4-phenylpiperidine derivatives as renin inhibitors

FIELD: chemistry.

SUBSTANCE: invention relates to new compounds of formula , where R1 is -O-X, where X is -(CH2)m-(CR9R10)p-(CH2)n-Z-(CH2)q-W, where m, n and q are independently equal to zero or assume values from 1 to 5; p equals 0 or 1; R9 and R10 are independently hydrogen, hydroxy, halogen, lower alkyl, lower alkoxy or cycloalkyl; or R9 and R10 together represent alkylene, which together with the carbon atom to which the are bonded, form an aryl; Z is a bond or O, W is aryl; R2 is hydrogen; L is a bond; R3 is hydrogen; R4 is hydrogen; R5 and R6 are independently hydrogen; R7 is hydrogen, halogen, hydroxy, trifluromethyl, lower alkyl, lower alkoxy, alkanoyl, alkyloxyalkoxy, alkanoyloxy, amino, alkylamino, dialkylamino, acylamino, carbamoyl, carboxy, alkoxycarbonyl; or R5 and R6 together represent -(CH2)1-2-; Y is -(CH2)r-, -O-(CH2)r, -(CH2)r-O-, where r equals zero or assumes values from 1 to 3; Q together with atoms to which it is bonded form an aryl, pyridyl, pyrimidinyl, thienyl, furyl, pyrroliyl or indolyl ring; or to its pharmaceutically acceptable salts. The invention also relates to a method of inhibiting rennin activity in mammals, to a pharmaceutical composition, as well as to application.

EFFECT: obtaining new biologically active compounds with inhibitory activity towards renin.

23 cl, 52 ex

 

The text descriptions are given in facsimile form.

1. The compound of the formula

where R1represents-O-X, where
X represents -(CH2)m-(CR9 R10)p-(CH2)n-Z-(CH2)q-W, where
m, n and q independently represent zero or have a value from 1 to 5;
R denotes zero or 1;
R9and R10independently represent hydrogen, hydroxy, halogen, lower alkyl, lower alkoxy or cycloalkyl; or
R9and R10together they are alkylen, which together with the carbon atom to which they are attached, form an aryl;
Z represents a bond or O;
W represents aryl;
R2represents hydrogen;
L is a bond;
R3represents hydrogen;
R4represents hydrogen;
R5and R6independently represent hydrogen;
R7represents hydrogen, halogen, hydroxy, trifluoromethyl, lower alkyl, lower alkoxy, alkanoyl, alkyloxyalkyl, alkanoyloxy, amino, alkylamino, dialkylamino, acylamino, carbarnoyl, carboxy, alkoxycarbonyl; or
R7and R6together represent -(CH2)1-2-;
Y represents -(CH2)r-, -O-(CH2)r-, -(CH2)r-O-, where
r denotes zero or has a value of from 1 to 3;
Q together with the atoms to which it is attached, forms an aryl, peregrinae, pyrimidinyl, thienyl, pureline, pyrrolidine or indolenine ring;
or its pharmaceutically p is Jemima salt.

2. The compound according to claim 1,
where R1represents-O-X;
X represents -(CH2)m-(CR9R10)p-(CH2)n-Z-(CH2)q-W, where
m and n independently represent zero or have a value from 1 to 5;
R denotes zero or 1;
q denotes zero;
R9and R10independently represent hydrogen, hydroxy, halogen, lower alkyl, lower alkoxy or cycloalkyl; or
R9and R10together they are alkylen, which together with the carbon atom to which it is attached, forms aryl;
Z represents a bond or O;
W represents aryl;
R2represents hydrogen;
L is a bond;
R3represents hydrogen;
R4represents hydrogen;
R5and R6independently represent hydrogen;
R7represents hydrogen, halogen, hydroxy, trifluoromethyl, lower alkyl, lower alkoxy; or
R7and R6together represent -(CH2)1-2-;
Y represents -(CH2)r-where
r denotes zero;
Q together with the carbon atoms to which it is attached, forms an aryl, peregrinae, pyrimidinyl, thienyl, pureline, pyrrolidine or indolenine ring;
or its pharmaceutically acceptable salt.

3. The compound according to claim 2 of the formula

where R1, R2, L, R3, R4, R5, R6, R7and Q have the meanings defined in claim 2;
or its pharmaceutically acceptable salt.

4. The compound according to claim 2 of the formula

where R1, R2, L, R3, R4, R5, R6, R7and Q have the meanings defined in claim 2;
or its pharmaceutically acceptable salt.

5. The compound according to claim 4, where
R1represents-O-X, where
X represents -(CH2)m-(CR9R10)p-(CH2)n-Z-W, where
m and n independently represent zero or have a value of 1 or 2;
R denotes zero or 1;
R9and R10independently represent hydrogen, hydroxy, halogen, lower alkyl, lower alkoxy or cycloalkyl; or
R9and R10together they are alkylen, which together with the carbon atom to which it is attached, forms aryl;
Z represents a bond or O;
W represents aryl;
R2represents hydrogen;
L is a bond;
R3represents hydrogen;
R4represents hydrogen;
R5and R6independently represent hydrogen; or
R7and R6together represent -(CH2)1-2-;
Q together with the atoms to which it is attached, forms an aryl, peregrinae, pyrimi inline, thienyl, pureline, pyrrolidine or indolenine ring;
or its pharmaceutically acceptable salt.

