Glp-1 analogs

FIELD: peptides, medicine, pharmacy.

SUBSTANCE: invention relates to novel peptide analogs of glucagons-like peptide-1 and its pharmaceutically acceptable salts that are used in treatment of mammals.

EFFECT: valuable medicinal properties of analogs.

10 cl, 1 tbl, 411 ex

 



 

Same patents:

Glp-1 derivatives // 2214419
The invention relates to a derivative of GLP-1 parent peptide having one or two lipophilic substituent attached optionally via an amino acid or dipeptide spacer to amino acid residue that is not N-terminal or C-terminal amino acid residue, where the parent peptide has the sequence: HAEGTFTSDVSSYLEGQAAKEFIAWLVKGRG, or is in the amount of up to ten amino acid residues are replaced with any-amino acid residue which can be encoded using the genetic code

Analogues of glp-1 // 2214418
The invention relates to peptide analogs glucoheptonate peptide-1 formula

(R2R3)-A7-A8-A9-A10-A11-A12-A13-A14-A15-A16-A17-A18-A19-A20-A21-A22-AND23-AND24-AND25-AND26-AND27-AND28-AND29-AND30-AND31-AND32-AND33-AND34-AND35-AND36-AND37-AND38-AND39-R1the values of the radicals indicated in the claims

Analogues of glp-1 // 2208015
The invention relates to compounds of the formula (R2R3) AND7-AND8-AND9-AND10-AND11-AND12-AND13-AND14-AND15-AND16-AND17-AND18-AND19-AND20-AND21-AND22-AND23-AND24-AND25-AND26-AND27-AND28-AND29-AND30-AND31-AND32-AND33-AND34-AND35-AND36-AND37-R1,

where a7-AND37represent different amino acid residues, the values radicals cm

FIELD: organic chemistry, biochemistry, medicine, pharmacy.

SUBSTANCE: invention proposes compounds of the general formula (1): wherein X is chosen from sulfur atom and methylene group; X1 is chosen from sulfur atom and methylene group; X2 is chosen from oxygen (O), sulfur (S) atoms and methylene group; X3 means -NR5 or carbonyl group; R1 means hydrogen atom or nitrile group; R and R3 are chosen independently from hydrogen atom (H) and (C1-C6)-alkyl; R4 means R4A when X3 means -NR5 and R4B when X3 means carbonyl group; R4A is chosen from -R6R7NC(=O), -R6R7NC(=S), -R8(CH2)qC(=O), -R8(CH2)qC(=S), -R8(CH2)qSO2 and -R8(CH2)qOC(=O); R4B means -R6R7N; R5 means hydrogen atom (H); R6 and R7 are chosen independently from -R8(CH2)q, or they form in common -(CH2)2-Z1-(CH2)2- or -CHR9-X2-CH2-CHR10-; R8 is chosen from hydrogen atom (H), (C1-C4)-alkyl, cycloalkyl group condensed with benzene ring, acyl, dialkylcarbamoyl, dialkylamino-group, N-alkylpiperidyl, optionally substituted aryl, optionally substituted α-alkylbenzyl, optionally substituted aroyl, optionally substituted arylsulfonyl and optionally substituted heteroaryl representing monocyclic 5- and 6-membered ring aromatic group with one or two heteroatoms chosen from nitrogen, oxygen and sulfur atoms, and derivatives of abovementioned rings condensed with benzene; R9 and R10 are chosen independently from hydrogen atom (H), hydroxymethyl and cyanomethyl groups; Z1 is chosen from -(CH2)r-, -O-, and -N((CH2)q)R8)-; Z2 means optionally the substituted ortho-phenylene group; m = 1-3; n = 0-4; p = 2-5; q = 0-3, and r = 1 or 3. Proposed compounds are inhibitors of dipeptidyl-peptidase IV and can be used in preparing pharmaceutical compositions designated for treatment of different diseases, among them, diabetes mellitus of type 2.

EFFECT: valuable medicinal and biochemical properties of compounds and pharmaceutical composition.

22 cl, 8 tbl, 453 ex

FIELD: organic chemistry, medicine, endocrinology.

