt, where
n is 1, 2 or 3, and
A represents a phenyl group, thiadiazolyl, pyridinyl or pyridazinyl;
B is a
the group is phenyl or pyridinyl, which may be substituted by substituents selected from the group consisting of alkyl, cycloalkyl, hydroxy, alkoxy, halogeno, cyano, amino, nitro and-NH(CO)R””, where
R”” represents hydrogen, alkyl or cycloalkyl; and
L is a
linking group selected from-O-, -S-, -S-CH2-, -SO-, -C≡C-, -NHCO-, -NHCONH -, or-NH(SO2)-.

2. Diazabicyclo aryl derivative according to claim 1, where n is 1 or 2.

3. Diazabicyclo aryl derivative according to claim 1, where In represents a phenyl group or pyridinyl, which may be substituted alkoxy, halogeno, cyano, amino, nitro and-NH(CO)R ' ” wherein R”” represents hydrogen or alkyl.

4. Diazabicyclo aryl derivative according to claim 1, where
n = 2;
Rather it represents a phenyl, thiadiazolyl, pyridinyl or pyridazinyl;
Represents a phenyl group or pyridinyl, possibly substituted by substituents selected from the group consisting of alkyl is, cycloalkyl, hydroxy, alkoxy, halogeno, cyano, nitro and a group-NH(CO)-alkyl; and
L represents-O-, -S-, -S-CH2-, -SO-, -C≡C-, -NHCO-, -NHCONH -, or-NH(SO2)-.

5. Diazabicyclo aryl derivative according to claim 4, where
n = 2;
Rather it represents a phenyl;
Represents a phenyl, possibly substituted by substituents selected from the group consisting of alkyl, cycloalkyl, hydroxy, alkoxy, halogeno, cyano, amino, nitro and a group-NH(CO)-alkyl; and
L represents-O-, -S-, -S-CH2-, -SO-, -C≡C-, -NHCO-, -NHCONH -, or-NH(SO2)-.

6. Diazabicyclo aryl derivative according to claim 5, which is a
N-[4-(l,4-diaza-bicyclo[3.2.2]non-4-yl)-phenyl]-benzamide;
1-[4-(1,4-diaza-bicyclo[3.2.2]non-4-yl)-phenyl]-3-phenyl-urea;
N-[4-(1,4-diaza-bicyclo[3.2.2]non-4-yl)-phenyl]-2-nitro-benzamide;
N-[4-(1,4-diaza-bicyclo[3.2.2]non-4-yl)-phenyl]-3-nitro-benzamide;
N-[4-(1,4-diaza-bicyclo[3.2.2]non-4-yl)-phenyl]-4-nitro-benzamide;
2-Amino-N-[4-(1,4-diaza-bicyclo[3.2.2]non-4-yl)-phenyl]-benzamide;
3-Amino-N-[4-(1,4-diaza-bicyclo[3.2.2]non-4-yl)-phenyl]-benzamide;
4-Amino-N-[4-(1,4-diaza-bicyclo[3.2.2]non-4-yl)-phenyl]-benzamide;
2-Acetylamino-N-[4-(1,4-diaza-bicyclo[3.2.2]non-4-yl)-phenyl]-benzamide;
3-Acetylamino-N-[4-(1,4-diaza-bicyclo[3.2.2]non-4-yl)-phenyl]-benzamide;
4-Acetylamino-N-[4-(1,4-diaza-bicyclo[3.2.2]non-4-yl)-phenyl]-benzamide;
N-[4-(1,4-diaza-bicyclo[3.2.2]non-4-yl)-phenyl]-3-methoxy-benzamide;
N-[4-1,4-diaza-bicyclo[3.2.2]non-4-yl)-phenyl]-benzosulfimide;
N-[4-(1,4-diaza-bicyclo[3.2.2]non-4-yl)-phenyl]-4-methoxy-benzamide;
N-[4-(1,4-diaza-bicyclo[3.2.2]non-4-yl)-phenyl]-3-cyano-benzamide;
N-[4-(1,4-diaza-bicyclo[3.2.2]non-4-yl)-phenyl]-4-cyano-benzamide;
N-[4-(1,4-diaza-bicyclo[3.2.2]non-4-yl)-phenyl]-3-fluoro-benzamide;
N-[4-(1,4-diaza-bicyclo[3.2.2]non-4-yl)-phenyl]-4-fluoro-benzamide;
N-[4-(1,4-diaza-bicyclo[3.2.2]non-4-yl)-phenyl]-2-fluoro-benzamide;
N-[4-(1,4-diaza-bicyclo[3.2.2]non-4-yl)-phenyl]-4-nitro-benzosulfimide or
4-Amino-N-[4-(1,4-diaza-bicyclo[3.2.2]non-4-yl)-phenyl]-benzosulfimide
or their pharmaceutically acceptable salt.