6. The compound according to claim 5, where
R1represents-O-X, where
X represents -(CH2)m-(CR9R10)p-(CH2)n-Z-W, where
m and n independently represent zero or have a value of 1 or 2;
R denotes zero or 1;
R9and R10independently represent hydrogen or lower alkyl; or
Z represents a bond or O;
W represents aryl;
R2represents hydrogen;
L is a bond;
R3represents hydrogen;
R4represents hydrogen;
R5and R6independently represent hydrogen;
R7represents hydrogen, halogen, hydroxy, trifluoromethyl, lower alkyl, lower alkoxy; or
R7and R6together represent -(CH2)1-2-;
Q together with the atoms to which it is attached, forms an aryl, peregrinae, pyrimidinyl, thienyl, pureline, pyrrolidine or indolenine ring;
or its pharmaceutically acceptable salt.

7. The connection according to claim 6, where
Q together with the carbon atoms to which it is attached, forms peregrinae or pyrimidinyl ring;
or its pharmaceutically acceptable salt.

8. The connection according to claim 6, where
Q together with the atoms is of Pereda, to which it is attached, forms a thienyl, pureline, pyrrolidine or indolenine ring;
or its pharmaceutically acceptable salt.

9. The compound according to claim 5 of the formula

where R1represents-O-X, where
X represents -(CH2)m-(CR9R10)p-(CH2)n-Z-W, where
m, n and p independently represent zero or 1;
R9represents hydrogen;
R10represents hydrogen or lower alkyl;
Z represents a bond or O;
W represents aryl;
R2represents hydrogen;
R3represents hydrogen;
R5and R6independently represent hydrogen; or
R7and R6together represent -(CH2)1-2-;
or its pharmaceutically acceptable salt.

10. The connection according to claim 9, where
R1represents-O-S; and
X represents -(CH2)m-(CR9R10)p-(CH2)n-Z-W, where
m denotes 1;
n and p represent zero;
Z represents a bond;
W represents aryl;
R3represents hydrogen;
R5represents hydrogen;
R6represents hydrogen;
R7represents hydrogen;
or its pharmaceutically acceptable salt.

11. The connection of claim 10, where
W is the battle monocyclic aryl;
or its pharmaceutically acceptable salt.

12. The compound according to claim 5, where
p denotes 1;
R9and R10together they are alkylen, which together with the carbon atom to which it is attached, forms aryl;
or its pharmaceutically acceptable salt.

13. The connection section 12 of the formula

where R1represents-O-X, where
X represents -(CH2)m-CR9R10-(CH2)n-Z-W, where
m and n denotes 1;
Z represents a bond; or Z represents O;
W represents aryl;
R2represents hydrogen;
R3represents hydrogen;
R5and R6independently represent hydrogen;
R7represents hydrogen, halogen, hydroxy, trifluoromethyl, lower alkyl, lower alkoxy; or
R7and R6together represent -(CH2)1-2-;
or its pharmaceutically acceptable salt.

14. The connection indicated in paragraph 13, where
R1represents-O-S; and
X represents-CH2-CR9R10-CH2-Z-W, where
Z represents a bond;
W represents aryl;
R3represents hydrogen;
R5represents hydrogen;
R6represents hydrogen;
R7represents hydrogen;
or its pharmaceutically priemel who may salt.

15. A method of inhibiting renin activity in mammals, which includes an introduction to the needy in the mammal a therapeutically effective amount of a compound according to claim 1.

16. Pharmaceutical composition having inhibitory activity against renin, comprising a therapeutically effective amount of a compound according to claim 1 in combination with one or more pharmaceutically acceptable carriers.

17. Pharmaceutical composition having inhibitory activity against renin, comprising a therapeutically effective amount of a compound according to claim 1 in combination with a therapeutically effective amount of an anti-diabetic agent, a lipid-lowering agent, agent, anti-obesity or anti-hypertensive agent.

18. The pharmaceutical composition according to item 16 or 17, intended for the treatment of hypertension, atherosclerosis, unstable coronary syndrome, acute heart failure, hypertrophy of the heart, fibrosis of the heart, cardiomyopathy after heart attack, unstable coronary syndrome, diastolic dysfunction, chronic kidney disease, hepatic fibrosis, complications resulting from diabetes such as nephropathy, vasculopathies and neuropathy, diseases of the coronary vessels, restenosis due to angioplasty, increased intraocular pressure, glaucoma, abnormal vascular growth, hyperaldosteronism, cognitive impairment, Alzheimer's disease, dementia, state anxiety and cognitive disorders.

19. The pharmaceutical composition according to item 16 or 17, intended for use as a drug, which exhibits inhibitory activity against renin.

20. The use of the pharmaceutical composition according to item 16 or 17 for the manufacture of a medicinal product for the treatment of conditions associated with renin activity.

