Folate-polyethylene glycol-dihexadecyl-l-glutamate and method for production thereof

FIELD: chemistry.

SUBSTANCE: invention relates to a folate receptor ligand which is folate-polyethylene glycol-dihexadecyl-L-glutamate of formula and a method for production thereof. This compound exhibits the capacity to direct a nanosystem to target cells and increases the efficiency of transportation systems of antitumour agents since folate receptors are present in large amounts on the surface of tumour cells; also they become more at the later stages of development of the disease.

EFFECT: use of an approach based on click-chemistry principles for synthesis of a folate-targeted derivative provides a unique opportunity for fast and efficient modification of nanosystems.

2 cl

 

The invention relates to the field of Bioorganic chemistry, in particular derivatives of amino acids and peptides belonging to the class of aliphatic diesters and dipeptides containing the remainder of folic acid.

The use of a derivative of folic acid as a ligand folate receptor is a promising direction to increase the effectiveness of anticancer drugs.

Structural components of the folate-polyethylene glycol-dihexadecyl-L-glutamate, are the remains of folic acid, polyethylene glycol and diapir L-glutamic acid.

We know the derivative of folic acid cells of the dspe-PEG-folate in which the lipid fragment of the molecule presents a derivative of phosphatidylethanolamine [H.E.J.Hofland, .Masson, S.Iginla, I.Osetinsky, P.Wils, Molecular Therapy, 2002, V.5, N.6, P.739-744].

The use of cells of the dspe in the molecule contributes to the formation of lipid aggregates. The disadvantage of this compound is its relatively high cytotoxicity, low efficiency and complex synthesis.

Closest to the claimed technical solution is folate-polyethylene glycol-octadecylamine [U.A.Budanova, O.O.Koloskova, Yu.L. Sebyakin, Mendeleev Commun., 2010, N20, P.326-328].

In this connection, the polyethylene glycol with one side connected to the rest of octadecylamine for having exali polymer in the lipid bilayer, but on the other hand - ligand folate receptors for giving nanosystems address function. However, the presence of only one hydrophobic chain in the molecule reduces the interaction with double-stranded lipids in the composition belayneh units.

The technical result of the invention is the creation of a new ligand folate receptors, folate-polyethylene glycol-dihexadecyl-L-glutamate by the reaction of 1,3-dipolar cycloaddition.

Dihexadecyl ester of L-glutamic acid is derived from natural amino acids, so the connection based on it are of low toxicity and high Biodegradability. The application of the principle of "click-chemistry", based on the reaction of 1,3-dipolar cycloaddition allows you to quickly and effectively modify the surface of nanosystems.

To achieve the technical result of the developed method for obtaining compounds, which consists in the interaction of propargylamine dihexadecyl ester of L-glutamic acid O-(β-azithromy)-O-(glycine-N-folate-polyethylene glycol3400with the formation of 1,3-triazole connecting ring.

The implementation of the present invention is confirmed by the example.

Example obtain the intermediate compounds.

To 0.5 g dihexadecyl ester of L-glutamic what acid was added 0.126 g of succinic acid anhydride. After stirring for 10 h was added 0,061 g propargilovyh alcohol in the presence of Vos2O. Propargylamine dihexadecyl ester of L-glutamic acid was isolated by column chromatography in the system toluene-ethyl acetate, 5:1. Output 0,350 g (65%), Rf of 0.75 (toluene-ethyl acetate, 3:1). The mass spectrum of the [M]+: 734,46, (Na+) 756,45, (K+) 774,40.

To 0,175 g of N-(tert-butylcarbamoyl)glycine was added 2,273 g of polyethylene glycol3400in the presence of DCC. The reaction mixture was kept under stirring at 30°C for 36 h O-[glycine-N-(tert-butyloxycarbonyl)]-politiical3400was purified by extraction with methanol-hexane. Output 2,066 g (86,6%), Rf of 0.3 (methylene chloride-ethylacetat-methanol, 7:1:3).1H-NMR spectrum (δ, ppm): 1,42 (t, N, CH3), 3,61 (m, ~N, CH2CH2O), with 3.79 (t, 2H, SOON2), to 3.99 (m, 2H, OCOCH2NH), 4,46 (s, 1H, NH).

