Derivatives of peptides, the method of production thereof, pharmaceutical composition, inhibiting the human leukocyte elastase
(57) Abstract:Usage: in pharmacology and medicine as inhibitors of elastase of human leukocytes. The essence of the invention: derivatives of peptides f-crystals I. Receiving lead by oxidation of the derived peptide f-crystals II, followed, if necessary, sulfonamideubul compounds, where R3- carboxy or ester group, converting the ester group of carboxylic acid to the corresponding carboxypropyl by hydrolysis. The pharmaceutical composition inhibiting the human leukocyte elastase, containing as active principle derived peptide I in the amount of 100 μg to 250 mg per dosage unit and a pharmaceutically acceptable carrier. The structure of the compounds of formulas I and II are indicated in the text description. 3 S. p. f-crystals, 2 tab. Derivatives of the peptides of General formula
< / BR>where R1is lower alkyl;
R2- lower alkyl, C6H5CH2OCONH(CH2)2C6H5SO2NH(CH2)4C6H5- X - R3- A - or R3AN(R6) CH (R5)CO, where A is OCO, CO, SO2, NHCO;
R3- C6H4(CH2)nwhere n= 0, 1, 2, 4, 2-NH2-5-Cl-phenyl, -C6H4OH, -C
< / BR>where R1is lower alkyl;
R2- lower alkyl, C6H5CH2OCO NH(CH2)2C6H5SO2NH(CH2)4C6H5-; X = R3- A - or R3AN(R6)CH(R5) CO -, where A - OCO -, CO, SO2, NHCO;
R3- C6H4(CH2)n, where n= 0, 1, 2, 4; 2-NH2-5-Cl-phenyl-, -C6H4OH, -C6H4COOH, 4-F-phenyl, 2, 4-di-Cl-phenyl, C1- C2-alkyl, OCOC6H4H3COOC-C6H4CH2-, HOOC - C6H4(CH2)m, where m = 1, 2, 4-CH3OC6H4-, 4-HOOC-C6H4-CH = CH -, 4-C2H5OOC-C6H4CH = CH -, 4-C2H5OOC-C6H4-OCH2- C2H5OOCC6H4(CH2)2,
4-(H2NCOCH2) - C6H4O (CH2)3-, HOOC (CH2)2-, H3COOC(CH2)2- C1- C4-alkyl, CH3O(CH2)2O(CH2)2-, Z-isomer H2NCONHCOCH = CH-, 1-C2H5OOC-cyclopentyl -, 1-HOOC-cyclopentyl, H3C-O-(CH2)2O(CH2)2-, 1-substituted-, 2-(1-substituted)-ethyl-, 1-naphthyl-, (1-naphthyl-SO23SO2NHCO)phenyl, 2-(morpholinoethyl)-, 2-(2-pyridyl)-ethyl-, 2-(thienyl)-C1- C2-alkyl, T-SO2NHCO(CH2)2, where T is lower alkyl, phenyl, 1-substituted, 4-WC6H4SO2NHCOC6H4-, W is hydrogen, NO2, Br, Cl; 4-(4-Cl-C6H4SO2NHCO)C6H4(CH2)2-, 4-(4-Cl-C6H4SO2NHCO)C6H4CH = CH-, 4-(4-Br-C6H4SO2NH)CH2C6H4COC 6H4-;
R4= R6is hydrogen;
R5- butyl, C6H5CH2OCONH(CH2)4- C6H5CH2OCO(CH2)2-,
characterized in that a derivative of the peptide of General formula
< / BR>where the radicals have the above values,
subjected to oxidation, followed, if necessary, sulfonamideubul compounds, where R3- carboxypropyl, or ester group, or conversion of the ester group of carboxylic acid to the corresponding carboxypropyl by hydrolysis.3. The pharmaceutical composition inhibiting the human leukocyte elastase, containing the active principle and a pharmaceutically acceptable carrier, characterized in that, as sports is B> - lower alkyl, C6H5-CH2OCONH(CH2)2C6H5SO2NH(CH2)4- C6H5-,
X = R3- A - or R3AN(R6)CH(R5)CO, where A is OCO, CO, SO2, NHCO;
