Derivatives of peptides comprising thiazepine group for treatment of hyperglycemic states

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to compounds of the formula (I): wherein R1 and R2 are chosen independently from (C1-C4)-alkyl; R3 represents hydrogen atom or hydroxy-group; R4 represents (C1-C4)-alkyl; R5 represents hydroxy-group, or to its pharmaceutically acceptable salts, esters or amides. Also, invention relates to using these compounds as inhibitors of bile acids transfer in ileum for treatment of hyperlipemia. Also, invention describes methods for synthesis of these compounds and pharmaceutical compositions comprising thereof.

EFFECT: improved methods of synthesis, valuable medicinal properties of compounds and pharmaceutical composition.

12 cl, 2 ex

 

The text descriptions are given in facsimile form.

1. The compound of formula (I)

in which R1and R2independently selected from C1-C4-alkyl;

R3represents hydrogen or hydroxy;

R4represents a C1-C4-alkyl;

R5represents hydroxy;

or its pharmaceutically acceptable salt, ester or amide.

2. The compound of formula (I) according to claim 1, in which R1and R2both are butyl; or its pharmaceutically acceptable salt, ester or amide.

3. The compound of formula (I) according to claim 1, in which one of R1and R2represents ethyl, and the other represents a butyl; or its pharmaceutically acceptable salt, ester or amide.

4. The compound of formula (I) according to claim 1, in which R4selected from methyl and ethyl; or its pharmaceutically acceptable salt, ester or amide.

5. The compound of formula (I') according to claim 1

in which R4represents a C1-C2-alkyl, and R3represents hydrogen or hydroxy; or pharmaceutically when mlama salt, ester or amide.

6. The compound of formula (I) according to claim 1, selected from

1,1-dioxo-3,3-dibutil-5-phenyl-7-methylthio-8-(N-{(R)-α-[N'-((S)-1-carboxyethyl)carbarnoyl]benzyl}carbamoylphenoxy)-2,3,4,5-tetrahydro-1,5-benzothiazepine;

1,1-dioxo-3,3-dibutil-5-phenyl-7-methylthio-8-(N-{(R)-α-[N'-((S)-1-carboxypropyl)carbarnoyl]benzyl}carbamoylphenoxy)-2,3,4,5-tetrahydro-1,5-benzothiazepine;

1,1-dioxo-3,3-dibutil-5-phenyl-7-methylthio-8-(N-{(R)-α-[N'-((S)-1-carboxybutyl)carbarnoyl]benzyl}carbamoylphenoxy)-2,3,4,5-tetrahydro-1,5-benzothiazepine;

1,1-dioxo-3,3-dibutil-5-phenyl-7-methylthio-8-(N-{(R)-α-[N'-((S)-1-carboxy-2-methylpropyl)carbarnoyl]benzyl}carbamoylphenoxy)-2,3,4,5-tetrahydro-1,5-benzothiazepine;

1,1-dioxo-3,3-Dibutil-5-phenyl-7-methylthio-8-(N-{(R)-α-[N'-({S)-1-carboxy-2-methylbutyl)carbarnoyl]benzyl}carbamoylphenoxy)-2,3,4,5-tetrahydro-1,5-benzothiazepine;

1,1-dioxo-3,3-dibutil-5-phenyl-7-methylthio-8-(N-{(R)-α-[N'-((S)-1-carboxy-3-methylbutyl)carbarnoyl]benzyl}carbamoylphenoxy)-2,3,4,5-tetrahydro-1,5-benzothiazepine;

1,1-dioxo-3,3-dibutil-5-phenyl-7-methylthio-8-(N'{(R)-α-[N'-((S)-1-carboxy-2-hydroxypropyl)carbarnoyl]benzyl}carbamoylphenoxy)-2,3,4,5-tetrahydro-1,5-benzothiazepine;

1,1-dioxo-3,3-dibutil-5-phenyl-7-methylthio-8-(N'-{(R)-α-[N'-((S')-1-carboxy-2-methylethyl)carbarnoyl]benzyl}carbamoylphenoxy)-2,3,4,5-tetrahydro-1,5-benzothiazepine;

