Diaminopyrimidines as p2x3 receptor antagonists

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new compounds of formula (I) and to their pharmaceutically acceptable salts exhibiting P2X3 receptor antagonist activity. In formula (I), X represents -O-; Y represents -NRdRe where one of radicals Rd and Re means hydrogen, and the other means hydrogen; C1-C12alkyl; C5-C7cycloalkyl; C5-C7cycloalky-C1-C12alkyl; hydroxy-C1-C12alkyl; acetyl; aminocarbonyloxy- C1-C12alkyl or heterocyclyl representing a 6-members saturated ring containing heteroatom S substituted by two oxo groups; D represents optional oxygen; R1 represents isopropyl; R2 represents hydrogen; R5 represents hydrogen or C1-C12alkyl; R4 means hydrogen; C1-C12alkyl; halogen; halogen- C1-C12alkyl; C1-C12alkoxy; hydroxy; halogen- C1-C12alkoxy; nitro; amino; hydroxy- C1-C12alkyl; C1-C12alkoxyalkyl; hydroxy- C1-C12alkoxy; C1-C12alkylsulphonyl; cyano; heteroaryl representing a 5-members aromatic ring containing one, two or three heteroatoms selected from O, S and N which can be optionally substituted by a thio group, C1-C12alkyl or C1-C12alkylsulphonyl; heterocyclyl representing a 6-members saturated ring containing two heteroatoms N, one of which is substituted C1-C12alkylsulphonyl; -(CH2)m-(Z)n-(CO)-Rf or -(CH2)m-(Z)n-SO2-(NRg)n-Rf where each m and n independently represents 0 or 1, Z means NR8, Rf means C1-C12alkyl, hydroxy, amino or hydroxy- C1-C12alkyl, and Rg means hydrogen; R3 represents methoxy; R6 represents hydrogen; and one of radicals R7 and R8 represents hydrogen, and the other represents hydrogen, acetyl or phenyl.

EFFECT: also, the invention refers to a pharmaceutical composition and to an application of the compound of formula (I) for preparing a drug.

8 cl, 3 tbl, 70 ex

 

The text descriptions are given in facsimile form.

1. The compound of formula (I):

or its pharmaceutically acceptable salt,
where X represents-O-;
Y is-NRdRewhere one of the radicals Rd and Rerepresents hydrogen and the other represents hydrogen; C1-C12alkyl; C5-C7cycloalkyl; C5-C7cycloalkyl-C1-C12alkyl; hydroxy-C1-C12alkyl; acetyl; aminocarboxylate-C1-C12alkyl or heterocyclyl, which represents a 6-membered saturated ring containing a heteroatom S, substituted with two exography;
D represents an optionally present oxygen;
R1represents isopropyl;
R2represents hydrogen;
R5represents hydrogen or C1-C12alkyl;
R4represents hydrogen; C1-C12alkyl; halogen; halogen-C1-C12alkyl, C1-C12alkoxy; hydroxy; halogen-C1-C12alkoxy; nitro; amino; hydroxy-C1-C12alkyl; C1-C12alkoxyalkyl; hydroxy-C1-C12alkoxy; C1-C12alkylsulfonyl; cyano; heteroaryl, which is a 5-membered aromatic ring containing one, two or three heteroatoms selected from O, S and N, which optionally may be substituted by tigraphy,1-C12the alkyl or C1-C12alkylsulfonyl; tetrazolyl, heterocyclyl, which represents a 6-membered saturated ring containing two gets is of rotoma N, one of which is substituted With1-C12alkylsulfonyl; -(CH2)m-(Z)n-(CO)-Rfor -(CH2)m-(Z)n-SO2-(NRg)n-Rfwhere m and n each independently represents 0 or 1, Z represents NRg, Rfrepresents a C1-C12alkyl, hydroxy, amino or hydroxy-C1-C12alkyl, and Rgrepresents hydrogen;
R3represents methoxy;
R6represents hydrogen; and
one of the radicals R7and R8represents hydrogen and the other represents hydrogen, acetyl or phenyl.

2. The compound according to claim 1, where the specified compound has the formula (II):

in which:
X represents-O-;
R1represents isopropyl;
R3represents methoxy;
R4represents hydrogen; C1-C12alkyl; amino; halogen; halogen-C1-C12alkyl; C1-C12alkoxy; hydroxy; halogen-C1-C12alkoxy; nitro; hydroxy-C1-C12alkyl; C1-C12alkoxyalkyl; hydroxy-C1-C12alkoxy; C1-C12alkylsulfonyl; cyano; heteroaryl, which is a 5-membered aromatic ring containing one, two or three heteroatoms selected from O, S and N, which is the optional is tion can be replaced by tigraphy, With1-C12the alkyl or C1-C12alkylsulfonyl; heterocyclyl, which represents a 6-membered saturated ring containing two heteroatoms N, one of which is substituted With1-C12alkylsulfonyl; -(CH2)m-(Z)n-(CO)-Rfor -(CH2)m-(Z)n-SO2-(NRg)n-Rfwhere type each independently represents 0 or 1, Z represents NRg, Rfrepresents a C1-C12alkyl, hydroxy, amino or hydroxy-C1-C12alkyl, and Rgrepresents hydrogen;
one of the radicals R7and R8represents hydrogen and the other represents:
the hydrogen, acetyl or phenyl; and
one of the radicals Rdand Rerepresents hydrogen and the other represents hydrogen; C1-C12alkyl; C5-C7cycloalkyl; C5-C7cycloalkyl-C1-C12alkyl; hydroxy-C1-C12alkyl; acetyl; aminocarboxylate-C1-C12alkyl or heterocyclyl, which represents a 6-membered saturated ring containing a heteroatom S, substituted with two exography.