7. Diazabicyclo aryl derivative according to claim 1, where
n = 2;
But thiadiazolyl, pyridinyl or pyridazinyl;
Represents a phenyl or pyridinyl, possibly substituted by substituents selected from the group consisting of alkyl, cycloalkyl, hydroxy, alkoxy, halogeno, cyano, amino, nitro and a group-NH(CO)-alkyl; and
L represents-O-, -S-, -S-CH2-, -SO-, -C≡C-, -NHCO-, -NHCONH -, or-NH(SO2)-.

8. Diazabicyclo aryl derivative according to claim 7, where a is thiadiazolyl.

9. Diazabicyclo aryl derivative of claim 8, which is 4-(5-Benzylmethyl-[1.3.4]-thiadiazole-3-yl)-1,4-diaza-bicyclo[3.2.2]nonan or its pharmaceutically acceptable salt.

10. Diazabicyclo aryl derivative according to claim 7, where a represents pyridine is or pyridazinyl.

11. Diazabicyclo aryl derivative of claim 10, which is a
4-(6-Phenylethynyl-pyridazin-3-yl)-1,4-diaza-bicyclo[3.2.2]nonan;
4-[6-(4-Amino-phenylethynyl)-pyridazin-3-yl]-1,4-diaza-bicyclo[3.2.2]nonan;
4-[6-(3-Fluoro-phenylethynyl)-pyridazin-3-yl]-1,4-diaza-bicyclo[3.2.2]nonan;
4-[6-(4-Methoxy-phenylethynyl)-pyridazin-3-yl]-1,4-diaza-bicyclo[3.2.2]nonan;
4-[6-(3-Pyridinylamino)-pyridazin-3-yl]-1,4-diaza-bicyclo[3.2.2]nonan;
4-(6-Phenylsulfanyl-pyridin-3-yl)-1,4-diaza-bicyclo[3.2.2]nonan;
4-(6-Phenylsulfanyl-pyridin-3-yl)-1,4-diaza-bicyclo[3.2.2]nonan;
4-(6-Phenoxy-pyridazin-3-yl)-1,4-diaza-bicyclo [3.2.2] nonan;
4-[6-(1,4-diaza-bicyclo[3.2.2]non-4-yl)-pyridin-3-yl]-3-(2-nitro-phenyl)-urea 1-N-oxide;
N-[6-(1,4-diaza-bicyclo[3.2.2]non-4-yl)-pyridin-3-yl]-benzamide;
1-[6-(1,4-diaza-bicyclo[3.2.2]non-4-yl)-pyridin-3-yl]-3-phenyl-urea;
N-[6-(1,4-diaza-bicyclo[3.2.2]non-4-yl)-pyridin-3-yl]-4-nitro-benzamide;
N-[6-(1,4-diaza-bicyclo[3.2.2]non-4-yl)-pyridin-3-yl]-3-nitro-benzamide;
4-Amino-N-[6-(1,4-diaza-bicyclo[3.2.2]non-4-yl)-pyridin-3-yl]-benzamide;
3-Amino-N-[6-(1,4-diaza-bicyclo[3.2.2]non-4-yl)-pyridin-3-yl]-benzamide;
4-Acetylamino-N-[6-(1,4-diaza-bicyclo[3.2.2]non-4-yl)-pyridin-3-yl]-benzamide;
3-Acetylamino-N-[6-(1,4-diaza-bicyclo[3.2.2]non-4-yl)-pyridin-3-yl]-benzamide;
N-[6-(1,4-diaza-bicyclo[3.2.2]non-4-yl)-pyridin-3-yl]-3-methoxy-benzamide;
N-[6-(1,4-diaza-bicyclo[3.2.2]non-4-yl)-pyridin-3-yl]-3-cyano-benzamide is whether
N-[6-(1,4-diaza-bicyclo[3.2.2]non-4-yl)-pyridin-3-yl]-4-cyano-benzamide
or their pharmaceutically acceptable salt.