21. The use of compounds according to claim 1 for the manufacture of pharmaceutical compositions for the treatment of conditions associated with renin activity.

22. The application of claim 20 or 21, where the condition associated with the renin activity, selected from hypertension, atherosclerosis, unstable coronary syndrome, acute heart failure, hypertrophy of the heart, fibrosis of the heart, cardiomyopathy after heart attack, unstable coronary syndrome, diastolic dysfunction, chronic kidney disease, hepatic fibrosis, complications resulting from diabetes such as nephropathy, vasculopathies and neuropathy, diseases of the coronary vessels, restenosis due to angioplasty, increased intraocular pressure, glaucoma, abnormal vascular growth, hyperaldosteronism, cognitive impairment, disease, Alz is Amara, dementia, state anxiety and cognitive disorders.

23. The compound according to claim 1, intended for use as a drug, which exhibits inhibitory activity against renin.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention claims compounds of the formula (I) with radicals as described in the claim, and medicine with inhibition effect on glycine absorption, based on compound of the formula (I) .

EFFECT: medicine for diseases treatment where glycine absorption inhibition can be effective.

21 cl, 1 tbl, 173 ex

FIELD: organic chemistry, biochemistry.

SUBSTANCE: invention relates to compounds of the formula (I): wherein R1 means -lower alkyl, -CH2-aryl, -cycloalkyl, -(CH2)3, -OC(=O)CH3, -lower alcohol, -lower alkyl-R10, -CH2COOH or -CH2CH2OCH2CH3; R2 means -lower alkyl, -CH2-aryl, -lower alcohol, -CH2C(=O)-NH2 or lower alkyl-R10 wherein at least one radical among R1 or R2 means -CH3; R3 means -COOH, -lower alkyl-COOH, -lower alcohol, -CH2OCH2, -CH2NH2, -CHNHSO2R11, -C(=O)-R12, -(CH2)nNHC(=O)-R13, -(CH2)mC(=O)N-(R15)(R16), -C(=NH)-R17 or -(CH2)n-R18; R4 means hydrogen atom (-H), -lower alkoxy group, -O-C(R7R8)C(=O)-R19, -halogen atom, -SCH3, -C=CHC(=O)-R10, -CH2CH2C(=O)-R10, -O-lower alcohol, -OCH2CH(OH)CH2N=N±N-, -OCH2CH2OCH2CH2Cl, -NHC9=O)-CH2-lower alkyl, -O(CH2)n-cycloalkyl, -O-lower alkene or 5-membered unsaturated heterocyclic ring comprising one heteroatom representing sulfur (S) or oxygen (O) atom; R5 and R6 mean independently -H, -halogen atom or -lower alkoxy group; R7 and R8 mean independently -H or -CH3; R10 means 5-6-membered saturated heterocyclyl comprising 1 or 2 heteroatoms, such as N and O, and this group is bound with other moiety of molecule by a ring N atom; R11 means -CF3, -lower alkyl, -CH2Cl, -CH2CF3 or -R12; R12 means 5-6-membered saturated substituted or unsubstituted heterocyclic ring comprising 1 heteroatom, such as N, O and S wherein substituted ring represents heterocyclic ring substituted with -OH or -phenyl; R13 means -lower alkyl, -lower alkoxy group or -(CH2)nR14; R14 means 5-6-membered saturated or unsaturated heterocyclic ring comprising 1 and 2 heteroatoms, that are chosen from group comprising N and O; R15 means -H, -lower alkyl, -OH, -lower alkoxy group or -CH2COOCH2CH3; R17 means -lower alkoxy group, -NH2 or -N-lower alkyl; R18 means saturated or unsaturated 5-membered substituted or unsubstituted heterocyclic ring comprising from 1 to 4 heteroatoms, such as N, O and S wherein substituted ring represents heterocyclic ring that is substituted by one or two cyclic carbon atoms by =O, or it is substituted by cyclic N atom by -lower alcohol or -lower alkyl; R19 means -OH, -NHCH(CH3)2, -N(CH3)CH2-aryl, -N(CH3)-lower alkyl, 1-(aryl-(CH2)n-)-[1,4]-diazin-4-yl or 5-6-membered saturated heterocyclyl and optionally substituted with lower alkyl comprising 1 or 2 heteroatoms, such as N and O; m = 0, 1 or 2; n = 0 or 1, and their pharmaceutically acceptable salts and esters. Also, invention relates to a pharmaceutical composition possessing inhibitory activity with respect to GFAT and containing the effective amount of compound of the formula (I). Invention provides expanding assortment of agents possessing inhibitory activity with respect to GFAT. Proposed compounds can be used as inhibitors of GFAT, and pharmaceutical composition possessing inhibitory activity with respect to GFAT containing above said compound of the formula (I) also.

EFFECT: valuable biochemical properties of compounds and pharmaceutical composition.

25 cl, 134 ex

FIELD: organic chemistry, medicine, endocrinology.

