Pyperidinyl naphthyluxic acids

FIELD: pharmacology.

SUBSTANCE: invention relates to compounds of formula (I): , as well as to pharmaceutically acceptable salts, pharmaceutical compositions and application thereof.

EFFECT: new compounds that are CRTH2 receptor antagonists have been obtained that can be useful for respiratory diseases treatment or prevention.

20 cl, 2 tbl, 37 ex

 



 

Same patents:

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to specific compounds or to their therapeutically acceptable salt presented in the patent claim and representing sulphonyl benzamide derivatives. The invention also refers to a pharmaceutical composition inhibiting the activity of anti-apoptotic proteins of the family Bcl-2, containing an excipient and an effective amount of a specific sulphonyl benzamide derivative.

EFFECT: sulphonyl benzamide derivatives inhibiting the activity of anti-apoptotic Bcl-2 proteins.

2 cl, 3 tbl, 558 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds of formula or its therapeutically acceptable salts, wherein A1 represents furyl, imidazolyl, isothiazolyl, isoxazolyl, pyrazolyl, pyrrolyl, thiazolyl, thiadiazolyl, thienyl, triazolyl, piperidinyl, morpholinyl, dihydro-1,3,4-thiadiazol-2-yl, benzothien-2-yl, banzothiazol-2-yl, tetrahydrothien-3-yl, [1,2,4]triazolo[1,5-a]pyrimidin-2-yl or imidazo[2,1-b][1,3]-thiazol-5-yl; wherein A1 is unsubstituted or substituted by one, or two, or three, or four, or five substitutes independently specified in R1, OR1, C(O)OR1, NHR1, N(R1)2, C(N)C(O)R1, C(O)NHR1, NHC(O)R1, NR1C(O)R1, (O), NO2, F, Cl, Br and CF3; R1 represents R2, R3, R4 or R5; R2 represents phenyl; R3 represents pyrazolyl or isoxazolyl; R4 represents piperidinyl; R5 represents C1-C10alkyl or C2-C10alkenyl each of which is not specified or specified by substitutes specified in R7, SR7, N(R7)2, NHC(O)R7, F and Cl; R7 represents R8, R9, R10 or R11; R8 represents phenyl; R9 represents oxadiazolyl; R10 represents morpholinyl, pyrrolidinyl or tetrahydropyranyl; R11 represents C1-C10alkyl; Z1 represents phenylene; Z2 represents piperidine unsubstituted or substituted by OCH3, or piperazine; both Z1A and Z2A are absent; L1 represents C1-C10alkyl or C2-C10alkenyl each of which is unsubstituted or substituted by R37B; R37B represents phenyl; Z3 represents R38 or R40; R38 represents phenyl; R40 represents cyclohexyl or cyclohexenyl; wherein phenylene presented by Z1 is unsubstituted or substituted by the group OR41; R41 represents R42 or R43; R42 represents phenyl, which is uncondensed or condensed with pyrrolyl, imidazolyl or pyrazole; R43 represents pyridinyl, which is uncondensed or condensed with pyrrolyl; wherein each cyclic fragment presented by R2, R3, R4, R8, R9, R10, R38, R40, R42 and R43 is independently unsubstituted or substituted by one or more substitutes independently specified in R57, OR57, C(O)OR57, F, Cl CF3 and Br; R57 represents R58 or R61; R58 represents phenyl; R61 represents C1-C10alkyl; and wherein phenyl presented by the group R58 is unsubstituted or substituted by one or more substitutes independently specified in F and Cl.

EFFECT: invention refers to a pharmaceutical composition containing the above compounds, and to a method of treating diseases involving the expression of anti-apoptotic Bcl-2 proteins.