To 0,868-[glycine-N-(tert-butyloxycarbonyl)]-poliatilenglikola3400added 0,069 g 3-chloropropanol acid in the presence of DCC. Then added 0,027 g of sodium azide. Then spent processing triperoxonane acid. O-(β-azithromy)-O-(glycine)-polyethylene glycol3400was isolated by preparative chromatography system (chloroform-methanol-water, 6:4:1). Output 0,252 g (85,6%), Rf 0.25 in (toluene-ethyl acetate, 3:1). IR spectrum (film, νmax, cm-1): 3435 (NH), 2870 (CH), 2096 (N3), 1744 (C=O), 1453, 1350, 1298, (CH), 1104 (C-O-C), 952, 843 (CH).

To 0,110 g O-(β)-O-(glycine), poly (ethyleneglycol) 3400added 0,057 g of folic acid in the presence of DCC. The reaction mass pererestorani in chloroform and filtered from unreacted folic acid. Yield 0.04 g (33,1%), Rf of 0.55 (toluene-ethyl acetate, 3:1). In the mass spectrum of MALDI present a set of signals ("comb") of molecular ions O-(β-azithromy)-O-(glycine-N-folate)-poly (ethyleneglycol)3400with a mean of (M+) 3899,69.

Example retrieve the target folate-polyethylene glycol-dihexadecyl-L-glutamate.

To 0.04 g of O-(β-azithromy)-O-(glycine-N-folate)-polietilenglikolya was added 0.008 g dihexadecyl ester of L-glutamic acid. The reaction was carried out in methanol in the presence of catalytic amount of CuI. Output 0,048 g (83.4%of), Rf of 0.35 (chloroform-methanol, 6:1). In the mass spectrum were present set of signals ("comb") of molecular ions folate-polyethylene glycol-dihexadecyl-L-glutamate with a mean of (M+) 4619,15.

The synthesized compound is embedded in liposomes on the basis of dihexadecyl-N-(L-Omnitel)-L-glutamate in an amount of 5%. The particles have a size of 30-40 nm, which is optimal for transport systems. The value of Zeta-potential exceeds 50 mV, resulting in aqueous dispersions occurs electrostatic repulsion of the particles. This in turn leads to the fact that the prepared colloidal solutions are stable for weeks when stored the AI at room temperature.

The use of derivatives of polyethylene glycol as a linker increases hydrophilicity of the outer surface of the bilayer, resulting in the lowering opsonization, receptor-mediated phagocytosis and capture cells of the reticulo-endothelial system.

Designed transport system has a focus on folate receptors. The approach is based on the principles of "click-chemistry", provides the opportunity for fast and efficient modification of nanosystems

Folate-polyethylene glycol-dihexadecyl-L-glutamate

2. The way to obtain folate-polyethylene glycol-dihexadecyl-L-glutamate according to claim 1, which consists in the interaction of propargylamine dihexadecyl ester of L-glutamic acid O-(β-azithromy)-O-(glycine-N-folate-polyethylene glycol3400.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention relates to N-substituted monomers and polymers used in medical devices. Disclosed is a polymer meant for use in implantable medical devices, which contains a plurality of monomer repeating units containing an N-substituted amide of formula (I) where each of X1 and X2 is independently selected from Br and I; each y1 and y2 is independently equal to zero or an integer ranging from 1 to 4, and R1 is selected from substituted or unsubstituted, saturated or unsaturated, straight or branched aliphatic groups containing up to 48 carbon atoms, substituted or unsubstituted aromatic groups containing up to 48 carbon atoms, and substituted or unsubstituted araliphatic groups containing up to 48 carbon atoms, wherein the aliphatic parts are straight or branched and saturated or unsaturated, wherein R1 contains 2-8 heteroatoms selected from O, S and N, where two of the heteroatoms form an amide group of the polymer backbone chain which is an N-substituted C1-C6 alkyl group. Corresponding monomers and versions of use of the disclosed polymer in medicine are also disclosed.