SUBSTANCE: invention relates to improved methods for modulation of diabetes mellitus type II in mammal and modulation of resistance to insulin. Methods involve administration to indicated mammal needing in this treatment of (-)-stereoisomer of compound of the formula (I): wherein R is chosen from group including hydroxy-, lower araloxy-, d-(lower)-alkylamino-(lower)-alkoxy-, (lower)-alkylamido-(lower)-alkoxy-, benzamido-(lower)-alkoxy-, ureido-(lower)-alkoxy-, N'-(lower)-alkyl-ureido-(lower)-alkoxy-, carbamoyl-(lower)-alkoxy-, halophenoxy-substituted lower alkoxy-, carbamoyl-substituted phenoxy-group; or R represents hydrolysable ester group; each X represents independently halogen atom; or its pharmaceutically acceptable salt wherein (-)-stereoisomer doesn't comprise conceptually (+)-stereoisomer. Also, invention relates to pharmaceutical compositions comprising (-)-stereoisomer of compound of the formula (I) and wherein compositions show significantly reduced inhibitory effect on activity of cytochrome P-450 2C9 as compared with racemic composition having 0% enantiomeric excess of (-)-stereoisomer.

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

59 cl, 21 dwg, 8 tbl, 18 ex

FIELD: medicine, endocrinology, pharmaceutical technology, pharmacy.

SUBSTANCE: invention relates to preparing insulin preparations with the prolonged effect used in therapy of diabetes mellitus. Invention relates to a method for preparing the pharmaceutical composition suspension based on domestic industry genetic engineering (recombinant) human insulin comprising protamine sulfate and insulin in the concentration 100 IU/ml designated for bottling. Method for preparing the pharmaceutical composition based on genetic engineering human insulin in small bottles involves preparing insulin an aqueous suspension in the concentration of insulin 100 IU/ml comprising zinc chloride, protamine sulfate, sodium hydrogen phosphate, glycerol, phenol and meta-cresol additionally, carrying out the sterilizing filtration and crystallization. Method involves preliminary preparing a buffer solution with pH = 8.3-8.5 at stirring comprising 2.4 g/ml of sodium hydrogen phosphate, 1.4-1.6 mg/ml of meta-cresol, 0.5-0.7 mg/ml of phenol, 15-17 mg/ml of glycerol and water. Then method involves preparing insulin solution by successive addition of 0.35-0.45 mg/ml of protamine sulfate, substance of human insulin, 1% aqueous solution of zinc chloride in the content of zinc in the medicinal formulation 0.025-0.035 mg/100 IU of insulin and water acidified to pH = 3.1-3.3. Solutions are subjected for sterilizing filtration and crystallization is carried out before bottling and holding the prepared composition at temperature 12-16°C and stirring for 16-24 h. Invention solves the problem for enhancing effectiveness of the technological process for preparing the pharmaceutical composition suspension. Invention can be used in medicinal industry for preparing the domestic genetic engineering (recombinant) suspension of protamine-human insulin in small bottles.

EFFECT: improved preparing method.

1 tbl, 2 ex

FIELD: medicine, in particular preparation of quick closing insulin preparations for treatment of diabetus mellitus.

SUBSTANCE: claimed method includes preparation of solutions containing insulin and ancillary substances, blending thereof, sterilizing filtration and bottling into flacks. Previously buffer solution containing 2.35-2.45 mg of disubstituted sodium phosphate; 2.25-3.0 mg m-cresol, and 15-17 mg of glycerol as calculated to 100 U of insulin is prepared, then insulin solution is prepared at 3.1-3.3 and added to buffer solution. Solutions are blended at agitation for 10-20 min, pH is adjusted to 7.2-7.4 and water is added up to finish insulin concentration of 100 IU/ml.

EFFECT: human gene engineered insulin of prolonged storage time without losses of physical, chemical and biological properties.

2 ex, 1 tbl

FIELD: medicine.

SUBSTANCE: one should apply anticonvulsive derivatives in mammalians such as topiramate for preventing the development of non-insulin dependent diabetes mellitus and syndrome X, treating and preventing skin diseases associated with these diseases. The innovation suggested enables to prevent increased blood levels of glucose, triglycerides and insulin despite patient's body weight and, thus, avoid the development of the above-mentioned states.

EFFECT: higher efficiency of prophylaxis.

19 cl, 5 ex, 11 tbl

FIELD: medicine, endocrinology.

SUBSTANCE: the present innovation deals with preventing diabetes mellitus and its aftereffects. It is suggested to apply sibutramin and its analogs to decrease non-susceptibility to insulin in diabetes-free patients, prevent decreased tolerance to glucose and decrease the quantity of introduced insulin in diabetes-suffering patients and normalize body weight, as well.

EFFECT: higher efficiency of application.

