Non-competitive nicotinic receptor antagonists

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to new compounds of formula I or their pharmaceutically acceptable salts possessing the properties of a neuronal nicotinic receptor antagonist. The compounds can find application for treating a disease or condition, which represents irritable bowel syndrome with diarrhoea (IBS-D), overactive bladder (OAB), nicotine addiction, smoking cessation, depression, major depressive disorder, or hypertension mediated by neuronal nicotinic receptor activity. In formula I: each of R1 and R2 individually represents H, C1-6alkyl, or R1 and R2 are bound to a nitrogen atom to which they are attached, to form 3-8-merous ring; R3 represents H, C1-6alkyl; each of R4, R5, R6 and R7 individually represents H, C1-6alkyl; L1 represents a linker specified in a group consisting of CR8R9, CR8R9CR10R11 and O; L2 represents a linker specified in a group consisting of CH2, CH2CH2, CH2CH2CH2 or CH2CH2CH2CH2; each of R8, R9, R10 and R11 individually represents hydrogen or C1-6alkyl, and a dashed line represents an optional double bond.

EFFECT: producing salts possessing the properties of the neuronal nicotinic receptor antagonist.

15 cl, 1 tbl, 9 ex

 



 

Same patents:

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to the pharmaceutical industry and concerns new derivatives of the antitumour antibiotic oligomycin A and a method for preparing them by regioselective [3+2]dipolar cycloconnection of an azido group of 33-deoxy-33-azidooligomycin A(1) to monosubstituted alkines. The new derivatives of the antibiotic oligomycin A described by formula: , wherein R represents 1,4-disubstituted 1,2,3-triazoles, namely a. - (phenyl-triazol-1-yl), b. - (4-carboxy-triazol-1-yl), c. - (4-4-methoxycarbonyl-triazol-1-yl), d. - (4-dimethylaminoethylamidocarboxytriazol-1-yl) possess manifested antitumour activity and higher solubility as compared to the initial oligomycin A.

EFFECT: preparing the new derivatives of the antitumour antibiotic.

3 cl, 4 dwg, 3 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to a compound of general formula (I): wherein m and n independently represent 0 or 1; G and E represent oxygen, R1 and R2 together with a carbon atom whereto attached form a heterocycle including one or two heteroatoms specified in oxygen, sulphur, -S(O)-, -S(O)2-, -N=, -N(R5)-; one or more carbon atoms in the above heterocycle are optionally substituted by one or more identical or different substitutes specified among the substitutes R4; R3 represents alkoxy or halogenoxy; R4 represents hydrogen, alkyl or halogen; R5 represents hydrogen, alkyl carbonyl, alkoxy carbonyl or alkyl sulphonyl; X represents a bond, -CH2- or -NH-; A represents phenyl, pyridyl, pyrazynyl or quinolyl optionally substituted by one or more identical or different substitutes specified among the substitutes R4; or pharmaceutically acceptable salts, hydrates, N-oxides or salvates thereof.

EFFECT: invention also refers to the pharmaceutical composition of the above compounds as the phosphodiesterase PDE4 inhibitor for treating, eg skin diseases.

19 cl, 2 tbl, 32 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel antibiotic oligomycin A derivatives, having anti-tumour activity and low toxicity, of formula: , where R is a methanesulphonic acid (OSO3CH3) residue or an azide group (N3) and synthesis method and use thereof.

EFFECT: obtaining novel antibiotic oligomycin A derivatives.

3 cl, 1 dwg, 1 tbl, 4 ex

FIELD: organic chemistry, pharmacology.

SUBSTANCE: invention relates to new aromatic diketone derivatives of formula I

(R4, R5, R6, and R7 are independently H, OH, X-alkyl, wherein X represents oxygen; K is group of formula II

or III

;

L is group of formula IV

;

or K and L together form group of formula VI ,

wherein R1 and R3 are independently H or alkyl; R2 is H or alkyl; X1-X7 are independently O, NH; and ring "cyclus" together with carbon atom labeled with letters c and d represents anthraquinone, hydroquinone or phenyl, optionally substituted with one or more hydroxyl, alkoxyl, or alkyl groups), as well as pharmaceutically accepts salts thereof, ethers, esters, tautomers, stereomers and mixtures in any ratio. Derivatives of present invention are glucose-6-phosphatetranslocase inhibitors. Also disclosed are method for production of derivatives, pharmaceutical composition containing the same, and uses thereof as drugs, in particular for treatment of diabetes mellitus.