1,1-is ioxo-3,3-dibutil-5-phenyl-7-methylthio-8-(N-{(R)-α -[N'-((S)-1-carboxy-3-methylsulfinylpropyl)carbarnoyl]benzyl}carbamoylphenoxy)-2,3,4,5-tetrahydro-1,5-benzothiazepine;

1,1-dioxo-3,3-dibutil-5-phenyl-7-methylthio-8-(N-{(R)-α-[N'-((S)-1-carboxy-3-methylpropyl)carbarnoyl]benzyl}carbamoylphenoxy)-2,3,4,5-tetrahydro-1,5-benzothiazepine;

1,1-dioxo-3,3-dibutil-5-phenyl-7-methylthio-8-(N-{(R)-α-[N'-((S)-1-carboxyethyl)carbarnoyl]-4-hydroxybenzyl} carbamoylphenoxy)-2,3,4,5-tetrahydro-1,5-benzothiazepine;

1,1-dioxo-3,3-dibutil-5-phenyl-7-methylthio-8-(N-{(R)-α-[N'-((S)-1-carboxypropyl)carbarnoyl]-4-hydroxybenzyl}carbamoylphenoxy)-2,3,4,5-tetrahydro-1,5-benzothiazepine;

1,1-dioxo-3,3-dibutil-5-phenyl-7-methylthio-8-(N-{(R)-α-[N'-((S)-1-carboxybutyl)carbarnoyl]-4-hydroxybenzyl} carbamoylphenoxy)-2,3,4,5-tetrahydro-1,5-benzothiazepine;

1,1-dioxo-3,3-dibutil-5-phenyl-7-methylthio-8-(N-{(R)-α-[N'-((S)-1-carboxy-2-methylpropyl)carbarnoyl]-4-hydroxybenzyl}carbamoylphenoxy)-2,3,4,5-tetrahydro-1,5-benzothiazepine;

1,1-dioxo-3,3-dibutil-5-phenyl-7-methylthio-8-(N-{(R)-α-[N'-((S)-1-carboxy-2-methylbutyl)carbarnoyl]-4-hydroxybenzyl} carbamoylphenoxy)-2,3,4,5-tetrahydro-1,5-benzothiazepine;

1,1-dioxo-3,3-dibutil-5-phenyl-7-methylthio-8-(N-{(R)-α-[N'-((S)-1-carboxy-3-methylbutyl)carbarnoyl]-4-hydroxybenzyl}carbamoylphenoxy)-2,3,4,5-tetrahydro-1,5-benzothiazepine;

1,1-dioxo-3,3-dibutil-5-phenyl-7-methylthio-8-(N-{(R)-α-[N'-((S)-1-CT is hydroxy-2-hydroxyethyl)carbarnoyl]-4-hydroxybenzyl}carbamoylphenoxy)-2,3,4,5-tetrahydro-1,5-benzothiazepine;

1,1-dioxo-3,3-dibutil-5-phenyl-7-methylthio-8-(N-{(R)-α-[N'-((S)-1-carboxy-2-hydroxypropyl)carbarnoyl]-4-hydroxybenzyl}carbamoylphenoxy)-2,3,4,5-tetrahydro-1,5-benzothiazepine;

1,1-dioxo-3,3-dibutil-5-phenyl-7-methylthio-8-(N-{(R)-α-[N'-((S)-1-carboxy-2-methylthioethyl)carbarnoyl]-4-hydroxybenzyl}carbamoylphenoxy)-2,3,4,5-tetrahydro-1,5-benzothiazepine;

1,1-dioxo-3,3-dibutil-5-phenyl-7-methylthio-8-(N-{(R)-α-[N'-((S)-1-carboxy-2-methylsulfinylphenyl)carbarnoyl]-4-hydroxybenzyl}carbamoylphenoxy)-2,3,4,5-tetrahydro-1,5-benzothiazepine;

1,1-dioxo-3,3-dibutil-5-phenyl-7-methylthio-8-(N-{(R)-α-[N'-((S)-1-carboxy-2-methylethyl)carbarnoyl]-4-hydroxybenzyl}carbamoylphenoxy)-2,3,4,5-tetrahydro-1,5-benzothiazepine;