28 cl, 3 dwg, 1 tbl

The invention relates to new derivatives and analogs 3-arylpropionic acid having the General formula (I), and their stereo and optical isomers and racemates, as well as their pharmaceutically acceptable salts, wherein in the formula And is located in the meta - or para-position and represents a

where: R represents hydrogen;

-ORawhere Rarepresents hydrogen, alkyl, phenyl or alkylphenyl;

-NRaRbwhere Raand Rbare the same or different and represent hydrogen, alkyl, phenyl, alkylphenyl, cyano;

R1represents alkyl, cyano;

-ORewhere Rerepresents alkyl, phenyl or alkylphenyl;

-O-(CH2]m-ORfwhere Rfrepresents alkyl, and m is an integer of 1-2;

-SRdwhere Rdrepresents an alkyl or phenyl;

-SO2ORawhere Rarepresents alkyl, phenyl or alkylphenyl;

-COORdwhere Rdrepresents alkyl;

R2represents hydrogen or alkyl;

R3and R4

D is situated in the ortho-, meta - or para-position and represents a

-OSO2Rdwhere Rdrepresents alkyl, phenyl or alkylphenyl;

-OCONRfRawhere Rfand Rarepresent hydrogen, alkyl, phenyl or alkylphenyl;

-NRcCOORdwhere Rcrepresents hydrogen or alkyl and Rdrepresents alkyl, phenyl or alkylphenyl;

-NRcCORawhere Rcrepresents hydrogen or alkyl, and Rarepresents hydrogen, alkyl, phenyl or alkylphenyl;

-NRcRdwhere Rcand Rdrepresent hydrogen, alkyl, phenyl or alkylphenyl;

-NRcSO2Rdwhere Rcrepresents hydrogen or alkyl, and Rdrepresents alkyl, phenyl or alkylphenyl;

-NRcCONRaRkwhere Rcrepresents hydrogen, Raand Rkare the same or different and each represents hydrogen, alkyl, phenyl or alkylphenyl;

-NRcCSNRaRkwhere Rcrepresents hydrogen, Raand Rkare the same or different and each represents hydrogen, phenyl иLASS="ptx">-SRcwhere Rcrepresents alkyl, phenyl or alkylphenyl;

-SO2ORawhere Rarepresents alkyl, phenyl or alkylphenyl;

-CN;

-CONRcRawhere Rcrepresents hydrogen or alkyl, and Rarepresents hydrogen or alkyl;

D’ is located in the meta-position and represents-ORfwhere Rfrepresents alkyl; or is located in the ortho-, meta - or para-position and represents hydrogen;

D’ is located in the ortho - or para-position and represents-NO2, -ORfwhere Rfrepresents alkyl; or is located in the ortho-, meta - or para-position and represents hydrogen;

where specified, the alkyl means a straight or branched alkyl group having from 1 to 6 carbon atoms, or cyclic alkyl having from 3 to 6 carbon atoms, with the specified alkyl may be substituted by one or more than one group of alkyl, alkoxy, halogen or phenyl; where the specified phenyl may be substituted by one or more than one group of alkyl, alkoxy, nitro, thiol, or halogen; the invention also relates to a method of their production, pharmaceutical preparations containing them, the Sabbath.

The invention relates to new pharmaceutical compositions that contain the basis or agonist of the basis for the treatment of diabetes, slowing of gastric emptying or reduce food intake, and their dosage forms and methods for their introduction
The invention relates to medicine, Hematology, cardiology and endocrinology and can be used for normalization of platelet aggregation in patients with metabolic syndrome

The invention relates to water-soluble unit derived insulin, which remains In 24-B30 of the b-chain derived insulin is sequence Phe-x-X-x-X-x-X, where each X independently represents any amino acid or a deletion of at least one X is Nsubstituted by a lysine residue in which the Deputy is a 5--lithocholic acid or 5--lithocholic acid, connected through the-glutamyl,-glutamyl oror-aspartyl as a linker, where the unit size is defined in the gel-filtration system, more than aldolase, and the Assembly includes at least 2 zinc ions per 6 molecules derived insulin

