Derivatives of 1,3-propane diol and their use as biologically active substances
The invention relates to new compounds with the structure associated 1,3-propane diol, having the ability to penetrate lipid barriers, formula 1, where R1denotes an acyl group or a group of fatty alcohol, derived from C12-30preferably C16-30the fatty acids preferably with two or more double bonds in the CIS - or TRANS-position, and R2denotes hydrogen, acyl group or the group of fatty alcohol, which is the same or different from that specified for R1or is a biologically active residue that is different from the rest of Niacin, the chemical structure of which allows you to connect with 1,3-propane diol through the available carboxyl, alcohol or amino group. Connection with the structure associated 1,3-propane diol, having the ability to penetrate lipid barriers, formula 1, where R1denotes an acyl group or a group of fatty alcohol, derived from C12-30preferably16-30the fatty acids preferably with two or more double bonds in the CIS - or TRANS-position, and R2denotes hydrogen, acyl group or the group of fatty alcohol, which is the same or different from that specified for R1or alabastine with 1,3-propane diol through the available carboxyl, alcohol or amino group, in which between the group R1and/or R2and the rest of 1,3-propane diol included phosphate, succinate or other bifunctional acid group, in particular, when R2is a biologically active rest with a hydroxyl or amino functional groups. Drug therapy for transfer of a drug or other active substance through the lipid membranes in the body, or having the effect, of additional or complementary, or synergistic with R1containing as active agent a compound of formula 1. The technical result - new compounds with the ability to penetrate lipid barriers. 7 C. and 8 C.p. f-crystals.
Description text in facsimile form (see graphic part).
Claims
1. Connection with the structure associated 1,3-propane diol, having the ability to penetrate lipid barriers:
where R1denotes an acyl group or a group of fatty alcohol, derived from C12-C30preferably16-C30fatty acids regroup or group of fatty alcohol, which is the same or different from that specified for R1or is a biologically active residue that is different from the rest of Niacin, the chemical structure of which allows you to connect with 1,3-propane diol through the available carboxyl, alcohol or amino group.2. Connection with the structure associated 1,3-propane diol, having the ability to penetrate lipid barriers:
where R1denotes an acyl group or a group of fatty alcohol, derived from C12-C30preferably16-C30fatty acids, preferably with two or more double bonds in the CIS - or TRANS-position; R2denotes hydrogen, acyl group or the group of fatty alcohol, which is the same or different from that specified for R1or is a biologically active residue that is different from the rest of Niacin, the chemical structure of which allows you to connect with 1,3-propane diol through the available carboxyl, alcohol or amino group, in which between the group R1and/or R2and the rest of 1,3-propane diol included phosphate, succinate or other bifunctional acid group, in particular, when R2is a biologically active OS the lot is an essential fatty acid of the number of n-6 or n-3, or oleic acid, or columbinus acid, or prinarovie acid, or conjugated linoleic acid.4. Connection on p. 3, in which the fatty acid is gamma-linolenic acid, di-Homo-gamma-linolenic acid, arachidonic acid, atenolol acid, stearidonic acid, eicosapentaenoic acid, docosapentaenoic acid n-3, docosahexaenoic acid or conjugated linoleic acid.5. Connection PP. 1-3 or 4, in which R2a drug or other active substance, for which you want to penetrate the lipid membranes in the body to provide the necessary action within the cell or move to the cell in which it must act, or to pass through the skin, the blood-brain or other barriers.6. Connection PP. 1-3 or 4, in which regardless of the need to penetrate through the lipid membrane R2a drug, vitamin, amino acid, antioxidant or another active substance which is required to provide additive, complementary, or synergistic action with R1.7. Drug therapy for transferring the medicament is optional, or complementary, or synergistic with R1, wherein the active agent comprises a compound according to any one of the preceding paragraphs. 1-4.8. Compounds according to any one of paragraphs. 1-4 as such, except for compounds in which R1and R2represent the remains of saturated fatty acids, and compounds in which R1and R2have the same values and are derived from oleic acid, linoleic acid or alpha-linolenic acid.9. Compounds according to any one of paragraphs. 1-6 to obtain preparations for skin care or hair care or treatment of skin diseases.10. Compounds according to any one of paragraphs. 