12. A pharmaceutical composition comprising a therapeutically effective amount diazabicyclo aryl derivative according to any one of claims 1 to 11 or its pharmaceutically acceptable salt of joining together at least one pharmaceutically acceptable carrier or diluent, for the treatment, prevention or relief of disease, disorder or condition that is sensitive to modulation of cholinergic receptors and/or monoamine receptors.



 

Same patents:

FIELD: medicine.

SUBSTANCE: there are described new diazabicyclic aryl derivatives of general formula (I), where A', A", L and B, n possess the values as specified in the description which are cholinergic ligands to nicotinic acetylcholine receptors, as well as a based pharmaceutical composition. Owing to their pharmacological profile, the compound according to the invention, can be effective in treating such various diseases or disorders, as those associated with the cholinergic system of central nervous system (CNS), peripheral nervous system (PNS), as those associated with plain muscle contraction, endocrine diseases or disorders, neurodegenerative diseases or disorders, diseases or disorders involving inflammation, pain and abstinence symptoms caused by termination of abusing the chemical substances.

EFFECT: effective with regard to various diseases.

16 cl, 3 ex, 1 tbl

FIELD: chemistry.

SUBSTANCE: claimed invention relates to quinobenzoxazin analogues with general formula (1) where V represents H, halo-, or NR1R2; NH2, or NR1-(CR12)n-NR3R4; A represents H, fluoro-, or NR12; Z represents O, S, NR1 or CH2; U represents NR1R2; X represents NR1R2 or halo-; n=1-6; where in NR1R2, R1 and R2 can form 5-7-member heterocyclic ring which is optionally substituted and has 1-2 heteroatoms, selected from group consisting of N, O and S; R1 represents H or C1-6alkyl; R2 represents C1-10alkyl optionally including one or more non-adjacent heteroatoms N or O and is optionally substituted with if necessary substituted 3-6-member carbocyclic or 5-14-member heterocyclic ring; or R2 is 5-14-member heterocyclic ring, which has 1-2 heteroatoms, selected from group consisting of N, O or S, 6-member aryl or 5-7member heteroaryl ring, which contains 1-3 heteroatoms, selected from group consisting of N, O and S, each of which can be, if necessary, substituted; R3 represents H or C1-6alkyl; R4 represents H, C1-6alkyl, optionally substituted with 3-6 carbocyclic or 5-14-member heterocyclic ring, or 6-member aryl, R4 and R3, if necessary, can form optionally 5-7-member substituted heterocyclic ring, which contains 1-2 heteroatoms selected from N and O; W represents substituent, such as described in i.1 of invention formula, where Q, Q1, Q2, and Q3 represents independently CH or N; Y represents independently O or CH; R5 represents substituent in any position of closed ring in form of H or OR2; on condition that U is not morpholinyl or 2,4-difluoroaniline, when X represents F or pyrrolidinyl, A is F, Z represents O, and W represents phenylene; each obligatorily substituted fragment being substituted with one or more halogen, C1-6-alkoxy, amino, carbamate, C1-10alkyl, C2-10alkenyl, each of which is optionally substituted with halogen, =O, 6-member aryl or one or more heteroatom, selected from N and O; 6-member aryl, 3-6-member carbocyclic ring or 5-7-member heterocyclic ring containing 1-2 heteroatoms, selected from group, consisting of N and O; or its pharmaceutically acceptable salts. Invention also relates to pharmaceutical composition based on formula (1) compound and to method of treatment of proliferative cell diseases using formula (1) compounds.