EFFECT: disclosed polymers are characterised by low melt viscosity and can be easily processed without decomposition.

24 cl, 8 ex

FIELD: chemistry.

SUBSTANCE: claimed invention relates to tripticendiole-2,5-based polyhydroxyesters, which can be used as heat-resistant coatings. Said polyhydroxyesters represent compounds of formula: , where n=60-180.

EFFECT: obtained polyhydroxyesters of said structure possess improved heat-resistance, are capable of forming coatings and are well-soluble in polar solvents.

1 tbl

FIELD: chemistry.

SUBSTANCE: claimed invention relates to tripticendiole-2,5-based polyhydroxyesters, which can be used as heat-resistant coatings. Said polyhydroxyesters represent compounds of formula: , where n=60-180.

EFFECT: obtained polyhydroxyesters of said structure possess improved heat-resistance, are capable of forming coatings and are well-soluble in polar solvents.

1 tbl

FIELD: chemistry.

SUBSTANCE: claimed invention relates to tripticendiole-2,5-based polyhydroxyesters, which can be used as heat-resistant coatings. Said polyhydroxyesters represent compounds of formula: , where n=60-180.

EFFECT: obtained polyhydroxyesters of said structure possess improved heat-resistance, are capable of forming coatings and are well-soluble in polar solvents.

1 tbl

FIELD: chemistry.

SUBSTANCE: claimed invention relates to copolyhydroxyesters based on bisphenol A and tripticene diole-2,5, which can be used as film materials with improved heat resistance. Said copolyhydroxyesters represent compounds of formula: , where n=30-100, m= 100-30.

EFFECT: obtained copolyhydroxyesters of said structure possess improved heat resistance, good solubility in polar solvents and film-forming properties.

1 tbl, 3 ex

FIELD: chemistry.

SUBSTANCE: claimed invention relates to copolyhydroxyesters based on bisphenol A and tripticene diole-2,5, which can be used as film materials with improved heat resistance. Said copolyhydroxyesters represent compounds of formula: , where n=30-100, m= 100-30.

EFFECT: obtained copolyhydroxyesters of said structure possess improved heat resistance, good solubility in polar solvents and film-forming properties.

1 tbl, 3 ex

FIELD: chemistry.

SUBSTANCE: claimed invention relates to copolyhydroxyesters based on bisphenol A and tripticene diole-2,5, which can be used as film materials with improved heat resistance. Said copolyhydroxyesters represent compounds of formula: , where n=30-100, m= 100-30.

EFFECT: obtained copolyhydroxyesters of said structure possess improved heat resistance, good solubility in polar solvents and film-forming properties.

1 tbl, 3 ex

FIELD: chemistry.

SUBSTANCE: invention relates to method of obtaining polyalkyleneglycol esters of α-tocoferol, applied in cosmetology, medicine and food industry. Method lies in interaction of α-tocoferol acetate with alkali, ethylene oxide or propylene oxide at temperature 100-175°C and pressure 1-5 atm. Process is carried out in two stages. At the first stage interaction of α-tocoferol with alkali and ethylene oxide or propylene oxide is performed. Oxide is used in amount 2-10 moles per a mole of α-tocoferol acetate. Obtained product is separated. At the second stage selected intermediate product is oxyakylated with ethylene and/or propylene oxide on presence of alkali.

EFFECT: invention makes it possible to obtain water-soluble polyalkyleneglycol esters of α-tocoferol, which do not contain inorganic admixtures.

2 cl, 2 tbl, 12 ex

FIELD: chemistry.