3. The compound according to claim 1, selected from the group including
5-(2-isopropyl-4,5-dimethoxyphenoxy)pyrimidine-2,4-diamine,
5-(5-bromo-2-isopropyl-4-methoxyphenoxy)pyrimidine-2,4-diamine,
5-(5-chloro-2-and propyl-4-methoxyphenoxy)pyrimidine-2,4-diamine,
5-(2-isopropyl-4-methoxy-5-methylphenoxy)pyrimidine-2,4-diamine,
5-(5-chloro-2-isopropyl-4-methoxyphenoxy)-N*2*-isopropylpyrimidine-2,4-diamine,
N*2*-isopropyl-5-(2-isopropyl-4,5-dimethoxyphenoxy)pyrimidine-2,4-diamine,
N-[4-amino-5-(2-isopropyl-4,5-dimethoxyphenoxy)pyrimidine-2-yl]acetamide", she
3-[4-amino-5-(5-chloro-2-isopropyl-4-methoxyphenoxy)pyrimidine-2-ylamino]pentane-1,5-diol,
2-[4-amino-5-(5-chloro-2-isopropyl-4-methoxyphenoxy)pyrimidine-2-yl-amino]butane-1-ol,
1-[5-(2,4-diaminopirimidina-5-yloxy)-4-isopropyl-2-methoxyphenyl]-Etalon,
5-[5-(1H-imidazol-2-yl)-2-isopropyl-4-methoxyphenoxy]pyrimidine-2,4-diamine,
5-(2,4-diaminopirimidina-5-yloxy)-4-isopropyl-2-methoxybenzamide,
5-(2,4-diaminopirimidina-5-yloxy)-4-isopropyl-2-methoxybenzoic acid,
5-[2-isopropyl-4-methoxy-5-(1H-tetrazol-5-yl)phenoxy]pyrimidine-2,4-diamine,
5-(2,4-diaminopirimidina-5-yloxy)-4-isopropyl-2-methoxybenzonitrile,
[5-(2,4-diaminopirimidina-5-yloxy)-4-isopropyl-2-methoxyphenyl]urea,
5-(5-amino-2-isopropyl-4-methoxyphenoxy)pyrimidine-2,4-diamine,
N-[5-(2,4-diaminopirimidina-5-yloxy)-4-isopropyl-2-methoxyphenyl]acetamide", she
5-(2-isopropyl-4-methoxyphenoxy)pyrimidine-2,4-diamine,
5-(2-isopropyl-5-methanesulfonyl-4-methoxyphenoxy)pyrimidine-2,4-diamine,
5-(2-isopropyl-4-methoxy-5-methylphenoxy)-N*4*-phenylpyrimidine-2,4-diamine,
5-(5-chloro-2-isopropyl-4-methoxyphenoxy)-N*2*-(1,1-dioxohexane-1-lambda*6*-tio the Iran-4-yl)pyrimidine-2,4-diamine,
2-[4-amino-5-(5-chloro-2-isopropyl-4-methoxyphenoxy)pyrimidine-2-ylamino]propyl ether methylcarbamyl acid,
2-[4-amino-5-(5-chloro-2-isopropyl-4-methoxyphenoxy)pyrimidine-2-ylamino]-(R)propan-1-ol,
5-(5-chloro-2-isopropyl-4-methoxyphenoxy)-N2-(1,1-dioxohexane-1λ6-thiopyran-4-yl)pyrimidine-2,4-diamine,
5-(5-iodine-2-isopropyl-4-methoxyphenoxy)pyrimidine-2,4-diamine,
5-(2,4-diaminopirimidina-5-yloxy)-4-isopropyl-2-methoxybenzenesulfonamide,
3-[4-amino-5-(5-bromo-2-isopropyl-4-methoxyphenoxy)pyrimidine-2-ylamino]pentane-1,5-diol,
5-(5-iodine-2-isopropyl-4-methoxyphenoxy)-1-hydroxy-pyrimidine-2,4-diamine,
5-(2-isopropyl-4-methoxy-5-pyrazole-1-elfenix)pyrimidine-2,4-diamine,
5-[2-isopropyl-4-methoxy-5-(3-methylpyrazole-1-yl)phenoxy]pyrimidine-2,4-diamine,
5-(2-isopropyl-4-methoxy-5-oxazol-2-elfenix)pyrimidine-2,4-diamine,
5-(2-isopropyl-4-methoxy-5-triptoreline)pyrimidine-2,4-diamine,
5-(2-isopropyl-4-methoxy-5-thiazol-4-elfenix)pyrimidine-2,4-diamine,
5-(2-isopropyl-4-methoxy-5-thiophene-3-elfenix)pyrimidine-2,4-diamine,
(R)-2-[4-amino-5-(2-isopropyl-5-methanesulfonyl-4-methoxyphenoxy)pyrimidine-2-ylamino]butane-1-ol,
5-[5-(4,5-dihydrooxazolo-2-yl)-2-isopropyl-4-methoxyphenoxy]pyrimidine-2,4-diamine,
5-(2-isopropyl-5-methanesulfonyl-4-methoxyphenoxy)-N2-(2,2,2-Cryptor-ethyl)pyrimidine-2,4-diamine,