7 cl, 2 tbl, 48 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula I, possessing a modulating action with respect to the CC chemokine receptor 3 (CCR3), a based on them pharmaceutical composition, versions of treatment methods and a method of controlling the CCR3 activity. In the general formula I R1 and R2 represent halogen or C1-6alkyl; R3 represents cyano or nitro; R4 represents or ; R5 represents oxo; C1-6alkyl, optionally substituted with halogen atoms; or C(O)OR1a; X represents O or S; Y represents -O-, -S-, -N(R1a)-, -C(R1a)(R1d)- or -C(R1a)(NR1bR1c)-; m represents an integer number from 0 to 2; n represents 1; p represents an integer number from 0 to 2; r represents 1 or 2; and each R1a, R1b, R1c and R1d represents (a) hydrogen; (b) C3-7cycloalkyl; or (c) C1-6alkyl, optionally substituted with hydroxyl, or each pair R1b and R1c together with a N atom, which they are bound to, form imidazoimidazolyl, substituted with oxo, butyl or chlorine, or heterocycle, containing 5 or 6 atoms in a cycle.

EFFECT: improvement of the composition properties.

41 cl, 2 tbl, 7 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to a novel derivative of N-acylanthranilic acid, represented by the following general formula 1, or to its pharmaceutically acceptable salt, in which R1, R2, R3, X1, X2, X3, X4 and A are determined in the invention formula.

EFFECT: invention relates to an inhibitor of collagen production, a medication for treating diseases, associated with the excessive production of collagen, containing N-acylanthranilic acid derivative Formula 1.

FIELD: chemistry.

SUBSTANCE: invention relates to 2,5 substituted arylsulphonamides of formula (Ia) or to their pharmaceutically acceptable salts, solvates, hydrates, stereoisomers or tautomers, where X represents S, SO or SO2; Y and Z represents (i) Y represents NR5; and Z represents =O, CO2R6 or C1-6alkyl; or (ii) Y represents CH2, CHF, CHCH3, O, S or SO2; and Z represents hydrogen or C1-6alkyl; R1 and R2 each independently represents halogen, C1-6alkyl or C1-6 halogenalkyl; R3 represents CN or NO2; R4 represents hydrogen or C1-6alkyl; R5 represents hydrogen or C1-6alkyl; and R6 represents hydrogen or C1-6alkyl. Invention also relates to compounds of formula (I) and (II), values of radicals of which are given in the invention formula, specific compounds, pharmaceutical composition based on compound of formula

,

and

,

method of modulating CCR3 activity.

EFFECT: obtained are novel compounds, possessing useful biological properties.

18 cl, 1 tbl, 3 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds of formula I and formula IV wherein the radical values are such as specified in cl. 1 and 4 of the patent claim, as well as to their therapeutically acceptable salts. Besides, the invention refers to a composition for treating cancer on the basis of the compounds of formula I, to using the compounds of formula I for preparing the therapeutic agent for treating cancer, as well as to using it for treating cancer.

EFFECT: there are prepared and described the new compounds which inhibit anti-apoptotic Bcl-2 and Bcl-x protein activity.

17 cl, 481 ex

FIELD: chemistry.

SUBSTANCE: described is a compound selected from a group consisting of formula II formula III and formula IV , or its salt or ester, where G1 is selected from a group which includes - (CR1R2)n-, n equals 0 or 1; R1 and R2 are independently selected from a group which includes hydrogen; X1, X2 and X3 are independently selected from a group consisting of hydrogen, optionally substituted lower alkyl, halogen, optionally substituted lower alkoxy, G2 is a heterocycloalkyl linker optionally substituted with X4 and X5, where the heterocycloalkyl linker is selected from a group consisting of piperazinyl, 3,6-dihydro-2N-pyridinyl, [1,4]diazepanyl, 3,9-diazabicyclo[3,3,1]nonyl; X4 and X5 are independently selected from a group consisting of hydrogen and optionally substituted lower alkyl; CO2R; R is selected from a group consisting of optionally substituted lower alkyl and hydrogen; G3 is a bond; G4 is selected from a group consisting of hydrogen, aryl, selected from phenyl which is optionally substituted with a lower alkyl, halogen, lower haloalkyl or lower haloalkoxy; heteroaryl selected from pyridinyl which is optionally substituted with a halogen or lower haloalkyl; and optionally substituted cycloheteroalkyl selected from 1,3-benzodioxolyl. Described also are specific compounds and a pharmaceutical composition.