EFFECT: obtaining novel quinobenzoxazin analogues possessing useful biological properties.

48 cl, 3 tbl, 50 ex

FIELD: chemistry.

SUBSTANCE: invention claims compound of the general formula (I) , where R is hydrogen atom or vinyl group; n is 1, X is a group of the formula CH or nitrogen atom, R1 is either phenyl or naphthyl group, or cyclohexyl group, or heteroaryl group, R2 is either hydrogen atom or one or more substitutes selected out of halogen atoms and trifluoromethyl, alkyl, alkoxyl phenyloxy, hydroxyl groups or group of the general formula -NR4R5, SO2NR4R5, or group of the formula -OCF2O-, each of R4 and R5 groups is hydrogen atom or alkyl group; and method of obtaining compound of the general formula (I), medicine, pharmaceutical composition. Compounds display special effect as specific inhibitors of glycine GlyT1 and/or GlyT2 transmitters and thus are applied in treatment of various diseases.

EFFECT: obtaining compounds with high specific inhibition effect.

13 cl, 2 tbl, 5 ex

FIELD: chemistry.

SUBSTANCE: derivatives of 7-aryl-3,9-diazabicyclo(3.3.1)non-6-ene of general formula I , general formula I, where X and W or both represent -CH-, or one of them represents -CH-, and the other -N. V represents -A-(CH2)s-, -(CH2)s-A-, -A-(CH2)v-B- or -CH2-A-(CH2)3-B-; A and B represent-O- U -phenyl, possibly 1-3 substituted with halogen, alkyl, alkoxy, CF3, CF3O - or alkylcarbonyl, or pyridyl, monosubstituted with cyanogroup. T represents -CONR1-, -(CH2)pOCO- or -(CH2)pN(R1)CO- Q-alkylene; M - hydrogen, phenyl, possibly substituted, benzo[1,3]dioxol, possibly substituted, or pyridyl; L represents -R3, -COR3, -COOR3, -CONR2R3 or -SO2R3; R1 - hydrogen, alkyl, C3-7 cycloalkyl, pyrrolidinyl, benzo[b]thienyl, chinoxalinyl, phenylalkyl, thienylalkyl or tetrazolylalkyl, possibly substituted. m=1, n=0 or m=0, n=1, p - integer 1-4, s - integer 2-5, v - integer 2-4, optically pure enantiomers, mixtures of enantiomers, pharmaceutically acceptable salts and complexes with solvents, possessing activity of phenin inhibitors.

EFFECT: efficient application in medicine for treatment of cardio-vascular diseases and renal failure.

8 cl, 743 ex

FIELD: chemistry.

SUBSTANCE: description is given of new diazabicyclic aryl derivatives, with general formula I: its enantiomers, or mixture of enantiomers, or its adjoining pharmaceutical salt, where X and Y independently represent CR2, CR3 or N, where R2 is hydrogen, C1-6alkyl or halogen; and R3 is hydrogen or halogen; and R1 is hydrogen or halogen, CF3, NO2 or phenyl, possibly substituted, group with formula phenyl-Z-(C1-6alkyl)m-, phenyl -C≡C- or pyridyl -Z-(C1-6alkyl)m-, where m equals 0 or 1; Z - O or S, where phenyl and pyridyl are possibly substituted, or R1 and R3 , together with carbon atoms to which they are bonded, form a benzocondensed aromatic carbocyclic ring, which can be substituted. The new compounds are cholinergic ligands of nicotinic acetylcholine receptors.