SUBSTANCE: invention relates to novel compounds representing C-glycoside derivatives and their salts of the formula: wherein ring A represents (1) benzene ring; (2) five- or six-membered monocyclic heteroaryl ring comprising 1, 2 or 4 heteroatoms chosen from nitrogen (N) and sulfur (S) atoms but with exception of tetrazoles, or (3) unsaturated nine-membered bicyclic heterocycle comprising 1 heteroatom representing oxygen atom (O); ring B represents (1) unsaturated eight-nine-membered bicyclic heterocycle comprising 1 or 2 heteroatoms chosen from N, S and O; (2) saturated or unsaturated five- or six-membered monocyclic heterocycle comprising 1 or 2 heteroatoms chosen from N, S and O; (3) unsaturated nine-membered bicyclic carbocycle, or (4) benzene ring; X represents a bond or lower alkylene wherein values for ring A, ring B and X correlate so manner that (1) when ring A represents benzene ring then ring B is not benzene ring, or (2) when ring A represents benzene ring and ring B represents unsaturated eight-nine-membered bicyclic heterocycle comprising 1 or 2 heteroatoms chosen from N, S and O and comprising benzene ring or unsaturated nine-membered bicyclic carbocycle comprising benzene ring then X is bound to ring B in moiety distinct from benzene ring comprised in ring B; each among R1-R4 represents separately hydrogen atom, -C(=O)-lower alkyl or lower alkylene-aryl; each R5-R11 represents separately hydrogen atom, lower alkyl, halogen atom, -OH, =O, -NH2, halogen-substituted lower alkyl-sulfonyl, phenyl, saturated six-membered monocyclic heterocycle comprising 1 or 2 heteroatoms chosen from N and O, lower alkylene-OH, lower alkyl, -COOH, -CN, -C(=O)-O-lower alkyl, -O-lower alkyl, -O-cycloalkyl, -O-lower alkylene-OH, -O-lower alkylene-O-lower alkyl, -O-lower alkylene-COOH, -O-lower alkylene-C(=O)-O-lower alkyl, -O-lower alkylene-C(=O)-NH2, -O-lower alkylene-C(=O)-N-(lower alkyl)2, -O-lower alkylene-CH(OH)-CH2(OH), -O-lower alkylene-NH, -O-lower alkylene-NH-lower alkyl, -O-lower alkylene-N-(lower alkyl)2, -O-lower alkylene-NH-C(=O)-lower alkyl, -NH-lower alkyl, -N-(lower alkyl)2, -NH-lower alkylene-OH or NH-C(=O)-lower alkyl. Indicated derivatives can be used as inhibitor of co-transporter of Na+-glucose and especially as a therapeutic and/or prophylactic agent in diabetes mellitus, such as insulin-dependent diabetes mellitus (diabetes mellitus 1 type) and non-insulin-dependent diabetes mellitus (diabetes mellitus 2 type), and in diseases associated with diabetes mellitus, such as insulin-resistant diseases and obesity.

EFFECT: valuable medicinal properties of compounds.

11 cl, 41 tbl, 243 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new 1-(p-thienylbenzyl)-imidazoles of the formula (I): , wherein indicated residues represent the following values: R(1) means halogen atom, (C1-C4)-alkoxyl, (C1-C8)-alkoxyl wherein one carbon atom can be replaced with heteroatom oxygen atom (O); R(2) means CHO; R(3) means aryl; R(4) means hydrogen halogen atom; X means oxygen atom; Y means oxygen atom or -NH-; R(5) means (C1-C6)-alkyl; R(6) means (C1-C5)-alkyl in their any stereoisomeric forms and their mixtures taken in any ratios, and their physiologically acceptable salts. Compounds are strong agonists of angiotensin-(1-7) receptors and therefore they can be used as a drug for treatment and prophylaxis of arterial hypertension, heart hypertrophy, cardiac insufficiency, coronary diseases such as stenocardia, heart infarction, vascular restenosis after angioplasty, cardiomyopathy, endothelial dysfunction or endothelial injures, for example, as result of atherosclerosis processes, or in diabetes mellitus, and arterial and venous thrombosis also. Invention describes a pharmaceutical composition based on above said compounds and a method for their applying also.

EFFECT: valuable medicinal properties of compounds and composition.

10 cl, 19 ex

FIELD: organic chemistry, pharmacy.

SUBSTANCE: invention relates to new derivatives of benzimidazole represented by the following formula (I) or its salt:

wherein R1 represents (lower)-alkyl group; R2 represents aromatic (lower)-alkyl group that can be substituted with one or more groups taken among halogen atom, alkyl group, halogen-(lower)-alkyl group, nitro-group, aromatic group, aromatic (lower)-alkoxy-group, (lower)-cycloalkyloxy-(lower)-alkyl group, aromatic (lower)-alkyl group, aromatic (lower)-alkenyl group, aromatic (lower)-alkynyl group, aromatic oxy-(lower)-alkyl group, (lower)-cycloalkyl-(lower)-alkoxy-group, alkenyl group, (lower)-alkoxy-group, (lower)-alkylthio-group and (lower)-alkanesulfonylcarbamoyl group; R3 represents alkyl group, hydroxy-(lower)-alkyl group, alkenyl group, aromatic group, halogenated aromatic group, (lower)-alkyl aromatic group, (lower)-alkenyl aromatic group or aromatic (lower)-alkenyl group; -X- represents cross-linking group represented by one of the following formulas: (II) , (III) , (IV) , (V) . Also, invention relates to pharmaceutical compositions eliciting activity that reduces blood glucose level based on this compound. Invention provides preparing new compounds and pharmaceutical compositions based on thereof used for prophylaxis and treatment of damaged tolerance to glucose, diabetes mellitus, insulin-resistance syndrome, vascular failures syndrome, hyperlipidemia and cardiovascular disorders.