SUBSTANCE: invention relates to method of obtaining polyalkyleneglycol esters of α-tocoferol, applied in cosmetology, medicine and food industry. Method lies in interaction of α-tocoferol acetate with alkali, ethylene oxide or propylene oxide at temperature 100-175°C and pressure 1-5 atm. Process is carried out in two stages. At the first stage interaction of α-tocoferol with alkali and ethylene oxide or propylene oxide is performed. Oxide is used in amount 2-10 moles per a mole of α-tocoferol acetate. Obtained product is separated. At the second stage selected intermediate product is oxyakylated with ethylene and/or propylene oxide on presence of alkali.

EFFECT: invention makes it possible to obtain water-soluble polyalkyleneglycol esters of α-tocoferol, which do not contain inorganic admixtures.

2 cl, 2 tbl, 12 ex

FIELD: chemistry.

SUBSTANCE: invention relates to method of obtaining polyalkyleneglycol esters of α-tocoferol, applied in cosmetology, medicine and food industry. Method lies in interaction of α-tocoferol acetate with alkali, ethylene oxide or propylene oxide at temperature 100-175°C and pressure 1-5 atm. Process is carried out in two stages. At the first stage interaction of α-tocoferol with alkali and ethylene oxide or propylene oxide is performed. Oxide is used in amount 2-10 moles per a mole of α-tocoferol acetate. Obtained product is separated. At the second stage selected intermediate product is oxyakylated with ethylene and/or propylene oxide on presence of alkali.

EFFECT: invention makes it possible to obtain water-soluble polyalkyleneglycol esters of α-tocoferol, which do not contain inorganic admixtures.

2 cl, 2 tbl, 12 ex

FIELD: chemistry.

SUBSTANCE: invention relates to biologically active compounds, specifically to a group of 2-substituted 1,2,4,5-tetrahydro-3H-pyrrolo[1,2-a][1,4]diazepin-3-ones of general formula where R denotes hydrogen, a straight or branched (C1-C4)-alkyl; a hydroxyalkyl having an alkyl chain with 2-3 C atoms; a phenylalkyl having an alkyl chain with 1-2 C atoms, wherein the phenyl ring can have one or two methoxy groups. The invention also relates to a method of producing said compounds.

EFFECT: novel compounds can be used in medicine as antidepressant and antianxiety agents.

6 cl, 3 tbl, 9 ex

FIELD: chemistry.

SUBSTANCE: compound is a pyrrolidine derivative having a fragment of a sterically hindered phenol, having general formula: where R1 denotes H, Me, Et; R2 denotes Me, Et, i-Pr, i-Bu; Ar denotes Ph, 2-HalPh, 3-HalPh, 4-HalPh, (where Hal denotes F, Cl, Br, I), 2,6-diMePh, 2,3,5,6-tetraFPh, 2-MeOPh, 3-MeOPh, 4-MeOPh, (naphthalen-1-yl), (naphthalen-2-yl), 2-NO2PH, 3-NO2Ph, 4-NO2Ph. The compounds are obtained by mixing a solution of azomethine of formula: where values of R1, R2 are given above, with N-substituted malemide in air and reaction thereof is induced by catalytic amounts of N-tert-butoxycarbonyl derivatives of alpha-amino acids (glycine, alanine, phenylalanine), followed by concentration of the organic phase at low pressure, and cleaning the residue by chromatography on silica gel using CHCl3/MeOH as the eluent.

EFFECT: prolonged antioxidant activity.

2 cl, 2 tbl, 9 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula (IX) wherein radicals and symbols have values given in the claim, and pharmaceutically acceptable salts or tautomers thereof. Said compounds are inhibitors of poly(ADP-ribose)polymerase (PARP) and can be used to treat cancer, inflammatory diseases, reperfusion injuries, ischaemic conditions, stroke, renal failure, cardiovascular diseases, vascular diseases other than cardiovascular diseases, diabetes mellitus, neurodegenerative diseases, retroviral infections, retinal damage, skin senescence and UV-induced skin damage, and as chemo- or radiosensitisers for cancer treatment. The invention also relates to a pharmaceutical composition containing said compounds, use of said compounds and a method of treating said diseases.