EFFECT: compounds can be useful for treating such diseases or disorders related to the cholinergic system of the central nervous system, peripheral nervous system etc.

11 cl, 3 ex, 1 tbl

FIELD: chemistry, pharmacology.

SUBSTANCE: invention relates to new crystalline form II of hydrated (±)-4-amino-5-chloro-2-methoxy-N-(1-aza-bicyclo[3.3.1]non-4-yl)benzamide hydrochloride, including 2 moles water to 1 mole (±)-4-amino-5-chloro-2-methoxy-N-(1-aza-bicyclo[3.3.1]non-4-yl)benzamide hydrochloride, the form II content being equal 75% and more; the above form II of hydrated (±)-4-amino-5-chloro-2-methoxy-N-(1-aza-bicyclo[3,3,1]non-4-yl)benzamide hydrochloride has one or more optional properties, as follows: a) form II infrared spectrum include characteristic peak at 835±1.5 cm-1; b) X-ray pattern obtained on the above form powder is essentially corresponds to image Fig. 21; and c) water content rates 8.3% to 9.8%. The invention relates also to the form II ofhydrated (±)-4-amino-5-chloro-2-methoxy-N-(1-aza-bicyclo[3.3.1]non-4-yl)benzamide hydrochloride production methods, to the form II of hydrated (±)-4-amino-5-chloro-2-methoxy-N-(1-aza-bicyclo[3.3.1]non-4-yl)benzamide hydrochloride, and the form II of hydrated (±)-4-amino-5-chloro-2-methoxy-N-(1-aza-bicyclo[3.3.1]non-4-yl)benzamide hydrochloride identification method, as well as to pharmaceutical composition and treatment method for gastrointestinal motility impairment related disorders.

EFFECT: composition has improved properties for medical applications.

22 cl, 1 ex, 11 tbl, 22 dwg

FIELD: chemistry.

SUBSTANCE: invention concerns new derivatives of 1- and 7-[ω-(benzhydryl-4-piperazinyl-1)alkyl]-3-alkyloxantines of the general formulae I and II, including their pharmaceutically acceptable salts and/or salt hydrates, the derivatives showing antihistaminic and antiallergenic effect. In the general formulae I and II : R = H, Me, CH2Ph; R1 = Me, "н" - C4H9; n = 0-3; X = H, OH, OCOCH2CH2COOH; Y = Y1 = H, Cl, F; on the condition that R and R1 are not both methyl. Compounds of the invention feature high antihistaminic and antiallergenic activity. E.g., 7-[4-(benzhydryl-4-piperazinyl-1)butyl]-3-methyloxantine dihydrochloride surpasses most efficient antihistaminic and antiallergenic medications, such as cetirizine, loratadine and azelastine, in activity and lasting effect.

EFFECT: obtaining a compound with high antihistaminic and antiallergenic activity.

2 cl, 3 tbl, 8 ex

FIELD: chemistry.

SUBSTANCE: invention concerns new N,N'-substituted 3,7-diazabicyclo[3.3.1]nonanes of the general formula 1: (HY), where HY is hereinafter a pharmacologically acceptable acid; E is , R1 is H, low-grade alkyl, C1-C10alkoxy; R2 is generally represented by the general formulae (1.1a) , (1.2a) , (1.3a) , (1.4a) , where L is CHR11, ; R11 is H, NH2; R15 is H, low-grade alkyl, C1-C10alkoxy; R19, R19', R20 and R20' can be equal or different, and each is independently H, low-grade alkyl, C1- C10alkoxy; R24 and R25 can be equal or different, and each is independently H, low-grade alkyl, C1- C10alkoxy; R3 and R3' can be equal or different, and each is independently H, low-grade alkyl, C1- C10alkoxy; R4 and R4' can be equal or different, and each is independently H, low-grade alkyl, C1- C10alkoxy; X is a group of the general formula: (CH2)m-Z, where m=0, while Z is acetyl, or X is a valence link. Compounds I are capable of AMPA receptor activity modulation and hence can be applied in pharmaceutical compositions.