EFFECT: valuable medicinal properties of compounds and compositions.

16 cl, 1 tbl, 86 ex

The invention relates to new imidazole derivative of the formula (I):where R1represents phenyl or pyridinyl, substituted by substituents selected from the group comprising (1) phenyl, (2) furyl, thienyl, (3) halogen, (4) halogen(lower)alkyl, (5) lower alkylthio, (6) nitro, (7) lower alkenyl, optionally substituted phenyl, (8) lower quinil, optionally substituted phenyl, (9) lower alkoxy, optionally substituted cyclo(lower)alkyl or phenyl, (10) lower alkyl, optionally substituted, phenyloxy or (11) amino, optionally substituted protected carboxyla; R2represents lower alkyl; R3represents halogen or lower alkyl; R4represents (1) lower alkenyl, optionally substituted phenyl, (2) phenyl, optionally substituted lower alkyl or lower alkenyl, (3) lower alkyl or (4) thienyl, optionally substituted with halogen; a represents a lower alkylene and L represents a simple bond, a lower albaniles or lower alkylene, optionally substituted phenyl or pyridinyl, or-X-CH2- where X represents O or NR5where R5represents hydrogen or n is

The invention relates to the field of organic chemistry, specifically to new connections: dicyanodiamide, namely aralen-bis(2-aminothiophene-3-carbonitrile)am General formula

where R represents

Connection most effectively can be used as monomers for obtaining polyamides, polyazomethines and politician with phenylanaline groups with high values of viscosity and conductivity

The invention relates to new substituted phenyl derivatives, which are strong blockers chlorine ion channels and as such are useful in the treatment of sickle cell anemia, cerebral edema that accompanies ischemia or tumor, diarrhea, hypertension (diuretic), osteoporosis and to reduce the intraocular pressure for the treatment of disorders such as glaucoma

The invention relates to piperazine derivatives of General formula I, in which R1denotes pyridyl or phenyl, unsubstituted or once substituted Ph or 2 - or 3-Tiepolo, R2indicates Ph1or Het

FIELD: chemistry.

SUBSTANCE: invention relates to new benzimidazole derivatives with general formula (I), where A represents -CH2-, -C(O), -C(O)-C(Ra)(Rb)-, X represents a -CH- radical; Ra and Rb independently represent a hydrogen atom or (C1-C6)alkyl radical; R1 represents a hydrogen atom or (C1-C8)alkyl radical; R2 represents a (C1-C8)alkyl radical; R3 represents -(CH2)P-Z3, -C(O)-Z'3 or -C(O)-NH-Z"3; Z3 represents (C1-C6)alkyl, (C2-C6)alkenyl, (C1-C6)alkoxy, (C1-C6)alkylcarbonyl, (C1-C6)alkoxycarbonyl, (C1-C6)alkyl-N(RN)carbonyl, (C3-C7)cycloalkyl, aryl, arylthio or heteroaryl radical, Z3 is bonded to the -(CH2)P- through a carbon atom, heteroaryl radical, which is a 5-10- member heteroaryl, which contains 1-2 identical or different heteroatoms, chosen from sulphur, nitrogen or oxygen, and optionally substituted with one or more identical or different substitutes, chosen from halogen, nitro group or -(CH2)P'-V30-Y3; aryl radical, chosen from phenyl or naphthyl, optionally substituted with one or more identical or different substitutes, chosen from halogen, nitro group, cyano group, (C2-C6)alkenyl, pyrrolidinyl, phenyl, phenyloxy, phenylalkyloxy, 5-7- member heteroaryl, containing 1-3 nitrogen atoms and -(CH2)p'-V31-Y3; V30 represents -O-, -C(O)-, -C(O)-O- or a covalent bond; V31 represents -O-, -S-, -SO2-, -C(O)-, -C(O)-O-, -N(RN)-, -NH-C(O)- or a covalent bond; Y3 represents a hydrogen atom or (C1-C6)alkyl radical, optionally substituted with one or more identical or different halogen radicals; RN represents a hydrogen atom or (C1-C6)alkyl radical; Z3 represents a radical with a given formula (see below); Z'3 represents a phenyl radical, optionally substituted with one ore more identical or different substitutes, chosen from -(CH2)P"-V'3-Y'3; V'3 represents -O-; Y'3 represents a hydrogen atom or (C1-C6)alkyl radical; Z"3 represents a hydrogen atom or -(CH2)q-A"3 radical; A"3 represents (C1-C6)alkyl, phenyl or thienyl radical; alkyl or phenyl radical can be optionally substituted with one or more identical or different substitutes, chosen from halogen and -V"3-Y"3; V"3 represents -O-, -C(O)-, -C(O)-O- or a covalent bond; Y"3 represents a hydrogen atom or (C1-C6)alkyl radical; p is an integer from 0 to 6; p' and p" independently represent an integer from 0 to 1; q is an integer from 0 to 2; R4 represents a radical with formula -(CH2)S-R'4; R'4 represents a 5-7- member heterocycloalkyl, containing at least one nitrogen atom and optionally substituted with (C1-C6)alkyl; or a radical with formula -NW4W'4; W4 represents a hydrogen atom; W'4 represents a hydrogen atom; s is an integer from 0 to 6; in racemic or enantiomeric form or any combination of the said forms, or its pharmaceutically acceptable salt. The invention also relates to a method of obtaining a compound in paragraph 1, a pharmaceutical composition based on the said compound and its use in making a medicinal agent.