EFFECT: new compounds and pharmaceutical composition for treatment of diabetes mellitus.

20 cl, 4 tbl, 6 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to 6'-aryl-2'-(2-hydroxyphenyl) - 11',11'-dimethyl- 3', 4, 4', 13'-tetraoxospiro[2,5-cyclohexadien-1,9' - (7' - oxa - 2',12' -diazatetracyclo[6.5.1.01,5.08,2]-tetradec-5'-en]-14'-carboxylates of general formula (IIIa,b) III: Ar=Ph (a), C6H4Me-n (b), and method for preparing them.

EFFECT: preparing the compounds to be used as analgesic agents.

2 cl, 2 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention describes a crystalline hydrate of camptothecin esters, namely the crystalline hydrates of camptothecin aliphatic esters, a pharmaceutical composition containing the crystalline hydrates of camptothecin aliphatic esters for treating cancer or malignant tumours, as well as a method for treating cancer or malignant tumour.

EFFECT: what is prepared and described is the new crystalline form of the hydrate of camptothecin aliphatic ester possessing low toxicity and good absorbability in a living body.

19 cl, 5 ex, 10 tbl, 5 dwg

FIELD: chemistry.

SUBSTANCE: invention relates to method of staurosporin purification, which includes obtaining staurosporin solution in first solvent, where first solvent represents benzyl ancohol; introduction into solution of purified staurosporin seeding in second solvent; and separation of product. Also described is method of obtaining N-benzoylstaurosporin, including reaction of staurosporin with benzoic anhydride with formation of solution; introduction into solution of amorphous N-benzoylstaurosporin; and separation of product.

EFFECT: method improvement.

3 cl, 3 dwg, 1 tbl, 16 ex

FIELD: chemistry.

SUBSTANCE: invention relates to cytotoxic compounds of directed action and methods for therapeutic use thereof in treating neoplasm and other diseases.

EFFECT: high treatment efficiency.

9 cl, 12 tbl, 31 ex, 3 dwg

FIELD: medicine.

SUBSTANCE: invention refers to new 5-substituted derivatives of thiocamptothecin of general formula 1: , wherein: R represents hydrogen, -N3; R1 hydrogen, ethyl, group -CH=N-O-C(CH3)3; R2 represents hydrogen, -CH2N(CH3)2; R3 represents hydrogen, hydroxyl, group , to their pharmaceutically acceptable salts, enantiomers, diastereoisomers and related mixtures.

EFFECT: higher anticancer activity of the compound.

10 cl, 3 tbl, 34 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new derivatives of 5-substituted camptothecin of formula 1 wherein R represents F, R1 represents hydrogen; R2 represents hydrogen; and R3 represents hydrogen; its pharmaceutically acceptable salts, diastereoisomers and appropriate mixtures which show anticancer activity.

EFFECT: invention refers to a method for preparing of these compounds, using them as anticancer drugs, and to pharmaceutical compositions containing them.

6 cl, 2 tbl, 22 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing topotecan - a cytostatic agent from a group of camptothecins, which is used as a topoisomerase I inhibitor

.

The method involves: a) reducing camptothecin (1) to 1,2,6,7-tetrahydro-20(S)-camptothecin (3) using 2,6-dimethyl-3,5-dicarbmethoxy-1,4-dihydropyridine (2) in the presence of trifluoroacetic acid in chloroform medium at 60°C; b) oxidising 1,2,6,7-tetrahydro-20(S)-camptothecin (3) with iodobenzene diacetate (4) to 10-hydroxy-20(S)-camptothecin (5) in an acetic acid-water medium at 20-25°C; c) obtaining 9-[(dimethylamino)methyl] 10-hydroxy-20(S)-camptothecin (7) reacting 10-hydroxy-20(S)-camptothecin (5) with bis(dimethylamino)methane (6) in acetic acid medium at 20-25°C; d) extracting topotecan - 9-[(dimethylamino)methyl] 10-hydroxy-20(S)-camptothecin hydrochloride via crystallisation from acetone.