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10 cl, 18 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to 3-aroyl-2-arylhydrazonopyrrolo[1,2-a]quinozaline-1,4(2H,5H)-diones of formula:

Ar=Ph, R=Me, R1=H (a); Ar=4-MeC6H4 R=Me, R1=H (b); Ar=Ph, R=H, R1=COOH (c).

EFFECT: there are produced new compounds possessing analgesic activity that makes them being suggested to be used in medicine as drugs with the analgesic properties.

1 cl, 3 tbl, 4 ex

FIELD: chemistry.

SUBSTANCE: invention describes novel, highly crystalline mono(benzenesulphonic acid)besylate salts and polymorphs of the compound of formula (I): , a pharmaceutical composition containing said compounds, methods of producing the salts and use thereof as medicinal agents, particularly for sedative or hypnotic, anxiolytic, muscle relaxation or anticonvulsant purposes.

EFFECT: improved method.

32 cl, 36 dwg, 22 tbl, 10 cl

FIELD: chemistry.

SUBSTANCE: invention relates to a novel tricyclic derivative of chemical formula 1 or pharmaceutically acceptable salts thereof: formula 1, where Y1, Y2 and Y3 independently denote H, C1-C10 alkyl with a straight or branched chain, hydroxy, C1-C10 alkoxy, -CCOR1, -NR2R3 or -A-B; A denotes -O-, -CH2-, -CH(CH3)-, -CH-N- or -CONH-; B denotes -(CH2)n1-Z, -(CH2)n2-NR2R3 or -(CH2)n3-OR1; Z denotes C5-C20 aryl, unsubstituted or substituted with R5 and selectively R6, C3-C10 cycloalkyl, unsubstituted or substituted with R5 and selectively R6, C1-C20 heterocyclic compound, unsubstituted or substituted with R5 and selectively R6; R1 denotes H or C1-C10 alkyl with a straight or branched chain; R2 and R3 independently denote H, C1-C10 alkyl with a straight or branched chain or -(CH2)n4R7; R5 denotes H, C1-C10 alkyl with a straight or branched chain, C5-C20 aryl or C1-C20 heterocyclic compound; R6 denotes H or C1-C10 alkyl with a straight or branched chain; R7 denotes -NR8R9, -COOR1, -OR1, -CF3, -CN, halogen or Z; R8 and R9 independently denote H or C1-C10 alkyl with a straight or branched chain; n1-n4 respectively denote an integer from 0 to 15; Y denotes H or C1-C10 alkyl with a straight or branched chain. The invention also relates to methods of producing a compound of formula 1, compositions containing the described compound and with effective inhibiting activity on poly(ADP-ribose)polymerase (PARP).

EFFECT: obtaining and describing novel compounds which can be suitable for preventing or treating diseases caused by excess PARP activity, especially neuropathic pain, neurodegenerative diseases, cardiovascular diseases, diabetic neuropathy, inflammatory diseases, osteoporosis and cancer.

23 cl, 123 ex, 7 tbl, 2 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a compound of formula possessing action on a BH4 sensitive condition.

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12 cl, 31 dwg, 20 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: described are novel derivatives of hexahydro pyrazino [2,1-c][1,2,4]triazine of general formula (III) (values of radicals are given in invention formula), their pharmaceutically acceptable salts and application of said compounds for obtaining medication for treatment and prevention of acute myeloid leukemia.