EFFECT: disclosed compounds are used as modulators of receptors activated by a peroxisomal proliferator.

5 cl, 2 tbl, 117 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention describes novel compounds of the general formula (I) wherein p, R1, R2, R3 and A are determined in the invention description, their individual isomers and their pharmaceutically acceptable salts. Proposed compounds possess antagonistic effect with respect to muscarinic receptors that allows their using in treatment and prophylaxis of diseases yielding to treatment with muscarinic receptor antagonist. Also, invention describes a pharmaceutical composition containing these compounds.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.

23 cl, 22 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to compounds of the formula (I) as separate stereoisomers and their mixtures, or their physiologically acceptable salts possessing with inhibitory effect on VIIa factor. In the general formula of compounds of the formula (I) m = 0, 1, 2, 3 or 4; n = 0, 1, 2 or 3; A represents halogen atom; X represents oxygen atom; R1 is chosen from hydrogen atom, (C1-C6)-alkoxycarbonyl and (C6-C14)-aryloxycarbonyl wherein all aryl groups are free or substituted with (C1-C6)-alkoxy-group; R2is chosen from hydrogen atom, (C1-C6)-alkyl, (C6-C14)-aryl, (C6-C14)-aryl-(C1-C4)-alkyl, R20 -(C1-C6)-alkyl, R20-(C6-C14)-aryl and R20-(C6-C14)-(C1-C4)-alkyl wherein R20 is chosen from hydroxycarbonyl, aminocarbonyl; R3 is chosen from hydrogen atom, cyano-, hydroxy-group and (C1-C6)-alkyl; R4 is chosen from (C1-C6)-alkyl, (C-C14)-aryl, (C6-C14)-aryl-(C1-C4)-alkyl, Het and Het-(C1-C4)-alkyl wherin alkyl, atryl and Het groups are free or substituted with one or some similar or different substitutes R10; R5 is chosen from hydrogen atom, (C1-C6)-alkyl, (C6-C14)-aryl, (C6-C14)-aryl-(C1-C4)-alkyl wherein alkyl and aryl groups are free or substituted with one or some similar or different substituted R10; or R4 and R5 in common with carbon atom with that they are bound form saturated or unsaturated 5-6-membered ring that represents carbocyclic ring or heterocyclic ring comprising 1 or 2 similar ring heteroatoms chosen from nitrogen and oxygen atoms and possibly condensed with one or two saturated or unsaturated carbocyclic ring system comprising from 5 to 10 ring atoms wherein the final R4(R5)C-group is free or substituted with one or some similar or different substitutes R10; R6 is chosen from hydrogen atom and hydroxy-group. Also, invention relates to a method for synthesis of compound of the formula (I) and pharmaceutical composition based on thereof. Compounds of the formula (I) can be used in preparing medicinal agents useful for inhibition or decreasing blood coagulation or inflammatory response or for using in treatment of cardiovascular disorders, thrombo-embolic diseases or restenosis.

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

14 cl, 1 sch, 71 ex

FIELD: organic chemistry, chemical technology, medicine, biochemistry, pharmacy.

SUBSTANCE: invention relates to new derivatives of sulfonamides of the formula (I) or their pharmaceutically acceptable salts wherein R1 means -OH or -NHOH; R2 means hydrogen atom; R3 means alkyl, alkoxyalkyl, arylalkyl, pyridylalkyl or morpholinylalkyl; A means piperidyl or tetrahydrofuranyl; n = 0; E means a covalent bond; (C1-C4)-alkylene, -C(=O)-, -C(=O)O- or -SO2-; X means hydrogen atom, alkyl, aryl, arylalkyl, alkoxyalkyl, morpholinyl or tetrahydropyranyl; each among G and G' means -C(R5)=C(R5') wherein R5 and R5' mean hydrogen atom; M means the group -CH-; z means the group -(CR7R7')a-L-R8 wherein a = 0 and each among R7 and R7' means hydrogen atom; L means a covalent bond; R8 means halogen atom or alkoxy-group. Compounds of the formula (I) are inhibitors of metalloproteases and can be used for treatment of arthritis, cancer tumors and other diseases.