EFFECT: obtaining compound capable of AMPA receptor activity modulation.

12 cl, 2 dgw, 2 tbl, 11 ex

FIELD: chemistry.

SUBSTANCE: invention concerns malonamide derivatives of the formulae (IA) or (IB) , and pharmaceutically acceptable acid additive salts of them, where R1, R1',(R2)1,2,3, R3, R4, R14, L, and are such as described in this invention. Also the invention concerns a medicine with inhibition effect on γ-secretase, which can be applied in treatment of Alzheimer's disease.

EFFECT: obtaining new malonamide derivatives with beneficial biological properties.

17 cl, 188 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel derivatives of 1,4-diazabicycloalkane of the formula (IV): or its pharmaceutically acceptable addition salt wherein Ar represents carbocyclic aromatic (aryl) group or heterocyclic aromatic (heteroaryl) group that represents 5-6-membered ring comprising one nitrogen, sulfur or oxygen atom as a heteroatom and wherein aromatic group can be substituted with one substitute chosen from group consisting of (C1-C6)-alkoxy, halogen atom, -CF3, phenyl and benzyl. Also, invention relates to a pharmaceutical composition possessing inhibitory effect on nicotine acetylcholine receptors and containing the effective amount of compound of the formula (IV) or its pharmaceutically acceptable addition salt in combination with at least one pharmaceutically acceptable carrier or diluting agent. Invention provides derivatives of 1,4-diazabicycloalkane possessing inhibitory activity with respect to nicotine acetylcholine receptors.

EFFECT: valuable medicinal and pharmacological properties of compounds.

10 cl, 3 ex

FIELD: chemistry.

SUBSTANCE: invention relates to levodop prodrugs, their stereoisomers, enantiomers or pharmaceutically acceptable salts and based on them pharmaceutical composition for ensuring slowed levodop release, as well as to versions of their application and methods of obtaining them, compounds can be applied for treatment or prevention of diseases in which levodop application is indicated. In general formula (I): , Q is selected from X-CO-; X is selected from -O- and -NH-; n equals integer number from 2 to 4; each R1 and R2 is independently selected from hydrogen, -OH, C1-4alkyl and substituted C1-4alkyl, where substituting group is -OH; R3 and R4 represent hydrogen; R5 is selected from hydrogen, C1-4alkyl, phenyl, substituted phenyl, where each substituting group is independently selected from C1-6alcoxy, C1-6alkyl, halogen and -OH; C3-8cycloalkyl, pyridyl, substituted pyridyl, where each substituting group is independently selected from C1-6alkyl and C1-6alcoxy; on condition that formula (I) compound is not a derivative of 1,3-dihexadecanoylpropane-1,2,3-triol.

EFFECT: elaboration of pharmaceutical composition for ensuring slowed levodop release.

48 cl, 4 dwg, 32 ex

FIELD: chemistry, medicine.

SUBSTANCE: in the general formula (I): X is oxygen atom; R1 is C1-10-alkyl , substituted if necessary by phenyl or thienyl group; or R1 is C3-7-cycloalkyl, thienyl, pyridinyl; the thienyl groups can be substituted if necessary by 1-2 C1-3-alkyl groups; phenyl can be substituted if necessary by 1-2 halogen atoms; R2 is C1-6-alkyl; or R2 is C3-7-cycloalkyl, phenyl or pyridinyl; phenyl if necessary can be substituted by one or more halogen atoms or by the CN, C1-3-alkyl, C1-3-alkoxyl, C1-3-fluoroalkyl groups; R3 is C1-6-alkyl; R4 is hydrogen atom or C1-6-alkyl; R5 and R5' are independently of each other the hydrogen atom, hydroxyl; or R5 and R5' form together the oxo-group; n is integer value in the range from 0 to 3; R6 is independently of each other hydrogen atom, halogen atom, C1-3-alkyl, C1-3-alkoxyl.