5-[2-isopropyl-4-methoxy-5-(1-methyl-1H-imidazol-2-yl)phenoxy]pyrimidine-2,4-d is Amin,
5-[2-isopropyl-4-methoxy-5-(2H-pyrazole-3-yl)phenoxy]pyrimidine-2,4-diamine,
5-(5-imidazol-1-yl-2-isopropyl-4-methoxyphenoxy)pyrimidine-2,4-diamine,
N2-isopropyl-5-(2-isopropyl-5-methanesulfonyl-4-methoxyphenoxy)pyrimidine-2,4-diamine,
5-(4-amino-2-Ethylenediamine-5-yloxy)-4-isopropyl-2-methoxybenzamide,
2-[4-amino-5-(2-isopropyl-5-methanesulfonyl-4-methoxyphenoxy)pyrimidine-2-ylamino]ethanol,
5-[2-isopropyl-4-methoxy-5-(2-methylthiazole-4-yl)phenoxy]pyrimidine-2,4-diamine,
5-(2-isopropyl-4-methoxy-5-[1,2,3]triazole-1-elfenix)pyrimidine-2,4-diamine,
5-(5-furan-2-yl-2-isopropyl-4-methoxyphenoxy)pyrimidine-2,4-diamine,
5-[5-(3,5-dimethylpyrazol-1-yl)-2-isopropyl-4-methoxyphenoxy]pyrimidine-2,4-diamine,
N2-ethyl-5-(2-isopropyl-5-methanesulfonyl-4-methoxyphenoxy)pyrimidine-2,4-diamine,
N2-isobutyl-5-(2-isopropyl-5-methanesulfonyl-4-methoxyphenoxy)-pyrimidine-2,4-diamine,
5-(2-isopropyl-5-isoxazol-5-yl-4-methoxyphenoxy)pyrimidine-2,4-diamine,
5-(2-isopropyl-4-methoxy-5-[1,2,4]oxadiazol-3-elfenix)pyrimidine-2,4-diamine,
1-[5-(2,4-diaminopirimidina-5-yloxy)-4-isopropyl-2-methoxyphenyl]ethanol,
5-(2,5-aminobutiramida 4 methoxyphenoxy)pyrimidine-2,4-diamine,
5-[2-isopropyl-4-methoxy-5-(1-methoxyethyl)phenoxy]pyrimidine-2,4-diamine,
5-(2-isopropyl-4-methoxy-5-oxazol-4-elfenix)pyrimidine-2,4-diamine,
5-(2-isopropyl-4-methoxy-5-thiazol-2-elfenix)pyrimidine-2,4-diamine,
5-(5-furan-3-yl-2-isopropyl-4-m is toxigenic)pyrimidine-2,4-diamine,
5-(2-isopropyl-4-methoxy-5-thiophene-2-elfenix)pyrimidine-2,4-diamine,
5-(2,4-diaminopirimidina-5-yloxy)-4-isopropyl-2-methoxy-N-methylbenzenesulfonamide,
5-(2-isopropyl-5-methanesulfonyl-4-methoxyphenoxy)-N2-methylpyrimidin-2,4-diamine,
5-(2-isopropyl-4-methoxy-5-pyrrol-1-elfenix)pyrimidine-2,4-diamine,
5-[2-isopropyl-4-methoxy-5-(4-methylthiophene-2-yl)phenoxy]pyrimidine-2,4-diamine,
5-(2-isopropyl-4-methoxy-5-thiazole-5-elfenix)pyrimidine-2,4-diamine,
5-(2-isopropyl-4-methoxy-5-oxazol-5-elfenix)pyrimidine-2,4-diamine,
5-[2-isopropyl-4-methoxy-5-(4-methylthiophene-3-yl)phenoxy]pyrimidine-2,4-diamine,
5-(2-isopropyl-4-methoxy-5-[1,2,4]triazole-1-elfenix)pyrimidine-2,4-diamine,
5-[2-isopropyl-4-methoxy-5-(2-methylthiazole-5-yl)phenoxy]pyrimidine-2,4-diamine,
5-(2-isopropyl-4-methoxy-6-methylphenoxy)pyrimidine-2,4-diamine,
5-(5-econsultancy-2-isopropyl-4-methoxyphenoxy)pyrimidine-2,4-diamine,
1-[5-(2,4-diaminopirimidina-5-yloxy)-4-isopropyl-2-methoxyphenyl]-1H-imidazole-2-thiol,
5-[2-isopropyl-4-methoxy-5-(1-methyl-1H-pyrazole-4-yl)phenoxy]pyrimidine-2,4-diamine,
5-(5-fluoro-2-isopropyl-4-methoxyphenoxy)pyrimidine-2,4-diamine,
2-[5-(2,4-diaminopirimidina-5-yloxy)-4-isopropyl-2-methoxyphenyl]propan-2-ol,
5-(2,4-diaminopirimidina-5-yloxy)-N-ethyl-4-isopropyl-2-methoxybenzenesulfonamide,
5-[5-(2,5-dimethylpyrrole-1-yl)-2-isopropyl-4-methoxyphenoxy]pyrimidine-2,4-diamine.