EFFECT: valuable medicinal properties of compounds.

15 cl, 7 tbl, 56 ex

FIELD: chemistry.

SUBSTANCE: invention relates to method of obtaining N,N-disubstituted N-{[alkyl(benzyl)sulfanyl]methyl} amines, which can be applied as novel modified means of plant ptotection against root rot and means, increasing productivity of crops. Essence of method lies in interaction of secondary amines of general formula RRNH with N,N-dimethyl-N-{[alkyl(benzyl)sulfanyl)methyl}- amines of general formula Me2N-CH2-SR' in presence of catalyst zinc chloride crystallohydrate ZnCl2-H2O at temperature 20 C and atmospheric pressure in chloroform as solvent for 5-7 h. Output of N,N-disubstituted N-{[alkyl(benzyl)sulfanyl]methyl} amines is 82-98%.

EFFECT: increased output of suitable product.

1 tbl, 1 ex

The invention relates to a new group of individual chemical compounds - cyclic amino compounds represented by the following formula:

< / BR>
where R1represents a phenyl group which may be optionally substituted by at least one Deputy, which represents a halogen atom; R2represents a C1-C8aliphatic acyl group or (C1-C4alkoxy) carbonyl group; and R3represents a saturated cyclic amino group which has from 2 to 8 carbon atoms in one or more cycles, with the highest nitrogen cycle has from 3 to 7 atoms in the cycle, and the specified saturated cyclic amino group substituted by a group having the formula-S-S-R4where R4and X have the meanings as defined below, and the said saturated cyclic amino group attached via its cyclic nitrogen atom adjacent to the carbon atom that is attached to the substituents R2and R1; R4represents a phenyl group which may be optionally substituted by at least one Deputy, selected IGP and nitro groups; WITH1-C6alkyl group which may be optionally substituted by at least one Deputy, selected from the group consisting of amino groups, carboxyl groups, (C1-C4alkoxy)carbonyl groups, substituents having the formula-NH-A1(where a1represents an-amino acid residue), and substituents having the formula-CO-AND2(where a2represents an-amino acid residue); or (C3-C8cycloalkyl group, and X represents a sulfur atom, sulfinol group or sulfonyloxy group, and the above-mentioned cyclic aminecontaining group may be optionally additionally substituted by a group having the formula = CR5R6where R5and R6are the same or different, and each independently represents a hydrogen atom, a carboxyl group, (C1-C4alkoxy)carbonyl group, karbamoilnuyu group, (C1-C4alkyl) karbamoilnuyu group or di-(C1-C4alkyl)karbamoilnuyu group; or their pharmacologically acceptable salts, pharmaceutical composition having inhibitory action in Rel is the prevention of disease, selected from the group consisting of embolism and thrombosis in a warm-blooded animal

The invention relates to new derivatives of 4-hydroxypiperidine General formula (I), where X denotes-O-, -NH-, -CH2-, -CH= , -CO2-, -SOP(lower alkyl) -, or-CONH-, R1- R4independently from each other, is hydrogen, hydroxy, nitro-group, a lower alkylsulfonyl, 1 - or 2-imidazolyl, 1-(1,2,4-triazolyl), R5and R6independently from each other, is hydrogen, lower alkyl, hydroxy - or oxoprop, R7- R10independently from each other, is hydrogen, lower alkyl, halogen, trifluoromethyl or lower alkoxygroup, n = 0 or 1, or their pharmaceutically acceptable acid additive salts

The invention relates to 1-phenylalanine - new ligands of 5-HT4receptors of formula I, where R1- halogen; R2- H, C1-C4alkoxy; R3- C1-C4alkoxy, phenyl C1-C4alkoxy, where phenyl optionally substituted by 1-3 substituents, independently selected from C1-C4of alkyl, C1-C4alkyloxy, 3,4-methylendioxy; R2and R3together represent methylenedioxy, Ethylenedioxy; R4denotes a group of formula (a) or (b), where n = 3, 4, 5; p = 0; q = 1 or 2; R5and R6each C1-C4alkyl or together are - (CH2)4- , - (CH2)6-, - (CH2)2O(CH2)2-,