EFFECT: obtaining medication for treatment and prevention of acute myeloid leukemia

3 cl, 3 ex, 6 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to substituted tetrahydropyrrolopyrazines of general formula I, wherein R1, R2 and R3 in each case independently mean hydrogen or groups R1 and R2 or R2 and R3 form a common cycle ; R4 and R5 in each case independently mean H; R6 means branched or unbranched saturated, unsubstituted C1-6-alkyl, or unsubstituted heteroaryl wherein heteroaryl is a 5- or 6-member aromatic residue containing 1 heteroatom specified in a group consisting of N, O and S, or means phenyl wherein phenyl is unsubstituted or single-substituted or double-substituted by 1 or 2 substitutes which in each case are independently specified in a group consisting of F, Cl, Br, I, CF3, C1-6-alkyl, O-C1-6-alkyl, and , or means unsubstituted phenyl attached through C1-3-alkyl chain; R4a, R5a and R6a in each case independently mean H; R7 means (CH2)tC(=O)R8, wherein t is equal to 1, (C=O)(CH2)mNR11R12, wherein m is equal to 1 or 2, C(=O)(CH2)n(C=O)R8, wherein n is equal to 1, 2 or 3, (CH2)sNHC(=O)R8, wherein s is equal to 1 or 2; R8 means NR9R10 or saturated, branched or unbranched, unsubstituted C1-6-alkyl; wherein R9 and R10 in each case independently mean H, saturated, branched or unbranched, unsubstituted C1-6-alkyl, or unsubstituted or saturated C3-8-cycloalkyl, or phenyl, or phenyl attached through C1-3-alkyl wherein the alkyl chain is saturated, branched or unbranched, and wherein phenyl in each case is unsaturated or single or double saturated by 1 or 2 substitutes which independently specified in a group consisting of F, Cl, Br, I, CF3, C1-6-alkyl, O-C1-6-alkyl, pyridyl, and , or unsubstituted heteroaryl attached through C1-3-alkyl wherein heteroaryl is a 5-member aromatic residue 1 heteroatom of which are specified in a group consisting of O and S, wherein the alkyl chain is saturated, branched or unbranched, or heterocyclyl, or heterocyclyl attached through C1-3-alkyl wherein the alkyl chain is saturated, branched or unbranched, and wherein heterocyclyl in each case is saturated, unsubstituted or single substituted by benzyl, and heterocyclyl contains cycloalkyl containing 5 to 6 atoms in a cycle wherein 1 or 2 carbon atoms are substituted by 1 or 2 heteroatoms which are specified in a group consisting of N; or both groups R9 and R10 mean (CH2)3-6, CH2CH2OCH2CH2 or CH2CH2NR14CH2CH2; wherein R14 means phenyl or phenyl attached through C1-3-alkyl wherein phenyl in each case is unsaturated or single substituted by a substitute whih is specified in a group consisting of F, Cl, Br, I, O-C1-6-alkyl, and , or R14 means C(=O)R13; wherein R13 means saturated and unbranched C1-6-alkyl or means phenyl condensed with heteroaryl wherein heteroaryl is a 6-member aromatic residue 1 heteroatom of which is specified in a group consisting of N; R11 and R12 in each case independently mean H, saturated, branched or unbranched C1-6-alkyl, or unsubstituted, saturated C3-8-cycloalkyl, C(=O)R20 or S(=O)2R13; wherein R20 means NR21NR22, or R20 means saturated, branched or unbranched C1-6-alkyl, or means saturated C3-8-cycloalkyl, unsubstituted or single substituted by phenyl, or means unsaturated heteroaryl wherein heteroaryl is a 5-member aromatic residue 1 heteroatom of which is specified in a group consisting of O, or means phenyl wherein phenyl is unsubstituted or single substituted by C1-6-alkyl or means phenyl attached through C1-6-alkyl which is unsubstituted or single substituted by a substitute specified in a group consisting of F, Cl, Br, I and CF3, wherein the alkyl chain is saturated or unsaturated, branched or unbranched; wherein R21 and R22 in each case independently mean H or saturated, branched or unbranched, unsubstituted C1-6-alkyl; in the form of bases and salts of physiologically acceptable acids. The invention also refers to methods for preparing them, to drug preparations for treating disorders or diseases related with at least partially KCNQ2/3 K+ canals containing such compounds.