1,1-dioxo-3,3-dibutil-5-phenyl-7-methylthio-8-(N-{(R)-α-[N'-((S)-1-carboxy-2-methoxyethyl)carbarnoyl]-4-hydroxybenzyl} carbamoylphenoxy)-2,3,4,5-tetrahydro-1,5-benzothiazepine;

1,1-dioxo-3,3-dibutil-5-phenyl-7-methylthio-8-(N-{(R)-α-[N'-((S')-1-carboxy-3-metaltipped)carbarnoyl]-4-hydroxybenzyl}carbamoylphenoxy)-2,3,4,5-tetrahydro-1,5-benzothiazepine;

1,1-dioxo-3,3-dibutil-5-phenyl-7-methylthio-8-(N-{(R)-α-[N'-((S)-1-carboxy-3-methylsulfinylpropyl)carbarnoyl]-4-hydroxybenzyl}carbamoylphenoxy)-2,3,4,5-tetrahydro-1,5-benzothiazepine;

1,1-dioxo-3,3-dibutil-5-phenyl-7-methylthio-8-(N-{(R)-α-[N'-((S)-1-carboxy-3-methylpropyl)carbarnoyl]-4-hydroxybenzyl}ka is Samoletov)-2,3,4,5-tetrahydro-1,5-benzothiazepine,

or its pharmaceutically acceptable salt of ester or amide.

7. The method of obtaining the compounds of formula (I) or its pharmaceutically acceptable salt of ester or amide, which includes the interaction of the acid of formula (VII)

where R1, R2and R3unless otherwise specified, have the meanings defined in claim 1, or its activated derivative;

with an amine of formula (VIII)

where R4and R5unless otherwise specified, have the meanings defined in claim 1, and then, if necessary or desirable:

i) the conversion of compounds of formula (I) into another compound of formula (I);

ii) removing any protective groups;

iii) formation of pharmaceutically acceptable salt of ester or amide.

8. The compound of formula (I)or its pharmaceutically acceptable salt, ester or amide according to any one of claims 1 to 6, for use as a drug intended for use for inhibiting transfer of bile acids in the ileum (IBAT).

9. The compound of formula (I) or its pharmaceutically acceptable salt, ester or amide according to any one of claims 1 to 6, for use in the method of the prophylaxis or therapeutic treatment of painful conditions associated with hyperlipemia the conditions in warm-blooded animal, such as people.

10. The use of the compounds of formula (I) or its pharmaceutically acceptable salt of ester or amide according to any one of claims 1 to 6 for preparing a medicinal product for use for inhibiting transfer of bile acids in the ileum (IBAT) in a warm-blooded animal such as man.

11. Method of inhibiting migration of bile acids in the ileum (IBAT) in a warm-blooded animal such as man that is in need of such treatment, comprising the introduction of a specified animal an effective amount of the compounds of formula (I) or its pharmaceutically acceptable salt of ester or amide according to any one of claims 1 to 6.

12. The pharmaceutical composition inhibiting the transfer of bile acids in the ileum (IBAT), which contains a compound of the formula (I) or its pharmaceutically acceptable salt, ester or amide according to any one of claims 1 to 6, in combination with a pharmaceutically acceptable diluent or carrier.



 

Same patents:

FIELD: synthesis of biologically active compounds.