-CHR8CH2CR9R10CHR11CH2- where R8and R11each H or together are - (CH2)t- where t =1; R9- H, HE, C1-C8alkyl, C1-C4alkyloxy; R10- H, C1-C8alkyl, phenyl, - (CH2)xR12where x = 0, 1, 2, 3; R12HE, C1-C4alkyloxy, - C(O)NR13R14, - NR13C(O)OR14, -SO2NR13R14, -NR13SO2R14, -NR13SO2NR14R15, -NR13C(O)NR14R15; R13, R14, R15- independently - H, C1-C4e is phenyl optionally substituted C1-C4alkyloxy, methylendioxy, Ethylenedioxy; or R7- (CH2)z- R12where z = 2, 3

The invention relates to new cyclic amine derivatives of General formula I, where R1represents a phenyl group substituted by halogen atom,2represents C1- C8aliphatic acyl group or (C1- C4alkoxy)carbonyl group, R3represents a 3 - to 7-membered saturated cyclic amino group which may form a condensed ring, where the specified cyclic amino group substituted by the Deputy selected from the group comprising: mercaptopropyl, which can be unprotected or protected by a group selected from a number of protective groups, C1- C4alkyl group, substituted mercaptopropyl, which can be unprotected or protected by a group selected from a number of protective groups, and the number of protective groups for the specified mercaptopropyl includes C1- C20alcoholnye group, C3- C20alkenone group and benzoline group, and the said cyclic amino group, furthermore preferably a substituted group of the formula =CR4R5where R4represents a hydrogen atom, and R5represents a hydrogen atom, a C1- C4alkyl group, carboxypropyl, (C1- C4-alkoxy)carbonyl GRU

The invention relates to new derivatives of acetic acid, the method of production thereof, pharmaceutical preparations containing such compounds and to the use of these compounds in the manufacture of pharmaceutical preparations

FIELD: chemistry.

SUBSTANCE: invention relates to method of obtaining hydrochloride of tertbutyl ester of (4-fluoro-3-pyperidin-4-yl-benzyl)-carbamic acid (I). Method includes reduction of tertbutyl ester of (4-fluoro-3-pyridin-4-yl-benzyl) carbamic acid under conditions of reducing hedrogenisation and then HCl processing with output of hydrochloride of tertbutyl esther of (4-fluoro-3-pyperidin-4-yl-benzyl)-carbamic acid. Also claimed are methods of obtaining intermediate products, namely 5-((tert-butoxycarbonyl)aminomethyl)-2-fluorobenzeneboronic acid and tertbutyl ester of (4-fluoro-3-pyridin-4-yl)benzyl-carbamic acid.

EFFECT: invention makes it possible to considerably simplify obtaining hydrochloride of tertbutyl esther of (4-fluoro-3-pyperidin-4-yl-benzyl)-carbamic acid.

30 cl, 1 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel substituted tetracyclic derivatives of tetrahydropyran, pyrrolidine and tetrahydrothiophene of general formula (I), their pharmaceutically acceptable addition salts, their stereochemically isomeric forms, their N-oxide forms, in which all substitutes are defined in claim 1 of the formula of invention. These compounds have binding affinity to serotonin receptors, particularly 5-HT2A and 5-HT2C receptors, and to dopamine receptors particularly D2 dopamine receptors, and have norepiniphrine reuptake inhibition properties. The invention also relates to a pharmaceutical composition containing said compounds, method of preparing said composition and use of said compounds as medicinal agents, particularly for preventing and/or treating several psychiatric and neurological disorders.

EFFECT: new compounds have useful biological properties.

12 cl, 3 tbl, 49 ex

FIELD: chemistry.