4. The compound according to claim 3, before the bringing of a
5-(2,4-diaminopirimidina-5-yloxy)-4-isopropyl-2-methoxybenzenesulfonamide;
1-[5-(2,4-diaminopirimidina-5-yloxy)-4-isopropyl-2-methoxyphenyl]Etalon; or
5-(5-iodo-2-isopropyl-4-methoxyphenoxy)pyrimidine-2,4-diamine.

5. Pharmaceutical composition having antagonistic activity against receptors RH3including pharmaceutically acceptable excipient and an effective amount of a compound according to claim 1.

6. The use of compounds according to claim 1 for obtaining a medicinal product intended for the treatment of diseases mediated by the receptor antagonist RH3.

7. The use according to claim 6, where the disease is a disease of the genitourinary system or a disease associated with pain.

8. The use according to claim 7, where the disease of the genitourinary system is a reduced capacity of the bladder; frequent urination; urgency urinary incontinence; stress incontinence; increased reactivity of the bladder, benign hyperplasia of the prostate; prostatitis; detrusor hyperreflexia; frequent urination; nycturia (nocturnal polyuria); urgent need to pass urine; hyperreactivity bladder; increased sensitivity in the pelvic region; urethritis; prostatitis; pain in the pelvic region, p is ottolini (pain in the prostate gland); cystitis; or idiopathic hypersensitivity of the bladder; and the disease, which is associated with pain is a pain, and inflammation; pain during surgical exposure; visceral pain; tooth pain; premenstrual pain, Central pain, pain in the burns; migraine or severe attacks of headache with periodic relapses; pain when nerve damage; pain neuritis; pain in neuralgia; pain in case of poisoning; pain in trauma-related circulatory disorders; pain in interstitial cystitis; pain in cancer; pain, viral, parasitic or bacterial infection; pain in post-traumatic injury; or pain associated with irritable bowel syndrome.



 

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FIELD: medicine.

SUBSTANCE: in formula (I) , the ring A represents 6-members aryl or 5-6-members heteroaryl containing 1-2 heteroatoms selected from nitrogen and sulphur; Q means C3-8 cycloalkyl, 5-6-members heterocycle containing 1 heteroatom selected from oxygen, nitrogen or sulphur, C1-6 alkyl or C2-6 alkenyl; the ring T represents 5, 6, 9 or 10-members heteroaryl or 9-members heterocycle optionally additionally substituted by 1-3 heteroatoms independently selected from nitrogen or sulphur. The values of other substitutes are specified in the patent claim. Also, the invention refers to methods for preparing oxime derivatives of general formula (I), to pharmaceutical compositions containing the compound of the invention as an active ingredient and to applications of the compounds of the invention in preparing a drug.

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FIELD: medicine.

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20 cl, 20 tbl, 6 dwg, 7 ex

FIELD: medicine.

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13 cl, 36 ex, 1 tbl

FIELD: chemistry.

SUBSTANCE: present invention relates to hot or sweet flavourants in form of a synthetic amide compound or edible salt thereof in amount ranging from approximately 0.001 parts per million to approximately 100 parts per million. The amide compound has formula

where A is a phenyl or a 5- or 6-member heteroaryl ring selected from a group comprising pyridine, pyrazine, pyrazole, thiazole, furan, thiophene, benzofuran and benzothiophene; m equals 1, 2 or 3, each R1 is independently selected from hydroxyl, fluorine, chlorine, SEt, SCH3, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy and isopropoxy, or alternatively two R1 are bonded to form a saturated C1-C3 alkylenedioxy ring on the phenyl; and R2 is a C3-C10 branched alkyl. The amide compound also has formula

in which substitutes A, B, R50, R60, R70, R80, n and m assume values given in the formula of invention. The amide compound is also a specific chemical compound.

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39 cl, 7 tbl, 180 ex

Aromatic compound // 2416608

FIELD: chemistry.

SUBSTANCE: invention describes a novel compound of general formula (1), where radicals R1, R2, X1, Y and A are as described in claim 1 of the invention. The invention also describes a method of obtaining compounds of formula (1), as well as a pharmaceutical composition based on said compounds, for treating fibrosis.

EFFECT: novel compounds with excellent collagen formation suppression, cause fewer side-effects and which are safer are obtained.