SUBSTANCE: invention provides 1,5-benzothiazepines of general formula I (formulae presented below), in which Rv and Rw are independently selected from hydrogen and C1-C5-alkyl; one of Rx and Ry represents hydrogen or C1-C6-alkyl and the other hydroxy or C1-C6-alkoxy; Rz is selected from halogen, nitro, cyano, hydroxy, amino, carboxy, carbamoyl, mercapto, sulfamoyl, C1-C6-alkyl, and other residues indicated in claim 1 of invention; v is a number from 0 to 5; one of R4 and R5 represents group of general formula IA; R3 and R6 and the second from R4 and R5 are independently selected from hydrogen, halogen, nitro, cyano, hydroxy, amino, carboxy, carbamoyl, mercapto, sulfamoyl, C1-C6-alkyl, and other residues indicated in claim 1; R3 and R6 and the second from R4 and R5 being optionally substituted by one or several R16 groups at their carbon atoms; D represents -O-, -N(Ra)-, -S(O)b- or -CH(Ra)-, wherein Ra is hydrogen or C1-C6-alkyl; and b=0-2; ring A represents aryl or heteroaryl and is optionally substituted by one or several substituents selected from R17; R7 represents hydrogen, C1-C4-alkyl, carbocyclyl, or heterocyclyl and is optionally substituted by one or several substituents selected from R18; R8 represents hydrogen or C1-C4-alkyl; R9 represents hydrogen or C1-C4-alkyl; R10 represents hydrogen or C1-C4-alkyl, carbocyclyl, or heterocyclyl and is optionally substituted by one or several substituents selected from R19; R11 represents carboxy, sulfo, sulfino, phosphono, tetrazolyl, -P(O)(ORc)(ORd), -P(O)(OH)(ORc), -P(O)(OH)(Rd), or -(O)(ORc)(Rd), wherein Rc and Rd are independently selected from C1-C6-alkyl; or R11 represents group of general formula IB, in which X is -N(Rq)-, N(Rq)C(O)-, -O-, or -S(O)a, wherein a=0-2; and Rq is hydrogen or C1-C4-alkyl; R12 represents hydrogen or C1-C4-alkyl; R13 and R14 are independently selected from hydrogen, C1-C4-alkyl, carbocyclyl, heterocyclyl, or R23, of which C1-C4-alkyl, carbocyclyl, heterocyclyl, or R23 can be optionally independently substituted by one or several substituents selected from R20; R15 represents carboxy, sulfo, sulfino, phosphono, tetrazolyl, -P(O)(ORe)(ORf), -P(O)(OH)(ORe), -P(O)(OH)(Re), or -P(O)(ORe)(Rf), wherein Re and Rf are independently selected from C1-C6-alkyl; or R15 represents group of general formula IC, in which R24 is selected from hydrogen and C1-C4-alkyl; R24 is selected from hydrogen, C1-C4-alkyl carbocyclyl, heterocyclyl, and R27, of which C1-C4-alkyl, carbocyclyl, heterocyclyl, or R27 can be optionally independently substituted by one or several substituents selected from R28; R26 is selected from carboxy, sulfo, sulfino, phosphono, tetrazolyl, -P(O)(ORg)(ORh), -P(O)(OH)(ORg), -P(O)(OH)(Rg), or -P(O)(ORg)(Rh), wherein Rg and Rg are independently selected from C1-C6-alkyl; p=1-3; wherein meanings for R13 can be the same or different; q=0-1; r=0-3; wherein meanings for R14 can be the same or different; m=0-2; wherein meanings for R10 can be the same or different; n=1-3; wherein meanings for R7 can be the same or different; z=0-3; wherein meanings for R25 can be the same or different; R16, R17, and R18 are independently selected from halogen, nitro, cyano, hydroxy, carbamoyl, mercapto, sulfamoyl, C1-C4-alkyl, C2-C4-alkenyl, C2-C4-alkynyl, C1-C4-alkoxy, C1-C4-alkanoyl, C1-C4-alkanoyloxy, N-(C1-C4-alkyl)amino, N,N-(di-C1-C4-alkyl)amino, C1-C4-alkyl-S(O)a (wherein a=0-2), C1-C4-alkoxycarbonyl, N-(C1-C4-alkyl)sulfamoyl, and N,N-(di-C1-C4-alkyl)sulfamoyl; wherein R16, R17, and R18 can be optionally independently substituted by one or several of R21 at their carbon atoms; R19, R20, R23, R27, and R28 are independently selected from halogen, nitro, cyano, hydroxy, carbamoyl, mercapto, sulfamoyl, C1-C4-alkyl, C2-C4-alkenyl, C2-C4-alkynyl, C1-C4-alkoxy, C1-C4-alkanoyl, C1-C4-alkanoyloxy, N-(C1-C4-alkyl)amino, N.N-(di-C1-C4-alkyl)amino, C1-C4-alkanoylamino, N-(C1-C4-alkyl)carbamoyl, N,N-(di-C1-C4-alkyl)carbamoyl, C1-C4-alkyl-S(O)a (wherein a=0-2), C1-C4-alkoxycarbonyl, N-(C1-C4-alkyl)sulfamoyl, N,N-(di-C1-C4-alkyl)sulfamoyl, carbocyclyl, heterocyclyl, sulfo, sulfino, amidino, phosphono, -P(O)(ORa)(ORb), -P(O)(OH)(ORa), -P(O)(OH)(Ra), or -P(O)(ORa)(Rb), wherein Ra and Rb are independently selected from C1-C6-alkyl and wherein R19, R20, R23, R27, and R28 can be optionally independently substituted by one or several of R22 at their carbon atoms; R21 and R22 are independently selected from halogen, hydroxy, cyano, carbamoyl, mercapto, sulfamoyl, trifluoromethyl, trifluoromethoxy, methyl, ethyl, methoxy, ethoxy, vinyl, allyl, ethynyl, methoxycarbonyl, formyl, acetyl, formamido, acetylamino, acetoxy, methylamino, dimethylamino, N-methylcarbamoyl, N,N-dimethylcarbamoyl, methylthio, methylsulfinyl, mesyl, N-methylsulfamoyl, N,N-dimethylsulfamoyl; or pharmaceutically acceptable salt thereof, solvate, or salt solvate. Described are also method for preparing compounds of formula I, pharmaceutical compositions based on compounds I, and a method for achieving inhibiting effect relative to interscapular brown adipose tissue (IBAT), and intermediates. (I), (IA), (IB), (IC).