SUBSTANCE: present invention refers to the new compounds of formula 1: whereat : X is N or CH; R1 is selected from the group consisting of OSO2CH3, SOR4, SO2R4, SO2NH2, SO2NHCH3, SO2N(CH3)2, COR4, CN, OCF3, CF3, F, Cl, Br, I, CH(OH)CF3, CH2SO2CF3, CH2SO2CH3, CH2CF3, CH2COCH3, CH2COCF3; R2 is selected from the group consisting of CN, CF3, OH, OR4, F, CI, Br, I, CH3; R3 is selected from the group consisting of C1-C4 alkyls, allyl, CH2CH2OCH3, CH2CH2CH2F, CH2CH2CHF2, CH2CH2F, CH2CHF2, CH2CF3, 3,3,3-trifluoropropyl, 4,4,4-trifluorobuthyl; CH2CH2OH, CH2CH2CH2OH, CH2CH(OH)CH3, CH2CH2COCH3, , ;

R4 is selected from the group consisting of C1-C3 alkyls, CF3, CHF2, CH2F; provided that when R1 is CN, OCF3, CF3, F or Cl X is not CH, R2 is not F, CI, Br, CH3, and R3 is not C1-C3 alkyl or allyl; provided that when R1 is CF3 or CN, X is not CH, R2 is not F, CI, Br, CH3, and R3 is not C1-C2 alkyl; provided that when X is N: R1 is not Cl, when R2 is CH3, and R3 is CH2CH2OH; R1 is not Cl, when R2 is Cl, and R3 is CH3; R1 is not F, when R2 is CN, and R3 is CH3; R1 is not Cl, when R2 is Cl, and R3 is CH2CH2CH2OH; R1 is not Cl, when R2 is Cl, and R3 is CH2CH2OH; and provided that when R1 is SO2R4, SO2NH2, SO2NHCH3 or SO2N(CH3)2 R2 is not OH. The present invention refers also to the pharmaceutically acceptable salts of the said compounds, to the intermediate compounds, to their pharmaceutical composition as well as to the method of central nervous system abnormalities treatment.

EFFECT: obtaining of the new bioactive compounds active as modulators of dopamine neurotransmission.

43 cl, 79 ex, 7 tbl

FIELD: chemistry of heterocyclic compounds, organic chemistry, medicine, pharmacy.

SUBSTANCE: invention describes compound of the formula (Ib): or pharmaceutically acceptable hydrate of salt of indicated compound wherein R5 means oxygen atom (O); R6 means hydrogen atom (H); X means -CH2-, -CH(OH)(CH2)n- or -CH(NR11R12)- wherein n = 0; R11 and R12 mean independently hydrogen atom or (C1-C9)-alkyl or nitrogen atom (N), either R11 and R12 taken in common form 5-10-membered aromatic or nonaromatic carbocycle wherein 1-4 carbon atoms in ring are replaced independently with N, O or sulfur (S) atom and wherein at least of them represents nitrogen atom; R1, R2, R3, R4, R7, R8, R9 and R10 mean independently hydrogen atom or -A-B wherein A means -SO2-; B means -NZ1Z2, 5-10-membered aromatic or nonaromatic carbocycle wherein 1-4 carbon atoms in ring are replaced independently with N, O or S and wherein any of these atoms is unsubstituted or substituted with one or more groups comprising (C1-C10)-alkyl, (C1-C5)-alkylene-OC(O)-(C1-C5)-alkyl; Z1 and Z2 mean independently H or (C1-C10)-alkyl that is unsubstituted or substituted with one or more groups -N(Z3)(Z4) wherein Z and Z4 mean independently H or (C1-C5)-alkyl that is unsubstituted or substituted with one or more hydroxy-groups; either N, Z3 and Z4 taken in common form unsubstituted or substituted 5-10-membered aromatic or nonaromatic carbocycle wherein 1-4 carbon atoms in ring are replaced independently with N, O or S and wherein one of these atoms represents nitrogen atom.

EFFECT: valuable medicinal properties of compounds.

42 cl, 4 tbl, 2 ex

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