62 cl, 2717 ex, 432 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of formula (I) or pharmaceutically acceptable salts thereof, where Q is CH or N; R2 is C1-C4 alkyl or C3-C4-cycloalkyl; Y is R5-O; where R5 is propynyl; X is selected from a group consisting of aryl, heteroaryl, C1-C5-alkyloxy, heterocycloalkyl, arylamino, heteroarylamino, heteroaryl-C1-C4-alkylamino, aryloxy, aryl-C1-C2-alkyloxy or C3-C6-cycloalkyl-C1-C4-alkyloxy, each of which is optionally substituted with 1-3 times; the optional substitute(s) for X is(are) independently selected from a group comprising halogen, cyano, trifluoromethyl, nitro, hydroxy, C1-C4-alkyl, C1-C4-alkoxy, C1-C4-alkyloxy-C1-C4-alkoxy, -SMe, SO2-C1-C2-alkyl, -NMe2, - C(O)O-C1-C5-alkyl, -SCF3, -SO2-NH2, -SO2-C2-alkyl-OH, -CONH2, -COMe, - CONH-C1-C4-alkyl, -CONMe2, -NHCOMe, -CH2COOEt, -OCH2COOEt, -CH2- cyclopropyl, and each R3 and R4 is H; where aryl denotes phenyl or naphthyl; heteroaryl denotes monocyclic or bicyclic hydrocarbon containing 5-10 ring atoms, one or more of which are heteroatoms selected from O, N or S; heterocyclyl denotes piperidinyl or benzodioxolyl; or a compound or pharmaceutically acceptable salt thereof, selected from a group comprising (4-dimethylaminophenyl)-[4-(4-cyclopropylphenyl)-6-propargyloxyquinazolin-2-yl]methanone, (3-sulphamoylphenyl)amide 4-(4-isopropylphenyl)-6-prop-2-ynyloxy-3,4-dihydroquinazoline-2-carboxylic acid, [3-(2-hydroxyethanesulphonyl)phenyl]amide 4-(4-isopropylphenyl)-6-prop-2-ynyloxy-3,4-dihydroquinazoline-2-carboxylic acid, (3-methylsulphanylphenyl)amide 4-(4-isopropylphenyl)-6-prop-2-ynyloxy-3,4-dihydroquinazoline-2-carboxylic acid, (3-methanesulphonylphenyl)amide 4-(4-isopropylphenyl)-6-prop-2-ynyloxy-3,4-dihydroquinazoline-2-carboxylic acid, and (5-ethanesulphonyl-2-hydroxyphenyl)amide 4-(4-isopropylphenyl)-6-prop-2-ynyloxy-3,4- dihydroquinazoline -2-carboxylic acid. The invention also relates to a pharmaceutical composition based on the compound of formula (I) and use of the compound of formula (I).

EFFECT: novel benzoquinazoline derivatives, which are useful in treating bone disorders, are obtained.

6 cl, 128 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new cyclopenta[b]benzofuranyl derivatives of formula wherein substitutes R1, R2, R3, R4, R5, R6 and R7 and n are specified in the patent clam. These compounds exhibit properties of NF-kB-activity and/or AP-1 inhibitor/modulator. Also, the inventive subject matter are methods for preparing intermediate compounds thereof, a pharmaceutical composition containing them, administration thereof for prevention and/or treatment of inflammatory and autoimmune diseases, neurodegenerative diseases and hyperproliferative diseases caused by NF-kB- and/or AP-1-activity, and a method for prevention and/or treatment of said diseases.

EFFECT: preparation of new cyclopenta[b]benzofuranyl derivatives.

21 cl, 3 tbl, 151 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: compound of formula pharmaceutically acceptable salt or solvate of a compound or salt (I), ring Q represents optionally substituted monocyclic or condensed (C6-C12)aryl or optionally substituted monocyclic or condensed heteroaryl where said substitutes are chosen from: halogen; (C1-C6)alkyl optionally substituted by 1-3 halogen atoms; (C1-C6)alkylsulphonyl; phenyl optionally substituted by 1 or 2 substitutes chosen from halogen, (C1-C6)alkyl which can be substituted by 1-3 halogen atoms, groups (C1-C6)alkylamino, di(C1-C6)alkylamino, (C1-C6)alkoxy, (C1-C6)alkoxy(C1-C6)alkyl and (C1-C6)alkylthio; monocyclic or condensed heteroaryl optionally substituted by halogen; or oxo; Y1 represents a bond or -NR6-CO-, where R6 represents hydrogen, ring A represents optionally substituted a nonaromatic heterocyclyldiyl where said substitutes are chosen from (C1-C6)alkyl optionally substituted by groups hydroxy, (C1-C6)alkylamino, di(C1-C6)alkylamino, morpholino, (C1-C6)alkylaminocarbonyl, di(C1-C6)alkylaminocarbonyl; cyano; (C3-C6)cycloalkyl; (C1-C6)alkoxy; (C1-C6)alkoxy(C1-C6)alkyl; phenyl; benzyl; benzyloxymethyl; thienyl; 4-8-members monocyclic nonaromatic heterocycle having 1 or 2 heteroatoms chosen from N or O, and optionally substituted by 1 or 2 substitutes chosen from (C1-C6)alkyl, (C1-C6)alkoxy, (C1-C6)alkoxy(C1-C6)alkyl and oxo; (C1-C6)alkylamino; di(C1-C6)alkylamino; a group of formula: -Y2Z'- represents a group of formula: [Formula 2] each R7 independently represents hydrogen, (C1-C6)alkyl or (C3-C6)cycloalkyl, each of R8 and R9 independently represents hydrogen or (C1-C6)alkyl, n is equal to an integer 0 to 3, Z1 represents a bond, -O-, -S- or-NR9 - where R9 represents hydrogen, (C1-C6)alkyl, acyl or (C1-C6)alkylsulphonyl, ring B represents optionally substituted aromatic carbocyclediyl or optionally substituted aromatic heterocyclediyl where said substitutes are chosen from (C1-C6)alkyl, halogen, (C1-C6)alkoxy and oxo; Y3 represents a bond optionally substituted (C1-C6)alkylene or (C3-C6)cycloalylene, optionally interrupted -O- or optionally substituted (C2-C6)alkenylene where said substitutes are chosen from (C1-C6)alkyl, (C3-C6)cycloalkyl, halogen and (C1-C6)alkoxycarbonyl; Z2 represents COOR3; R3 represents hydrogen or (C1-C6)alkyl.