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel derivatives of pyrimidine of the general formula (I) that possess properties of antagonists to adenosine A2-receptors and can be effective in relieve, for example, of defecation. In compound of the general formula (I) each R1 and R2 represents hydrogen atom; R3 represents hydrogen atom, halogen atom, amino-group, cyano-group, alkyl group comprising 1-6 carbon atoms, alkoxy-group comprising 1-6 carbon atoms, alkenyloxy-group comprising 2-6 carbon atoms, phenyl group that can be substituted with halogen atom, pyridyl group, furyl group or thienyl group; R4 represents pyridyl that can be substituted with a substitute chosen from the group comprising: hydrogen atom, halogen atom, amino-group, mono- or dialkylamino-group, aminoalkylamino-group wherein each has in alkyl residue from 1 to 6 carbon atoms, alkyl group comprising from 1 to 6 carbon atoms that can be substituted with halogen atom, hydroxy-group, amino-group, mono- or dialkylamino-group, alkoxycarbonyl wherein each has in alkyl residue from 1 to 6 carbon atoms, alkoxy-group comprising in alkyl group from 1 to 6 carbon atoms substituted with phenyl or pyridyl, hydroxyalkoxy-group comprising in alkyl residue from 1 to 6 carbon atoms, hydroxycarbonyl, alkoxycarbonyl comprising from 1 to 6 carbon atoms in alkyl residue, alkenyl group comprising from 2 to 6 carbon atoms, alkynyl group comprising from 2 to 6 carbon atoms, piperidinyl group that can be substituted with hydroxyl group, or represents group of the formula (IV): R5 represents phenyl that can be substituted with halogen atom, pyridyl group, thienyl or furyl group.

EFFECT: valuable biological properties of derivatives.

16 cl, 2 tbl, 185 ex

FIELD: organic chemistry, medicine, biochemistry, pharmacy.

SUBSTANCE: invention relates to novel derivatives of 2-cyano-4-fluoropyrrolidine of the formula (I): or its pharmaceutically acceptable salt wherein A represents group of the general formula (II): wherein B represents carbonyl or sulfonyl group; R1 represents (C1-C6)-alkyl that can be optionally substituted with group chosen from the group comprising -OH or atoms of fluorine, chlorine, bromine or iodine, phenyl optionally substituted with -CN or morpholinyl group, or if B represents carbonyl then R1 can mean hydrogen atom; R2 represents (C1-C6)-alkyl optionally substituted with hydroxyl group or hydrogen atom. Compounds of the formula (I) are inhibitors of enzyme dipeptidyl peptidase IV that allows its using in pharmaceutical composition that is designated for treatment of insulin-dependent diabetes mellitus (diabetes of type 1), non-insulin-dependent diabetes mellitus (diabetes of type 2), diseases associated with resistance to insulin or obesity.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.

8 cl, 8 tbl, 11 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel analogs of fatty acids of the general formula (I): R1-[Xi-CH2]n-COOR2 wherein R1 represents (C6-C24)-alkene with one or more double bond, and/or (C6-C24)-alkyne; R2 represents hydrogen atom or (C1-C4)-alkyl; n represents a whole number from 1 to 12; I represents an uneven number and shows position relatively to COOR2; Xi is chosen independently of one another from the group comprising oxygen (O), sulfur (S) and selenium (se) atom and -CH2 under condition that at least one among Xi is not -CH2 and under condition that if R1 represents alkyne then a carbon-carbon triple bond is located between (ω-1)-carbon atom and (ω-2)-carbon atom, or between (ω-2)-carbon atom and (ω-3)-carbon atom, or between (ω-3)-carbon atom and (ω-4)-carbon atom, and to their salts and complexes. The claimed compounds can be used in treatment and/or prophylaxis of X syndrome, obesity, hypertension, hepatic fatty dystrophy, diabetes mellitus, hyperglycemia, hyperinsulinemia and stenosis. Also, invention relates to methods for preparing novel analogs of fatty acids. Also, invention relates to a nutrient composition comprising indicated analogs of fatty acids and to a method for reducing the total body mass or amount of lipid tissue in humans or animals. Invention provides the development of novel fatty acid analogs-base compositions or methods for suppression of stenosis, restenosis or associated disorders as result of proliferation and mobilization of vessel smooth muscle cells after, for example, traumatic damages of vessels during surgery operation in vessels.

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

12 cl, 2 dwg, 7 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: the present insulin solution for peroral intake should be applied for treating patients with diabetes mellitus. The suggested insulin solution consists of water and insulin, additionally, it contains sodium chloride at the following ratio of components, weight%: insulin 0.005-0.02, sodium chloride 0.5-1.0, water - up to 100.0. The innovation provides decreased glucose level in blood of animals in case of peroral intake of the solution up to 40% at insulin dosages being about 10 U/kg animal body weight.

EFFECT: higher efficiency.

12 ex, 1 tbl

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