EFFECT: compounds of present invention can find application as pharmaceutical for pathology treatment where the inhibitor of β-amiloyd peptide β-A4 is useful.

8 cl, 1 tbl, 7 ex

FIELD: pharmacy.

SUBSTANCE: application of the (-)-didesmethylsibutramine or its pharmaceutically acceptable salts, solvate or clathrate for preparation of the pharmaceutical for Parkinson's disease treatment is claimed.

EFFECT: invention provides enhancing of the motion activity and release of Parkinsonism symptoms.

5 cl, 3 tbl, 15 ex

FIELD: chemistry.

SUBSTANCE: invention refers to imidazoline derivatives having CB1-antagonist activity of general formula where: R1 and R2 independently stand for phenyl which can be substituted with 1-2 substitutes Y being identical and represent chlorine, bromine, fluorine, iodine, X stands for one subgroup or , where: R3 stands for hydrogen atom or linear C1-3 alkyl group, R4 stands for C3-8 cycloalkyl or C5-10, and said groups can contain one atom N, R7 represents benzyl or phenyl group, and specified groups can be substituted in aromatic ring by 1 substitute Y, where Y is evaluated as specified above being either identical, or different, or R7 stands for C1-8dialkylaminogroup, R8 represents hydrogen atom, R9 represents hydrogen atom and their salt. Additionally, the invention concerns a pharmaceutical composition based on compound of formula I, and to its application for therapy of diseases caused by canabiod neurotransmission.

EFFECT: new compounds possess useful biological activity.

9 cl, 1 tbl, 3 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to new nitroxide compounds with formula I: where one of A, B and D represents N-O and others represent CR6; R1 represents alkyl, containing 1 to 4 carbon atoms, which is branched or straight and which is unsubstituted or substituted once or several times with a halogen; R2 represents alkyl, containing 1 to 12 carbon atoms, which is branched or straight and which is unsubstituted or substituted once or several times with a halogen; cycloalkylalkylk, containing 3 to 10 carbon atoms, which is unsubstituted or substituted once or several times with oxo, aryl, containing 6 to 14 carbon atoms, which is unsubstituted or substituted once or several times with OCF3; or a heterocyclic group, which is saturated, partially saturated or unsaturated, with 5 to 10 atoms in the ring, where at least 1 atom in the ring is an atom of N, O, or S; R3 represents cycloalkyl, containing 3 to 10 carbon atoms, which is unsubstituted once or several times with oxo, aryl, containing from 6 to 14 carbon atoms or which is unsubstituted or substituted once or several times with OCF3; or heteroaryl, with 5 to 10 atoms in the ring, in which at least 1 atom in the ring is a heteroatom; R represents H or alkyl, containing 1 to 4 carbon atoms. The invention also relates to pharmaceutically used salts of these compounds, pharmaceutical compositions containing these compounds, method of inhibiting PDE4 enzyme and to methods treatment using these compounds.

EFFECT: new compounds with useful biological properties.

62 cl, 6 ex

FIELD: medicine.

SUBSTANCE: according to the invention pharmaceutical composition contains carbostyril derivative and serotonin reuptake inhibitor in pharmaceutically acceptable carrier. Carbostyril derivative is aripiprazole. Serotonin reuptake inhibitor can include fluoxetine, duloxetine, venlafaxine, milnaciprane, cytalopram, fluvoxamine, paroxetine, sertraline or escitalopram. According to the invention, the pharmaceutical composition can be used for treatment of phrenopathy patients, particularly suffering from depression or major depressive disorder.

EFFECT: according to the invention, the composition is characterised with synergetic action and can be applied in relatively small amounts, possesses lower by-effects and satisfactory safety characteristics.

36 cl, 8 dwg, 9 ex, 3 tbl

Comt inhibitors // 2354655

FIELD: chemistry.