EFFECT: new benzimidazole derivatives have good affinity to certain subtypes of melanocortin receptors.

26 cl, 8 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a method of obtaining derivatives of N-acetyl-4-hydroxy-2-methyl-5-(5-methylfur-2-yl)-1H-benzo[g]indole with general formula I: Ia-d lla-d I, lla R=H; R1=H, I, llb R=Cl; R1=H, I, llc R=Br; R1=H, I, Ild R-OCH3; I R1=OCH3, characterised by that formation of a furyl-substituted benzo[g]indole basic structure results from opening and re-closing of the annelated furan ring in the corresponding 2-alkyl-4-N,N-diacetylamino-9-(5-methyl-2-furyl)naphthofurans lla-d while boiling them for 1 minute in a 30% hydrogen chloride solution in ethanol.

EFFECT: method reduces resin formation of the reaction mass, allows for obtaining desired products with high output and widens the range of derivatives, which can be used in obtaining anti-inflammatory compounds.

1 cl, 3 tbl, 5 ex

FIELD: chemistry.

SUBSTANCE: new 5-sulphanyl-4H-1,2,4-triazole derivatives of general formula I (meaning of radicals R1-R3 are indicated in the description of the invention), methods of their preparation by liquid-phase parallel synthesis and pharmaceutical composition are claimed.

EFFECT: claimed compounds display high affinity to some subtypes of somostatin receptors of the SST2 and SST5 subtypes and possibility of their usage for treatment of pathological states or diseases involving one or more of the given somostatin receptors

9 cl, 708 ex

FIELD: chemistry.

SUBSTANCE: invention refers to synthesis of [18F]fluororganic compounds ensured by reaction of [18F]fluoride and relevant halogenide or sulphonate with alcoholic vehicle of formula 1 where R1, R2 and R3 represent hydrogen atom or C1-C18 alkyl.

EFFECT: possibility for mild process with low reaction time and high yield.

21 cl, 2 tbl, 27 ex

FIELD: chemistry.

SUBSTANCE: claimed invention relates to compounds of formula (I), their obtaining and application as elastase inhibitors, and can be applied in medicine, where Y = CH; R№ represents H or alkyl; RІ represents phenyl or 5-6-memner heteroaryl, G1 represents phenyl; R5 represents H, halogen, alkyl, CN or fluorinated alkyl; n=1-3; R4 = H; L represents bond, O, NR29 or alkyl; or R4 and L are bound together in such way that group -NR4L- represents 5-7-member asacyclic ring; G2 represents phenyl, 5-6-member heteroaryl, cycloalkyl, C4-7-heterocycle, bicycle from two condensed, bound with direct bond or separated with O atom rings, selected from phenyl, 5-6-member heteroaryl, cycloalkyl or C4-7-heterocycle; or when L does not represent bond, G2 represents H; s = 0-2; R25 represents H, alkyl or cycloalkyl; R29 represents H or alkyl.

EFFECT: obtaining novel biologically active compounds.

10 cl, 95 ex, 1 tbl

FIELD: chemistry.