EFFECT: expanded synthetic possibilities in the 1,5-benzothiazepine series.

36 cl, 121 ex

The invention relates to substituted derivatives of propanolamine with bile acids of formula I and their pharmaceutically acceptable salts and physiologically functional derivatives, where GS is a group of the bile acid of the formula II, R1connection with X, HE, R2connection with X, HE, -O-(C1-C6)alkyl, -NH-(C2-C6)-alkyl-SO3N, -NH-(C1-C6)-alkyl-COOH, R1and R2at the same time does not mean the relationship with X, X -

l,m, n- 0,1; L - (C1-C6)-alkyl, AA1, AA2independently amino acid residue, may be one - or multi-substituted amino group

Thrombin inhibitors // 2178796

The invention relates to medicine, namely to methods of producing biologically active substances with immunoregulatory properties, and may find application in medicine,veterinary medicine and experimental biochemistry

The invention relates to medicine, namely to methods of producing biologically active substances with immunoregulatory properties, and may find application in medicine, veterinary medicine and experimental biochemistry

The invention relates to new N-(-substituted pyridinyl)caronel-dipeptides, which have activity as inhibitors of the enzyme that promotes the conversion of angiotensin
The invention relates to a method of crystallization by cooling methyl ester of alpha-L-aspartyl-L-phenylalanine (hereinafter AWS), which is likely to find wide application as a low-calorie zacharopoulou substance because it has the sweetness of high quality and is approximately 200 times sweeter than sugar

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel indolyl-derivatives of the formula (I): and their pharmaceutically acceptable salts and esters wherein R1 means phenyl optionally substituted with from one to three substitutes chosen independently from halogen atom, (C1-C8)-alkyl, (C1-C8)-alkoxy-group and (C1-C8)-alkyl substituted with from one to three halogen atoms; R2 means hydrogen atom, (C1-C8)-alkyl; R3 means (C1-C8)-alkoxy-group; R4 means hydrogen atom; A means oxygen atom or sulfur atom; n = 1,2 or 3. Synthesized compounds possess agonistic activity with respect to PPARα- and/or PPARγ-receptors. Also, invention relates to methods for their synthesis, a pharmaceutical composition based on thereof and their using for preparing medicinal agents, and to a method for treatment and/or prophylaxis of diseases.

EFFECT: improved method of synthesis and treatment, valuable medicinal properties of compounds and pharmaceutical composition.