R3- C6H4(CH2)nwhere n= 0, 1, 2, 4, 2- NH2- 5 - Cl-phenyl, -C6H4OH, -C6H4COOH, 4-F-phenyl, 2, 4-di-Cl-phenyl, C1- C2-alkyl-OCOC6H4-, H3COOC - C6H4CH2-, HOOC - C6H4(CH2)m- where m = 1, 2, 4-CH3OC6H4-, 4-HOOC-C6H4CH = CH -, 4-C2H5OOC - C6H4CH = CH-, 4-C2H5OOC - C6H4OCH2- C2H5OOCC6H4(CH2)2-, -(H2NCOCH2)C6H4O(CH2)3-, HOOC(CH2)2-, H3COOC - (CH2)2- C1- C4-alkyl, CH3O(CH2)2O(CH2)2-, Z-isomer H2NCONHCOCN = CH -, 1-C2H5OOC-cyclopentyl-,
1-HOOC-cyclopentyl-, H3C-O- (CH2)2O(CH2)2-, 1-substituted-, 2-(1-substituted)-ethyl-, 1-naphthyl, (1-naphthyl-SO2NHCO)-C6H4-, (1-naphthyl-SO2NHCO)CH2CH2-, 4-ndimethylacetamide-C6H4(OCH2)k-, k= 0, 1, 2-(2-oxopyrrolidin)-ethyl, 4-(C2)2, where T is lower alkyl, phenyl, 1-substituted, 4-W-C6H4- SO2NHCOC6H4-, W is hydrogen, NO2, Br, Cl, 4-(4-Cl-C6H4SO2NHCO)C6H4(CH2)2-, 4-(4-Cl - C6H4SO2NCO)C6H4CH = CH -, 4-(4Br-C6H4SO2NH)CH2C6H4COC6H4;
R4= R6is hydrogen;
R5-butyl, C6H5CH2OCONH(CH2)4- C6H5CH2OCO(CH2)2-,
in the amount of 100 μg to 250 mg per dosage unit.
FIELD: organic chemistry, medicine.
SUBSTANCE: invention relates to applying compounds of the formula (I) for preparing an antibacterial composition and veterinary composition eliciting with the enhanced activity.
EFFECT: valuable properties of agents.
4 cl, 3 tbl, 78 ex
FIELD: organic chemistry, biochemistry, medicine, pharmacy.
SUBSTANCE: invention relates to macrocyclic peptides of the general formula (I): wherein W means nitrogen atom (N); R21 means hydrogen atom (H), (C1-C6)-alkoxy-, hydroxy-group or N-(C1-C6-alkyl)2; R22 means hydrogen atom (H), (C1-C6)-alkyl, CF3, (C1-C6)-alkoxy-group, (C2-C7)-alkoxyalkyl, C6-aryl or Het wherein het means five- or six-membered saturated or unsaturated heterocycle comprising two heteroatoms taken among nitrogen, oxygen or sulfur atom and wherein indicated Het is substituted with radical R24 wherein R23 means hydrogen atom (H), -NH-C(O)-R26, OR26, -NHC(O)-NH-R26, -NHC(O)-OR26 wherein R26 means hydrogen atom, (C1-C6)-alkyl; R3 means hydroxy-group or group of the formula -NH-R31 wherein R31 means -C(O)-R32, -C(O)-NHR32 or -C(O)-OR32 wherein R32 means (C1-C6)-alkyl or (C3-C6)-cycloalkyl; D means a saturated or unsaturated alkylene chain comprising of 5-10 carbon atoms and comprising optionally one-three heteroatoms taken independently of one another among oxygen (O), sulfur (S) atom, or N-R41 wherein R41 means hydrogen atom (H), -C(O)-R42 wherein R42 means (C1-C6)-alkyl, C6-aryl; R4 means hydrogen atom (H) or one-three substitutes at any carbon atom in chain D wherein substitutes are taken independently of one another from group comprising (C1-C6)-alkyl, hydroxyl; A means carboxylic acid or its alkyl esters or their derivatives. Invention relates to pharmaceutical compositions containing indicated compounds and eliciting activity with respect to hepatitis C virus and these peptides inhibit activity of NS3-protease specifically but don't elicit significant inhibitory activity with respect to other serine proteases.
EFFECT: valuable biochemical and medicinal properties of peptides.
106 cl, 9 tbl, 61 ex
FIELD: organic chemistry, medicine, pharmacy.