EFFECT: invention enables to obtain an end product using a simple method with sufficiently high output.

4 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: there are described new camptothecin derivatives, i.e. 4,5-dihydrotriazolyl [5,4-c]16a-deoxocamptothecin and triazolyl[5,4-c]16a-deoxocamptothecin showing anticancer activity, a pharmaceutical composition containing them and applying them as anticancer drugs.

EFFECT: preparing the anticancer pharmaceutical composition.

5 cl, 11 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a method for preparing aliphatic camptothecin ester that involves a reaction of a parent compound of camptothecin with at least one alkylating agent and at least one acid, in which said parent compound of camptothecin represents 20(S)-camptothecin and said alkylating agent has formula R1COX1 or (R1CO)2O, where R1 represents CH3, C2H5; C3H7; C4H9; C6H13; C8H17 or CH=CHCH3; X1 represents halogenide; and where said acid represents sulphuric acid; and in which the parent compound of camptothecin represents 9-nitro-camptothecin and said alkylating agent has formula R1COX1 or (R1CO)2O, where R1 represents C2H5; C3H7; C4H9; C6H13 or i-C3H7; X1 represents halogenide; and where said acid represents sulphuric acid. Also, the invention refers to crystalline camptothecin-20-propionate which can find application as an antineoplastic drug.

EFFECT: method provides preparing high-yield products.

4 cl, 1 tbl, 2 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: what is described a new compound representing (2R)-5'-[5-(morpholin-4-ylmethyl)-3-furyl]-3'H-spiro[4-azabicyclo[2.2.2]octane-2,2'-furo[2,3-b]pyridine and a pharmaceutical composition binding with alpha-7 nicotinic receptors and containing them which can find application in medicine.

EFFECT: preparing the new pharmaceutical composition.

2 cl, 16 ex

FIELD: biotechnology.

SUBSTANCE: invention relates to new symmetrical diimines based on camphor of general formula 1a-f, which are inhibitors of influenza virus reproduction (strain A/California/07/09 (H1N1) pdm09). In the general formula 1a-f The compounds along with pronounced antiviral activity against the said influenza virus have low toxicity.

EFFECT: chemotherapeutic index exceeds that of the known reference preparations three or more times.

1 tbl, 8 ex

FIELD: chemistry.

SUBSTANCE: in adamantane amino-derivatives of general formula (1), R=OH, R1=R2=R3=H, R4=C2H5, X=Cl, n=1 (I); R=Br, R1=R2=R3=H, R4=C2H5, X=Br, n=1 (II); R=OH, R1=R2=H, R3+R4=-CH2CH2CH2CH2-, X=Cl, n=1 (III); R=Br, R1=R2=H, R3+R4=-CH2CH2CH2CH2-, X=Br, n=1 (IV); R=OH, R1=R2=CH3, R3=R4=H, X=CI, n=1 (V); R=CH3, R1=-CH2OH, R2=R3=R4=H, X=Cl, n=1 (VI).

EFFECT: higher antiviral activity of derivatives towards influenza virus.

1 cl, 1 tbl, 9 ex

FIELD: organic chemistry.

SUBSTANCE: claimed method includes reduction of 2-nitro-3-phenyl-Δ5-norcamphene with active hydrogen obtaining by reaction of aluminum containing in nickel-aluminum alloy with potassium hydroxide, wherein 1 N potassium hydroxide solution and powdered nickel-aluminum alloy are added to 2-nitro-3-phenyl-Δ5-norcamphene solution in tetrahydrofurane followed by treatment thereof with ethanol in presence of skeletal nickel catalyst forming in reduction step to produce N-3-phenyl-2-norcamphanyl)-N-etnylamine followed interaction thereof with hydrogen chloride and isolation of target product. Compound of present invention is useful in medicine as active ingredient of preparations with tonic action.

EFFECT: new method for production of N-(3-phenyl-2-norcamphanyl)-N-etnylamine hydrochloride.

1 cl, 1 ex

FIELD: chemistry.