29 cl, 1 tbl, 7 sch, 17 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel crystalline forms of [R-(R*,R*)]-2-(4-fluorophenyl)-β,δ-dihydroxy-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrol-1-heptanic acid (free form of atorvastatin) designated as forms A and B. These forms are characterized by powdery roentgenogram and NMR spectra of solid bodies. Also, invention elates to pharmaceutical compositions based on these forms and to a method for treatment of hyperlipidemia and hypercholesterolemia, osteoporosis, prostate benign hyperplasia and Alzheimer's disease.

EFFECT: valuable medicinal properties of forms and pharmaceutical compositions.

14 cl, 6 tbl, 4 dwg, 1 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention describes cyclic-substituted diphenylazethidinones of the formula (I): wherein each radical among R1, R2, R3, R4, R5 and R6 means independently of one another (C1-C30)-alkylene-(LAG)n wherein n = 1-2; one or two carbon atoms in alkylene residue are replaced with phenyl or piperazinyl residues or (C3-C10)-cycloalkyl residue; one or some carbon atoms in alkylene residue can be replaced with -S(O)n wherein n = 2; -O-, -(C=O)- or -NH-; hydrogen atom (H), fluorine atom (F), chlorine atom (Cl), bromine atom (Br), iodine atom (J), O-(C1-C6)-alkyl; (LAG)n means mono- or tricyclic trialkyl ammoniumalkyl residue, -(CH2)0-SO3H, -(CH2)0-COOH, -(CH2)0-C(=NH)(NH2), and pharmaceutically acceptable salts also. Proposed compounds decrease the serum cholesterol content. Also, invention describes using these compounds for preparing a medicinal agent used in treatment of lipid metabolism disorders.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.

7 cl, 1 tbl, 22 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention describes compounds of the formula (I): wherein R1-R5 mean independently of one another (C0-C30)-alkylene-(LAG)n wherein n = 1, and one or some C-atoms in alkylene residue can be replaced for -O-, -(C=O)-, -C=CH-, -NH-, hydrogen atom (H), fluorine atom (F), chlorine atom (Cl), bromine atom (Br), iodine atom (J), (C1-C6)-alkyl, O-(C1-C6)-alkyl; (LAG)n means mono- or tricyclic trialkyl ammoniumalkyl residue or LAG can mean -(CH2)0-10-C(=NH)(NH2), -(CH2)0-10-C(=NH)(NHOH) or -NR7-C(=NR8)(NR9R10). Also, invention describes a medicinal agent for decreasing the serum cholesterol content and a method for its preparing. Proposed compounds are useful, for example, as hypolipidemic agents.

EFFECT: improved methods of synthesis and preparing, valuable medicinal properties of compounds and pharmaceutical composition.

6 cl, 1 tbl, 34 ex

FIELD: chemical-pharmaceutical industry, pharmacy.

SUBSTANCE: invention relates to a solid standard dosed formulation comprising atorvastatin or its pharmaceutically acceptable salt and a vehicle, or combination of vehicles that comprises above 50 wt.-% of diluting agents and less 5 wt.-% of alkaline substance as an additive. Indicated diluting agent represents lactose monohydrate, anhydrous lactose, microcrystalline cellulose or sodium chloride. The solid standard dosed formulation represents a table or capsule that is made without granulation step. Invention provides preventing segregation during making the standard dosed formulation and to provides the high dosing precision of atorvastatin. Excluding the granulation step results to enhancing effectiveness in producing the standard dosed medicinal formulation and without decreasing the rate of production of composition.

EFFECT: improved and valuable properties of compositions.