EFFECT: preparation of new compounds.

30 cl, 9 tbl, 944 ex

FIELD: medicine.

SUBSTANCE: compounds of the invention exhibit properties of β2- adrenoreceptor agonists. In formula (I) , R1 represents hydrogen; each R2, R3, R4, R5, R4' and R5' independently represents hydrogen or C1-C6alkyd; e is equal to 0 or 1; A represents C(O); D represents oxygen or sulphur; m is equal to an integer 0 to 3; n is equal to an integer 0 to 3; R6 represents the group -(X)p-Y-(Z)q-R10; each X and Z independently represents C1-C6akylene group; each p and q is independently equal to 0 or 1; Y represents a bond, oxygen, CH2 or NR9; R7a and R7b independently represent hydrogen or C1-C6alkyl; R9 represents C1-C6alkyl; R10 represents hydrogen or saturated or unsaturated 6-members ring system optionally containing at least one ring heteroatom, chosen of nitrogen. And this ring system is optionally substituted by C1-C6alkoxycarbonyl; R7 represents 6-12-members aromatic ring system which is optionally substituted by halogen, trifluoromethyl, hydroxyl, C1-C6alkyl, C1-C6alkoxy or NH2; provided R6 does not represent hydrogen or unsubsituted C1-C6alkyl group. Also, the invention refers to methods for producing compounds of formula (I), to a pharmaceutical composition exhibiting properties of β2- adrenoreceptor agonists containing the compound of formula (I) as an active ingredient, to application of the compound of formula (I) in preparing a drug, to a combination containing the compound of formula (I) and one or more agents.

EFFECT: improved properties of the composition.

27 cl, 2 tbl, 32 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel derivatives of isothiazole-3(2H)-OH-1,1-dioxides of formula (I) or pharmaceutically acceptable salts thereof, which can increase expression of LXR α and/or β, a pharmaceutical composition based on said derivatives, use thereof in preparing a medicinal agent, as well as novel intermediate compounds of formula (V) or salts thereof. In formulae (I), (V) R2 denotes phenyl, and R1 and R3 are as described in the claim.

EFFECT: improved properties of the derivatives.

7 cl, 9 dwg, 172 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel oxadiazole compounds of formula (1) and pharmaceutically acceptable salts thereof, where R1 and R2 assume values given in the description, Y is a single bond. The invention also relates to use of said compounds as DGAT1 inhibitors, for example for treating obesity and diabetes, and a method of inhibiting.

EFFECT: high treatment efficiency.

13 cl, 65 tbl, 712 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula , where R1 is a 3-7-member carbocyclic ring and n is a number ranging from 1 to 8, and the rest of the radicals are described in the claim.

EFFECT: possibility of using such compounds and compositions in therapy as metabotropic glutamate receptor modulators.

33 cl, 367 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds of general formula

where there are R3/R3', R4/R4' and R5/R5' where at least one of either R4/R4' or R5/R5' always represents a fluorine atom, and the other radical values are disclosed in the description.

EFFECT: making the compounds which are γ-secretase inhibitors, and can be effective in treating Alzheimer's disease or advanced cancers, including but not limited to carcinoma of uterine cervix and breast carcinoma and malignant tumours of hematopoietic system.