SUBSTANCE: invention relates to compounds of the formula (I):
wherein r = 1, 2 or 3; s = 0; t = 0; R1 is taken among group including R11-CO and R12-SO2- wherein R11 is taken among group including (C6-C14)-aryl, (C1-C8)-alkyloxy-group wherein all given group are unsubstituted or substituted with a single or some similar or different substitutes R40; R12 means (C6-C14)-aryl wherein indicated group is unsubstituted or substituted with a single or some similar or different substituted R40; R2 means R21(R22)CH-, R23-Het-(CH2)k-, R23(R24)N-(CH2)m-D-(CH2)n- or R25(R26)N-CO-(CH2)p-D-(CH2)q- wherein D means bivalent residue -C(R31)(R32)-, bivalent (C6-C14)-arylene residue or bivalent residue obtained from aromatic group Het comprising 5 or 6 atoms in cycle among them 1 or 2 are similar or different cyclic heteroatoms taken among group including nitrogen and sulfur atoms; numbers k, m, n, p and q = 0, 1, 2; R21 and R22 that are independent of one another can be similar or different and taken among group including hydrogen atom, (C1-C12)-alkyl, (C6-C14)-aryl and so on; R23 means hydrogen atom, R27-SO2- or R28-CO-; R24, R25 and R26 mean hydrogen atom; R27 is taken among group including (C1-C8)-alkyl, (C6-C14)-aryl and so on; R28 is taken among group including R27, (C1-C8)-alkyloxy-group; R31 and R32 mean hydrogen atom; R40 is taken among group including halogen atom, hydroxy-, (C1-C8)-alkyloxy-group, (C1-C8)-alkyl, (C6-C14)-aryl and so on; R91, R92, R93 and R96 means hydrogen atom; R95 means amidino-group; R97 means R99-(C1-C8)-alkyl; R99 is taken among group including hydroxycarbonyl- and (C1-C8)-alkyloxycarbonyl-; Het means saturated, partially unsaturated or aromatic monocyclic structure comprising from 3 to 6 atoms in cycle among them 1 or 2 are similar or different heteroatoms taken among group comprising nitrogen and sulfur atoms; in all its stereoisomeric forms and also their mixtures in any ratios, and its physiologically acceptable salts. Invention proposes a method for preparing compound of the formula (I). Also, invention proposes a pharmaceutical preparation eliciting inhibitory activity with respect to factor VIIA and containing at least one compound of the formula (I) and/or its physiologically acceptable salts and pharmaceutically acceptable carrier. Invention provides preparing compounds of the formula (I) eliciting power anti-thrombosis effect and useful for treatment and prophylaxis of thrombosis-embolic diseases.
EFFECT: valuable medicinal properties of compounds and composition.
10 cl, 70 ex
FIELD: organic chemistry and drugs.
SUBSTANCE: New class of compounds of general formula 1, where R has formula 2 or 3; other residues are as described in claim of invention is disclosed. Said compounds are interleikyn-1β converting enzyme (ICE) inhibitors and have specific structural and physicochemical properties. Invention also relates to pharmaceutical composition containing said compounds. Compounds and composition of present invention are particularly useful in ICE activity inhibition and thereby can be used as drug for treating of diseases mediated by IL-1, apoptosis, IGIF and IFN-γ, as well as inflammations, autoimmune diseases, bone-destructive disorder, infections, disorder associated with cell proliferation, degenerative and necrotic disorders. Uses of claimed compounds and compositions as well as methods for production of N-acylamino compounds also are disclosed.
EFFECT: effective interleikyn-1beta converting enzyme inhibitors.
64 cl, 35 ex, 35 tbl, 21 dwg
FIELD: medicine, gastroenterology.
SUBSTANCE: traditional eradication therapy should be supplemented with licopid at the dosage of 10 mg per os once daily before breakfast for 10 d. The present innovation prevents transfer of microorganisms into inactive form, accelerates restoration of mucosal epithelial layer in gastroduodenal area, provides complete eradication of microorganisms, that in its turn, favors to prevent disease exacerbation and restoration of gastroduodenal functions.
EFFECT: higher efficiency of therapy.
3 dwg, 2 ex
FIELD: biotechnology, biochemistry.
SUBSTANCE: invention relates to producing the biologically active complex eliciting antioxidant and immunomodulating activity and used in medicine, cosmetics, veterinary science and food industry. The biologically active complex preparing by enzymatic hydrolysis of muscle tissue represents complex of biologically active compounds involving carnosine and anserine in the amount 85-97 wt.-% of the native content of these components in poultry muscle tissue, 1-7 weight parts of amino acids, 0.5-12 weight parts of oligopeptides of molecular mass 10 kDa, not above, and 0.1-15 weight parts of cyclic and polycyclic phenolic compounds as measured for 1 weight part of carnosine and anserine in the complex. This complex is prepared by enzymatic hydrolysis of milled and homogenized water muscle tissue in preferable dilution homogenate with water in the range 0.2-0.6 and with using proteolytic enzymes in the amount 2-5 wt.-% of the protein content and working at pH 4.5-8.5 and at enhanced temperature being preferably at 45-65°C. Product is isolated as extract or powder prepared in drying the extract. Invention provides enhancing effectiveness of the claimed complex.
EFFECT: improved method for preparing, valuable properties of complex.
7 cl, 6 tbl, 6 ex