5 cl, 1 dwg, 3 tbl, 7 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel compounds of the formula (I) and their pharmaceutically acceptable salts. Proposed compounds possess properties of agonists of receptors activated by peroxisome proliferators (PPAR agonists) and can be used in treatment of such diseases as diabetes mellitus, hypertension, atherosclerotic diseases and others. In the general formula (I) R1 means lower alkyl, monocyclic (C3-C6)-cycloalkyl; R2 means hydrogen atom, halogen atom, lower alkyl, lower alkoxy-group wherein at least one of three radicals R3, R4, R5 or R6 is not hydrogen atom; or R3 and R4 are bound together to form a ring with carbon atoms to which they are bound, and R3 and R4 mean in common -CH=CH-S-, -S-CH=CH-, -CH=CH-CH=CH-, and R5 and R6 are given above; R7 means lower alkyl, lower alkenyl; R8 means hydrogen atom or lower alkyl; n = 1, 2 or 3. Also, invention relates to a pharmaceutical composition based on the invention compounds and to using compounds of the invention in preparing medicinal agents used in treatment and/or prophylaxis of diseases mediated by agonists PPARα and/or PPARγ.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.

20 cl, 1 tbl, 13 sch, 71 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel derivatives of aminoalkylpyridines of the general formula (I): wherein n means a whole number from 1 to 4; R1 represents hydrogen atom, hydroxyl group or lower (C1-C6)-alkoxy-group; R2 represents hydrogen atom or lower (C1-C6)-alkyl group with linear or branched chain; X represents hydrogen atom, fluorine atom, chlorine atom, bromine atom, hydroxyl group, trifluoromethyl group, 3,4-di-Cl, 2,4-di-Cl or lower (C1-C6)-alkoxy-group, or salts of these compounds as products of adding physiologically acceptable acid. Also, invention relates to a pharmaceutical composition based on these compounds inhibiting biosynthesis of cholesterol. Also, invention considers using abovementioned compounds in preparing pharmaceutical composition and to a method for synthesis of compounds of the formula (I). Invention provides synthesis of novel compounds possessing valuable biological properties and preparing pharmaceutical composition based on thereof.

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

10 cl, 12 dwg, 5 ex

FIELD: medicine, pharmacy.

SUBSTANCE: invention relates to medicinal agents, namely, to a novel medicinal agent possessing hypolipidemic effect and representing molecular complex of simvastatin with β-glycyrrhizic acid in the mole ratio simvastatin : β-glycyrrhizic acid= 1:(1-4). Proposed complex possess higher effectiveness in lower doses that results to reducing toxicity in treatment.

EFFECT: improved and valuable medicinal properties of agent.

3 dwg, 5 ex

FIELD: organic chemistry, medicine.

SUBSTANCE: invention relates to benzothiadiazepine derivatives of general formula I wherein M represents -N-one of R4 and R5 representsgroum of formula ring A represents aryl; or hydrolysable in vivo pharmaceutically acceptable salts, esters and amides thereof. Such derivatives are useful as inhibitors of bile acid transfer in ileal intestine (IBAT) for hyperlipemia treatment. Methods for production of abovementioned derivatives also are described.

EFFECT: new benzothiadiazepine derivatives for hyperlipemia treatment.

14 cl, 67 ex

FIELD: medicine, gynecology.

SUBSTANCE: the present innovation deals with treating puerperal obesity-manifesting neuroendocrine syndrome. The method includes fractional nutrition, terrencur per 7.8-8.5 km/d, mineral baths and gynecological irrigations at applying hydrocarbonate-sulfate sodium-calcium mineral water of Slavyanovski well of 35-38°. During the whole course of therapy it is necessary to have the intake of the same mineral water thrice daily about 30-40 min before meals. One should carry out acupuncture reflexotherapy due to the second brake method during maximal activity of renal canals, those of urinary bladder, liver and pancreas. Acupuncture reflexotherapy should be alternated according to the days of affecting key points, group LO of "magic meridians", "key points" on the main syndrome. The innovation improves therapeutic result due to affecting autonomic nervous system.

EFFECT: higher efficiency of therapy.

3 ex, 1 tbl

FIELD: biochemistry.

SUBSTANCE: invention relates to dipeptide mimetic selected from glutaminyl thiazolidine or glutaminyl pyrrolodine and salts thereof as well as to using of such compounds in treatment of abnormal glucose tolerance, glucoseuria, diabetes mellitus and other disordered as well as complications associated with diabetes mellitus in mammalians.

EFFECT: new effectors of dipeptidyl peptidase IV.

18 cl, 3 tbl, 2 ex

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