SUBSTANCE: invention relates to method of obtaining hydrochlorides of adamantane amines, including 1-aminoadamantane hydrochlorides or 3,5-dimethyl-1-aminoadamantane, which are pharmaceutical substance of medications "Midantan" and "AcatinpolMemantine". Method consists in oxidation of cage hydrocarbon, selected from adamantane or methyl-substituted adamantanes, with fuming nitric acid in molar ratio 1:7-13.3 respectively, in presence of glacial acetic acid in molar ratio 1:1-3.25 counted per initial substrate at room temperature. After that, acetone cyanohydrin is added in molar ratio 1:3.5-10.4 and water in molar ratio 1:75.1-102.9 counted per initial substrate, with further heating with boiling of reaction mass for 1-3 h, neutralisation of obtained reaction mass and addition of hydrochloric acid.

EFFECT: method in accordance with invention is simpler in comparison with previously known methods, because it does not require application of hard-to-obtain reagents, eliminates stage of thermal decomposition of intermediate product, makes it possible to increase environmental friendliness, reduce amount of wastewater and is more fire- and explosion-safe.

12 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds of formula , wherein A means a six-merous aryl radical or a five-merous heteroaryl radical which contains one heteroatom specified in oxygen and sulphur; one or more hydrogen atoms in the above aryl or heteroaryl radicals can be substituted by substituting groups R1 which are independently specified in a group consisting of: F, Cl, Br, I, (C1-C10)-alkyl-, (C1-C10)-alkoxy-, -NR13R14; B means a radical with mono- or condensed bicyclic rings specified in a group consisting of: six-ten-merous aryl radicals, five-ten-merous heteroaryl radicals and nine-fourteen-merous cycloheteroalkylaryl radicals, wherein cycloheteroalkyl links can be saturated or partially unsaturated, while the heterocyclic groups can contain one or more heteroatoms specified in a group consisting of nitrogen, oxygen and sulphur, one or more hydrogen atoms in the radical groups B can be substituted by substituting groups R5 (as specified in the patent claim), L means a covalent bond, X means the group -O-, R2 is absent or means one or more substitutes specified in F and (C1-C4)-alkyl radical; R3 and R4 independently mean (C1-C10)-alkyl, (C3-C14)-cycloalkyl, (C4-C20)-cycloalkylalkyl, (C2-C19)-cycloheteroalkyl, (C3-C19)-cycloheteroalkylalkyl, (C6-C10)-aryl, (C7-C20)-arylalkyl, (C1-C9)-heteroaryl, (C2-C19)-heteroarylalkyl radicals, or R3 and R4 together with nitrogen attached whereto can form a four-ten-merous saturated, unsaturated or partially unsaturated heterocyclic compound which can additionally contain one or more heteroatoms among -O-, -S(O)n-, =N- and -NR8-; other radicals are such as specified in the patient claim. Also, the invention refers to using the compound of formula I for preparing a drug.

EFFECT: compounds of formula (I) as Na+/H+ metabolism inhibitors NHE3.

22 cl, 27 dwg, 1 tbl, 756 ex

FIELD: chemistry.

SUBSTANCE: in formula 1 , X denotes a negative charge which is localised on a fullerene skeleton, a chlorine atom bonded to a carbon skeleton or a hydrogen atom; the NR1R2 moiety denotes an amine residue, where R1 and R2 are hydrogen atoms or linear or branched alkyl radicals (CmH2m+1; n=1-20) that are substituted with protonated (NH3+) or unprotonated (NH2) amine groups, or a piperazine residue of general formula 1c-1 , where R, R'1, R'2, R'3 and R'4 are hydrogen atoms or linear or branched alkyl (CmH2m+1; n=1-20) radicals, as well as residues of aliphatic alcohols -(CH2)nOH, ethers -(CH2)nOR'5, thiols -(CH2)nSH, acids -(CH2)nCOOH, esters thereof -(CH2)nCOOR'5 or amides -(CH2)nCONR'5R'6, for which n=0-20, R'5 and R'6 are hydrogen atoms or linear alkyl (CmH2m+1; n=1-20) radicals.

EFFECT: stronger or prolonged antibacterial action.

2 cl, 2 dwg, 2 tbl, 3 ex

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