SUBSTANCE: present invention pertains to a new derivative of cyclic amine or its salts with the following formula (I): (where symbols stand for the following: A: 5-8-member cyclic amine, which may contain a double bond, a bridged structure and may contain substitutes R7-R11 in the ring, or -NH2, -NH(inferior alkyl), -N(inferior alkyl)2 or ) morpholin-1-yl; ring B: benzole, thiophene, furane, pyrrole, 5-7-member cycloalkane or 5-7-member cycloalkene; X1: a bond or inferior alkylene; X2: -(CR12R13)n-, -N(R14)-, -N(R14)CO-, -CON(R14)-, -CO-, -CH(OH)-, -N(R14)- (CR12R13)n-, (CR12R13)n-N(R14)-, -CON(R14)-(CR12R13)n-, -n(R14)CO-(CR12R13)n-, -(CR12R13)n-N(R14)CO-, -(CR12R13)n-CON(R14)-, -CO-(CR12R13)n- or -(CR12R13)n-CO-; Y1: -OH, -O-inferior alkyl, NH2 or -N3; R1 and R2: are identical or different and stand for a halogen atom, inferior alkyl or inferior alkylene-OH; R3-R6: are identical or different and stand for a hydrogen atom, a halogen atom, inferior alkyl, inferior alkenyl, inferior alkynyl, -O-inferior alkyl, -OH, -NH2, -NH(inferior alkyl), -N(inferior alkyl)2, -NH-CO- inferior alkyl, -N(inferior alkyl)-CO- inferior alkyl, -CN-, -NO2, -CF3, -O-inferior alkylene-OH, -inferior alkylene-OH, -inferior alkylene-halogen, -inferior alkylene-O-inferior alkyl, -CO-5-8-member cyclic amine, -COOH-inferior alkyl, -COO-inferior alkylene-aryl, pyridine, thiophene, -inferior alkylene-morpholine, aryl, which may contain a substitute: -O-inferior alkyl or -CF3; R7: hydrogen atom, inferior alkyl, -inferior alkylene-aryl or -inferior alkylene-pyridine: R7 is substitute on the nitrogen atom of the cyclic amine; R8-R14: are identical or different and stand for a hydrogen atom or inferior alkyl; n: is an integer, equal to 1, 2 or 3; where R5 and R6, R4 and R5 or R3 and R4 can form an inferior alkylene together, -O-inferior alkylene-O-, -O-inferior alkylene-, -inferior alkylene-O-, -C(R15)=C(R16)-O-, -O-C(R15)=C(R16)-, -C(R15)=C(R16)-C(R17)=C(R18)-; R3 and Y1 together can form -O-inferior alkylene-O- or -inferior alkylene-O-; R1 and Y1 together can form -inferior alkylene-O-; and Y1 and a branch on - X1-A together can form -O- or -O-inferior alkylene; R15-R18 stand for a hydrogen atom, under the condition that, 6-chloro-2,2-dimethyl-1-(1-methyl-4-piperidinyl)indan-1-ol is not included in the group of compounds). The invention also pertains to a derivative of cyclic amine or its salts with formula (II), to a derivative of cyclic amine or its salts with formula (III), to pharmaceutical composition, as well as their use.

EFFECT: obtaining new biologically active compounds and pharmaceutical compositions based on these compounds, with antagonist effect on NMDA receptors NMDA.

7 cl, 160 ex, 45 tbl

FIELD: chemistry.

SUBSTANCE: invention claims derivatives of pyridazin-3(2H)-one of formula (I), where R1, R2 and R4 are organic radicals described in the claim 1, R3 is cyclic group described in the claim, and R5 is phenyl or heteroaryl group described in the claim. Compounds of formula (I) inhibit phosphodiesterase 4 (PDE-4) and can be applied in treatment of various diseases or pathological states alleviated by PDE-4 inhibition, and in medicine production for treatment of aforesaid diseases. Also invention claims method of obtaining these compounds and intermediate compounds for their obtainment.

EFFECT: obtaining compounds which can be used in treatment of various diseases or pathological states and in medicine production for treatment of aforesaid diseases.

25 cl, 28 tbl, 243 ex

FIELD: chemistry, pharmaceutics.

SUBSTANCE: claimed invention relates to application of indazole derivatives of general formula (I) , in which: R stands for O; R3 stands for radical (C1-C6)-alkyl, (C2-C6)-alkenyl, (C2-C6)-alkinyl, said radicals being unsubstituted or substituted with one or several substitutes, given in item 1 of the formula; R4, R5, R6 and R7, independently on each other are selected from following radicals; hydrogen atom, halogen, CN, NO2, NH2, NHSO2R9, trifluoromethyl, trifluoromethoxygroup, (C1-C6)-alkyl, phenyl, phenyl-(C1-C6)-alkyl, pyridyl, possibly substituted with amino or hydroxygroup, thienyl, furanyl, morpholino, phenyl being unsubstituted or substituted with one or several substitutes, given in item 1 of the formula; R8, R9, R10, R11, independently on each other, stand for hydrogen atom, (C1-C6)-alkyl, phenyl possibly substituted with halogen; their racemates, enantiomers, diastereoisomers and their mixtures, their tautomers and their pharmaceutically acceptable salts for obtaining medication, inhibiting phosphorylation of Tau-protein. Invention also relates to novel compounds of formula (I), particular indazole derivatives, their racemates, enantiomers, tautomers and pharmaceutically acceptable salts, pharmaceutical composition and based on them medication which inhibits Tau-protein phosphorylation, as well as to method of obtaining compounds of formula (I).

EFFECT: obtaining medication based on indazole derivatives, inhibiting Tau-protein phosphorylation.

9 cl, 118 ex, 3 ex

FIELD: medicine.