15 cl, 3 tbl, 18 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to novel 3,4-substituted pyrrolidine derivatives of general formula or pharmaceutically acceptable salts thereof, where R1 is an acyl selected from values given paragraph 1 of the formula of invention; R2 is unsubstituted C1-C4-alkyl or C3-C7-cycloalkyl; R3 is a fragment selected from a group of fragments of formulae: (a), (b),

(c) and (f), where any of the fragments of formulae given above (a), (b) and (f), the star (*) indicates a bond of the corresponding fragment R3 with the molecule residue in formula I; Ra denotes N-C1-C4-alkylaminocarbonyl, N-phenylaminocarbonyl, N-(phenyl-C1-C4-alkyl)aminocarbonyl, N-(C1-C4-alkyl)-N-(phenyl-C1-C4-alkyl)aminocarbonyl, N-(C3-C7-cycloalkyl- C1-C4-alkyl)-N-(phenyl-C1-C4-alkyl)aminocarbonyl, N-(C1-C4-alkyl)-N-(C3-C7-cycloalkyl-C1-C4-alkyl)aminocarbonyl, N,N-di-(C1-C4-alkyl)aminocarbonyl, N-(C3-C7-cycloalkyl)-N-(phenyl-C1-C4-alkyl)aminocarbonyl, N-(C3-C7-cycloalkyl)-N-(tetrahydropyranyl-C1-C4-alkyl)aminocarbonyl, N-(C3-C7-cycloalkyl)-N-(tetrahydropyranyl)aminocarbonyl or hydrogen; Rb and Rc are independently selected from a group comprising unsubstituted C1-C4-alkyl, unsubstituted monocyclic aryl, unsubstituted monocyclic heterocyclyl, unsubstituted or substituted monocyclic C3-C7-cycloalkyl, unsubstituted aryl- C1-C4-alkyl, usubstituted monocyclic C3-C7-cycloalkyl- C1-C4-alkyl, hydrogen or acyl, where the acyl is selected from values given in paragraph 1 of the formula of invention; or Rb and Rc together may form a 6-member nitrogen-containing ring which may be unsubstituted or disubstituted with =O; Rd in the fragment of formula (c) denotes a phenyl or phenyl-C1-C4-alkyl; Re denotes hydrogen or C1-C4-alkyl; and m equals 2; each of R4 and R5 denotes hydrogen; and T denotes methylene. The invention also relates to the pharmaceutical composition based on the compound of formula I and a method of treating hypertension using the compound of formula I.

EFFECT: novel pyrrolidine derivatives having renin inhibiting activity are obtained.

7 cl, 19 tbl, 37 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to oxazole compound represented by formula (1) and its pharmaceutically acceptable salts. In formula (1) R1 represents phenyl group, which can contain one or two substituents, selected from the following groups (1-1)-(1-11): (1-1) hydroxy groups, (1-2) unsubstituted or halogen-substituted lower alkoxy groups, (1-3) lower alkenyloxy-groups, (1-4) lower alkinyloxy groups, (1-5) cycloC3-8alkyl (lower) alkoxy groups, (1-6) cycloC3-8alkyloxy groups, (1-7) cycloC3-8alkenyloxy groups, (1-8) dihydroindenyloxy groups, (1-9) hydroxyl-(lower)ankoxy groups, (1-10) oxiranyl(lower)alkoxy groups, and (1-11) phenyl(lower)-alkoxy groups; R2 represents phenyl group or heterocyclyl group, selected from pyridine, pyrasine, isoquinoline, pyrrolidine, piperazine, morpholine, each of which can contain one or two substituents, selected from the following groups (2-1)-(2-10):(2-1) hydroxy groups, (2-2) unsubstituted or halogen-substituted lower alkoxy groups, (2-3) unsubstituted or halogen-substituted lower alkyl groups, (2-4) lower alkenyloxy groups, (2-5) halogen atoms, (2-6) lower alkanoyl groups, (2-7) lower alkylthio groups, (2-8) lower alkylsulphonyl groups, (2-9) oxo groups and (2-10) groups lower alkoxy-lower alkoxy; and W represents bivalent group represented by formula (i) or (ii): formula (i) -Y -A -, formula (ii) -Y2-C(=O)-, where A1 represents lower alkenylene group or lower alkylene group, which can contain one substitutent, selected from group, consisting from hydroxy group and lower alkoxicarbonyl group, Y1 represents simple bond, -C(=O)-, -C(=O)-N(R3)-, -N(R4)-C(=O)-, -S(O)m-NH- or -S(O)n-, where R3 and R4, each independently, represent a hydrogen atom or lower alkyl group, and m and n, each independently, represent integer, which has value 2, and Y represents pyperazine-diyl group, or bivalent group, represented by formula (iii) or (iv): formula (iii) -C (=O)-A2-N(R5)-, formula (iv) A3-N(R6)-, where A2 and A3, each independently, represent lower alkylene group, and R5 and R6, each independently, represent a hydrogen atom. Invention also relates to pharmaceutical composition, containing the invention compound as an active ingredient, to pharmaceutical composition for treatment or prevention of atopic dermatitis, which includes the invention compound, to application of the compound as medication, to application of the compound as phosphodiesterase 4 inhibitor and/or as inhibitor of production of tumour necrosis factor α and to method of treatment or prevention of diseases, mediated by phosphodiesterase 4 or mediated by tumour necrosis factor α, including introduction of efficient dose of the compound.