SUBSTANCE: invention refers to new compounds of formula I where R1 stands for H, CN, halogen, -COR2, -S(O)xR2, C1-C12alkyl, C2-C12alkenyl, C3-C8dicloalkyl, aryl group, heteroaryl group standing for 5- or 6-merous aromatic mono- or bicyclic heterocyclic group with 1-2 heteroatoms, chosen of N or S, C3-C8cycloalkyl-(C1-C3)alkyl or group aril-(C1-C3)alkyl; alkyl, alkenyl, cycloalkyl, aryl and heteroaryl groups can be optionally substituted with halogen, C1-C6alkyl, group-COR2; R2 stands for -N(R3,R3'), C1-C6alkyl, C3-C8cycloalkyl, aryl, heteroaryl which stands for 5- or 6-merous aromatic mono- or bicyclic heterocyclic group with 1-2 heteroatoms chosen of N, C3-C8cycloalkyl-(C1-C3) alkyl or aril-(C1-C3)alkyl; C1-C6alkyl, C3-C8cycloalkyl, aryl, heteroaryl can be optionally substituted with halogen, C1-C6alkyl; R3 and R3' independently stands for hydrogen or (C1-C3)alkyl; x stands for 0, 1 or 2; and also to their esters, hydrolyzed in physiological environment, and to their pharmaceutically acceptable salts. The invention also concerns a medical product.

EFFECT: production of new biologically active compounds active as COMT inhibitor.

17 cl, 19 ex, 1 tbl

FIELD: chemistry.

SUBSTANCE: invention refers to 1,2,4,5-tetrasubstituted imidazole derivatives of general formula (I) , where R1 represents chlorine, bromine, fluorine or hydrogen atom, R2 represents chlorine or bromine atom, A represents nitrogen atom or group CH, X represents sulphur atom or sulphoxide (S=O) group, or sulphonic (SO2) group, Y represents hydrogen atom or methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl group, Z represents CH group, n represents number 1,2 or 3, and pharmacologically acceptable salts of compounds. Besides, the invention concerns a pharmaceutical composition based on the compound of general formula (I), to the compounds of general formulas and and to application of compounds of general formula (I).

EFFECT: new imidazole derivatives being selective modulators of cannabinoid receptors CB1 with high selectivity.

12 cl, 1 tbl, 4 ex

FIELD: pharmacology.

SUBSTANCE: claimed invention relates to novel application of lignan compounds represented by formula I, given in description. In particular claimed invention relates to pharmaceutical composition for treatment or prevention of brain disease, which contains lignan compound, represented by formula I or Myristica fragrans extract as active ingredient, as well as method and application for treatment or prevention of brain disease with application of lignan compound. Lignan compound represented by formula I possesses anti-oxidative, protective for brain cells and anti-inflammatory effect.

EFFECT: lignan compound will be useful for treatment or prevention of brain diseases.

14 cl, 16 dwg, 2 tbl

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to neurology and enables to treat Parkinson's disease. Method involves as follows. The baseline Parkinson's disease therapy is combined with oral introduction of antioxidant carnosine during 30 days as dosed 1.5 g daily.

EFFECT: introduction of carnosine as described above allows for reduced dopaminergic neuron injuries caused by oxidative stress ensured by higher superoxide dismutase activity.

1 ex, 1 tbl, 3 dwg

FIELD: medicine.

SUBSTANCE: there are described new diazabicyclic aryl derivatives of general formula (I), where A', A", L and B, n possess the values as specified in the description which are cholinergic ligands to nicotinic acetylcholine receptors, as well as a based pharmaceutical composition. Owing to their pharmacological profile, the compound according to the invention, can be effective in treating such various diseases or disorders, as those associated with the cholinergic system of central nervous system (CNS), peripheral nervous system (PNS), as those associated with plain muscle contraction, endocrine diseases or disorders, neurodegenerative diseases or disorders, diseases or disorders involving inflammation, pain and abstinence symptoms caused by termination of abusing the chemical substances.

EFFECT: effective with regard to various diseases.

16 cl, 3 ex, 1 tbl

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