SUBSTANCE: present invention concerns application of new biologically active substances of the general formula of 1 either their racemates, or their optical isomers, or their pharmaceutically comprehensible salts and-or hydrates, and also to a pharmaceutical composition and its use at manufacturing of the medicinal preparations applied to treatment and-or preventive maintenance of diseases, caused by flu viruses. In compounds of the general formula 1, R1 are represented by the substituent to the amino group chosen from unessentially replaced C1-C6alkyl, unessentially replaced aryl or unessentially replaced 5-6 term azaheterocycl, R14 and R24 independently from each other represent the substituent to an amino group chosen from hydrogen, unessentially replaced C1-C6alkyl, unessentially replaced C3-C8cycloalkyl, or R14 and R24, together with atom of nitrogen to which they are bound, form through R14 and R24 unessentially replaced 5-6-term azaheterocycl with 1-3 heteroatoms in a ring and which can be monocyclic or condensed with a benzene ring, or aminoethanamidine; R2 is a substituent chosen from hydrogen, of unessentially replaced mercapto group, unessentially replaced amino group, unessentially replaced hydroxyl represents alkyn; R3 represents the lowest alkyl; R5 the substituent to the cyclic system chosen from hydrogen, atom of halogen, cyano group, unessentially replaced aryl or unessentially replaced 5-6-term heterocycl represents, the containing 1-2 heteroatoms chosen from nitrogen, oxygen or sulphur and which can be monocyclic or condensed with a benzene ring.

EFFECT: invention provides increase of efficiency of a composition and a method of treatment.

11 cl, 1 dwg, 2 tbl, 5 ex

FIELD: chemistry.

SUBSTANCE: invention refers to new compounds for cyclin-dependent kinase inhibition, in particular, chromenone derivatives by formula Ic: (la) where R1, R2, R3, R4, R5, R6, R7 and A take on values specified in formula of invention. Invention also refers to technology of these compounds, as well as to application of these compounds for medicines intended for cyclin-dependent kinase inhibition and cell proliferation inhibition, used for treatment and prevention of various proliferative diseases. Invention also concerns compositions containing these compounds alone or in combination with other active agent, mixed or otherwise reacted with inert carrier, in particular, pharmaceutical compositions containing these compounds alone or in combination with other active agent, together with pharmaceutically acceptable carriers and adjuvants.

EFFECT: production of new compounds for cyclin-dependent kinase inhibition used for cyclin-dependent kinase inhibition and cell proliferation inhibition used for treatment and prevention of various proliferative diseases.

21 cl, 6 dwg, 2 tbl, 149 ex

FIELD: chemistry.

SUBSTANCE: present invention refers to the new compounds of formula (I): whereat R1 is -SO2NR102R103, -NR101SO2R104 or -COOR105 whereat R101 is hydrogen atom, R102 and R103 each independently represents hydrogen atom or C1-4 alkyl, R104 is C1-4 alkyl and R105 is hydrogen atom or C1-4 alkyl ; X is bond, -CH2- or -O-; Y is -CH2-; ring A and ring B, which are same or different, each independently is benzene, pyridine, pyrazol or piperidine which can have the following substituents: C1-4 alkyl or halogen; ring D is piperidine; R2 is whereat the arrow shows the position of the bond with the ring D; R51 is (1) hydrogen atom a, (2) C1-6alkyl, which can have the following substituents: (a) hydroxy, (b) methoxy, (c) cyano, (d) carboxy, (e) halogen, (f) methyl sulphonylamino, (g) C3-8cycloalkyl or phenyl, which can have the following substituents: methyl, halogen, hydroxy or methoxy, (h) thienyl, pyrazolyl, tetrahydropyranyl, thiazolyl, isooxalyl, imidazolyl, tetraazolyl, pyridyl, pyrimidinyl which can have the following substituents: methyl, trifluoromethyl or hydroxy, (3) C2-10alkenyl, (4) C2-10alkynyl, (5) phenyl which can have the following substituents: C1-4alkyl or halogen, or (6) pyridine or tetrahydropyran; R52 is (1) hydrogen atom a, (2) C1-6alkyl which can have the following substituents: (a) hydroxy, (b) methoxy, (c) carboxy, (d) C3-8cycloalkyl, (e) phenyl or (f) oxo, (3) C3-8cycloalkyl or phenyl which can have the following substituents: C1-4alkyl, hydroxy, cyano, oxo, carbamoyl, N-methyl aminocarbonyl, carboxy, halogen, methoxy, trifluoromethoxy, methythio, methylsulphonyl, acetylamino, dimethylamino, acetyl, tetraazolyl, trifluoromethyl or methylsulphonylamino (4) C3-10cycloalkenyl, (5) adamantyl, (6) thienyl, pyrazolyl, tetrahydropyranyl, isoxaazolyl, isothiazolyl, thiadiazolyl, piperidinyl, pyridyl, pyrimidinyl, pyridazinyl, quinolyl, indolyl, benzothiazolyl, benzoisothiazolyl, benzotriazolyl, dioxaindanyl, benzodioxaindanyl which can have the following substituents: C1-4alkyl, hydroxy, oxo, halogen, azido or trifluoromethyl or (7) benzyloxy groups; and R53 is hydrogen atom or C1-6alkyl; to its salts or its solvates. The invention refers also to the regulator CCR5, to the agent of prevention and/or treatment of HIV infection, immunological or inflammatory diseases, to the pharmaceutical composition, to the medicinal preparation, to the method of disease treatment or prevention as well as to the application of compound as in claim 1.

EFFECT: obtaining of new bioactive compounds possessing anti CCR5 receptor activity.

23 cl, 41 ex

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