EFFECT: there are prepared new compounds and based drug preparations which can find application in medicine for managing pain, epilepsy, migraine, panic conditions and urinary incontinence.

17 cl, 2 tbl, 91 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to fluorinated compounds of formula , where: D, G and L are independently selected from a group consisting of: CH, C and N, and J and M are independently selected from a group consisting of C and N, under the condition that one of J and M denotes C and the other denotes N, wherein at least two of D, G, M, J and L denote N; X denotes CH2; Y is absent; Z denotes NR1R2; R1 and R2 are independently selected from a group consisting of: hydrogen, C1-C10 alkyl, aryl and heteroaryl, which is associated with aromatic radicals having 6 ring atoms, where 1-2 of these ring atoms are N; each of which can be substituted with one or more halogen atoms; or R1 and R2, together with nitrogen to which they are bonded, form a heterocyclic ring having 5 ring members; R3 is selected from a group consisting of: halogen, C1-C10 alkyl; E denotes aryl which can be substituted with one or more fluoro-substitutes or one or more of the following substitutes: C1-C6 alkyl, QC1-C10 alkyl, QC2-C10 alkenyl, each of which can be substituted with one or more fluoro-substitutes, and where Q denotes O; m denotes a number from 1 to 2; under the condition that: R3 is a fluoro-substitute, or group E includes a fluoro-substitute, or group Z includes a fluoro-substitute, with the condition that E does not denote 4-fluorophenyl or a compound of formula , where D, G and L are independently selected from a group consisting of: CH, C and N, and J and M are independently selected from a group consisting of C and N, under the condition that one of J and M denotes C and the other denotes N, wherein at least two of D, G, M, J and L denote N; X denotes CH2; Y is absent; Z denotes NR1R2; R1 and R2 are independently selected from a group consisting of: hydrogen, C1-C10 alkyl, aryl and heteroaryl, which is associated with aromatic radicals having 6 ring atoms, where 1-2 of these ring atoms are N; each of which can be substituted with one or more of the following substitutes: chlorine, bromine, iodine; or R1 and R2, together with nitrogen to which they are bonded, form a heterocyclic ring having 5 ring members; R3 is selected from a group consisting of: chlorine, bromine, iodine, C1-C10 alkyl; E denotes aryl which can be substituted with one or more chlorine, bromine or iodine atoms, and/or one or more of the following substitutes: C1-C6 alkyl, QC1-C10 alkyl, QC2-C10 alkenyl, each of which can be substituted with one or more substitutes selected from chlorine, bromine, iodine or hydroxy, where Q denotes O, wherein when E denotes phenyl, E does not contain, as a substitute, iodine which is directly bonded to it at position 4; m denotes a number from 1 to 2; wherein at least one of Z, E and R3 includes iodine; under the condition that E does not denote 4-iodophenyl and under the condition that said compound is not a compound of formula (Ia), defined in the following table:

The invention also relates to a pharmaceutical composition based on the compound of formula (I) or (Ia), a diagnosis method, a method of treating said disorders, based on use of the compound of formula (I) or (Ia), and use of the compound of formula (I) or (Ia).

EFFECT: obtaining novel compounds useful in treating disorders in mammals, characterised by anomalous density of peripheral benzodiazepine receptors.

24 cl, 13 dwg, 9 tbl, 23 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention concerns biochemistry and medicine. There is characterised an agent for inactivation of viruses representing derivatives of lysine, glutamic and 6-aminohexanoic acids.

EFFECT: presented agents exhibits ribonuclease, membranolytic and antiviral activities and can be used in medicine as active components for the development of dosage forms used for treating viral diseases.

6 dwg, 4 tbl, 7 ex

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