EFFECT: creation of pharmaceutical composition for treatment or prevention of diseases mediated by phosphodiesterase 4 or mediated by tumour necrosis factor, as well as for treatment or prevention of atopic dermatitis.

12 cl, 42 tbl, 486 ex

FIELD: chemistry.

SUBSTANCE: invention relates to (3-trifluromethylphenyl)amide 6-(6-hydroxymethylpyrimidin-4-yloxy)naphthalene-1-carboxylic acid or tautomer or salt thereof. The invention also relates to a pharmaceutical composition which has protein kinase inhibiting activity, based on the said compound and use of the said compound to prepare pharmaceutical compositions for use in treating protein kinase dependent diseases, preferably proliferative diseases, particularly tumorous diseases.

EFFECT: improved properties of compounds.

6 cl, 115 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula (I) or pharmaceutically acceptable salts, solvates or tautomers thereof, where substitute M is selected from groups D1 and D2, having structural formulae given below, and R1, E, A and X are as described in the formula of invention. Disclosed also are pharmaceutical compositions which contain these compounds, methods for synthesis of these compounds, intermediate compounds and synthesis methods thereof, as well as use of compounds of formula (I) in preventing or treating diseases mediated by CDK kinases, GSK-3 kinases or Aurora kinases.

EFFECT: high effectiveness of the compounds.

40 cl, 8 dwg, 18 tbl, 84 ex

Aromatic compound // 2416608

FIELD: chemistry.

SUBSTANCE: invention describes a novel compound of general formula (1), where radicals R1, R2, X1, Y and A are as described in claim 1 of the invention. The invention also describes a method of obtaining compounds of formula (1), as well as a pharmaceutical composition based on said compounds, for treating fibrosis.

EFFECT: novel compounds with excellent collagen formation suppression, cause fewer side-effects and which are safer are obtained.

62 cl, 2717 ex, 432 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to novel benzo[d]isoxazol-3-ylamine compounds of formula I in free form or in form of salts with physiologically compatible acids, having antagonistic effect on KCNQ2/3 ion channel. In formula I , R1, R2, R3 and R4 independently denote H, F, CI, Br, I, -NR7R8, -OR9 or C1-C10alkyl, R5 denotes -C(=S)NR21R22 or (CHR6)n-R25, where n equals 1, 2 or 3, R6 denotes H or C1-C6 alkyl, R25 denotes aryl or heteroaryl, R7 and R8 independently denote H or C1-C10 alkyl, R9 denotes H, C1-C10alkyl or -(C1-C5alkylene)aryl, R21 denotes H, R22 denotes C1-C10alkyl, C2-C10alkenyl, C3-C8cycloalkyl, -(C1-C5alkylene)-C3-C8cycloalkyl, -(C1-C3alkylene)heterocycloalkyl, aryl, heteroaryl or -(C1-C5alkylene)aryl, wherein each of the heterocycloalkyl residues has 5-6 members, contains 1 or 2 heteroatoms in the ring, independently selected from oxygen and nitrogen, each of the aryl residues is phenyl, anthracenyl or naphthyl, each of the heteroaryl residues has 5 or 6 members and contains 1 or 2 heteroatoms in the ring, independently selected from oxygen, sulphur and nitrogen.

EFFECT: said compounds can be used to prepare a medicinal agent for curing pain, migraine, anxiety, uroclepsia or epilepsy.

17 cl, 203 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula 1, compounds of formula 5 and pharmaceutically acceptable salts thereof. In formulae 1 5 Y denotes -C(O)-, X denotes -N(R11)-, R1 denotes a residue of formula 1a or 1b - for formula 1 or residue of formulae 5a or 5b - for formula 5 1a 1b 5a 5b, R2 and R7 independently denote H, hydroxyl or (C1-C6)alkyl; R3 and R6 each independently denotes H, hydroxyl or (C1-C6)alkyl; R4 and R5 each independently denotes H or (C1-C6)alkyl; the rest of the radicals are described in the formula of invention. The invention also relates to separate compounds given in the formula of invention, a pharmaceutical composition having Bcl bound protein inhibiting properties, which contains a therapeutically effective amount of the disclosed compound, a method of treating a bc1 mediated disorder, involving introduction of a therapeutically effective amount of the disclosed compound and a method of treating a bc1 mediated disorder involving administration to a patient in need of treatment of an effective amount of camptothecin and therapeutically effective amount of the disclosed compound.

EFFECT: high efficiency of the composition.

84 cl, 12 tbl, 1 dwg, 217 ex

FIELD: medicine.

SUBSTANCE: present invention presents new compounds which are modulators of cannabinoid receptors, particularly modulators of cannabinoid receptors 1 (CB1) or cannabinoid receptors 2 (CB2), and an application thereof for treating diseases, conditions and/or disorders regulated by a cannabinoid receptor (such as painful sensations, neurodegenerative disorders, ingestion disorders, weight loss or weight control and obesity), as well as based pharmaceutical compositions. New compounds are characterised by graphic formulas

in which radicals and groups have the values specified in the patent claim.

EFFECT: higher efficiency of applying the composition.

55 cl, 13 tbl, 3 dwg, 802 ex

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