1-6 to obtain food, food additives or feed additives.11. Derivatives of 1,3-propane diol containing two fatty acids, one of which fatty acid is gamma-linolenic acid or di-Homo-gamma-linolenic acid, and other gamma-linolenic acid, di-Homo-gamma-linolenic acid, stearidonic acid, eicosapentaenoic acid, docosahexaenoic acid, conjugated linoleic acid or columbinus acid intended for use in therapy.12. Derivatives of 1,3-propane diol containing two fatty ka-linolenic acid, docosahexaenoic acid, di-Homo-gamma-linolenic acid or eicosapentaenoic acid, intended for use in therapy.13. Derivatives of 1,3-propane diol containing two fatty acids, one of which fatty acid is eicosapentaenoic acid, and the other of eicosapentaenoic acid or docosahexaenoic acid, intended for use in therapy.14. Derivatives of 1,3-propane diol, containing in one position fatty acid selected from gamma-linolenic acid, di-Homo-gamma-linolenic acid, arachidonic acid, stearidonic acid, conjugated linoleic acid, eicosapentaenoic acid or docosahexaenoic acid, and in another position of the tool selected from the following chemical structure which allows it to communicate with 1,3-propane diol through the available carboxyl, alcohol or amino group: (a) tryptophan; (b) phenylalanine; (c)arginine; (d) carnitine or a derivative of carnitine; (e) any other amino acid or its derivatives or aminolevulinate acid or its derivatives; (f) adenylosuccinate or its derivatives; (g) aspirin, salicylic acid, indomethacin, ibuprofen, or any non-steroidal anti-inflammatory securitiesin; (i) any anti-malarial or Antiprotozoal agent, in particular chloroquine, mepacrine, chinacan and mefloquine; (j) any antifungal drug, in particular metronidazole and antifungal imidazoles, nitroimidazoles and amphotericin; (k) any anti-inflammatory steroid, in particular hydrocortisone and betamethasone, beclomethasone and budesonide; (l) any gonadally steroid, in particular oestrogen, POCs and androgens; (m) any adrenal steroid, particularly dehydroepiandrosterone; (n) any retinoid, in particular, tretinoin and isotretinoin; (o) any anti-cancer agent; (p) any antipsychotic agent; (q) any antidepressant; (r) any tranquilizer; (s) any immunosuppressive agent, in particular cyclosporine and tacrolimus; (t) any proton pump inhibitor or H2 antagonist; (u) any diuretic; (v) any calcium antagonist; (w) any angiotensin-converting enzyme inhibitor or antagonist of angiotensin; (x) any beta-blocker; (y) any antiepileptic drug, particularly phenytoin, carbamazepine, valproate, ethosuximide, vigabatrin or lamotrigine; (z) any gipolipidemicheskie tool, in particular the fibrates and statins; (AA) any p is the based tool, used in radiology, including connection of diatrizoate, iodipamide, ioglycamide, iopanoic, opendylan, iothalamate, ioxaglate, metrizamide and their derivatives; (dd) any peptide or protein, including insulin, calcitonin or erythropoetin; (EE) any vitamin; (ff) any antioxidant; (gg) any porphyrin, chlorin or drug-based bacteriochlorin, in particular tetrakis(hydroxyproline) derivatives.15. Derivatives of 1,3-propane diol under item 14, containing in one position fatty acid selected from gamma-linolenic acid, di-Homo-gamma-linolenic acid, arachidonic acid, stearidonic acid, conjugated linoleic acid, eicosapentaenoic acid or docosahexaenoic acid, and in another position - vitamin or antioxidant, chemical structure which allows it to communicate with 1,3-propane diol through the available carboxyl, alcohol or amino group, for use in food additives, food or nutrients.Priority points and features: 01.05.1995 on PP. 1 and 2, where R1and R2groups derived from fatty acids with two or more CIS or TRANS double bonds, biologically active balance associated with 1,3-propandiol is Noah linoleic acid;p. 14, where derivatives of 1,3-propane diol, containing in one position fatty acid selected from gamma-linolenic acid, di-Homo-gamma-linolenic acid, arachidonic acid, stearidonic acid, conjugated linoleic acid, eicosapentaenoic acid or docosahexaenoic acid, and in another position the drug (a), (C), amino acids (e), (g), (h), metronidazole (j), (k), (o), (p), (q) and b vitamins (In) (its);
p. 15, where derivatives of 1,3-propane diol, containing in one position fatty acid selected from gamma-linolenic acid, di-Homo-gamma-linolenic acid, arachidonic acid, stearidonic acid, conjugated linoleic acid, eicosapentaenoic acid or docosahexaenoic acid, and in another position of the b vitamin;
21.08.1995 under item 3, except conjugate linoleic acid;
p. 9 - for skin care;
PP. 10, 12 and 13;
15.03.1996 on PP. 1 and 2, except for the sign "is different from the rest of the Niacin";
p. 8, except signs, excluding the number of compounds;
p. 14, where derivatives of 1,3-propane diol, containing in one position fatty acid selected from gamma-linolenic acid, di-Homo-gamma-linolenic acid, arachidonic acid, stearidonic acids is drop - drug (b), derivatives of carnitine (d), chloroquine, mepacrine (i), (v), (cc), peptides (dd), (EE), (ff);
p. 15, except conjugate linoleic acid.
-OR SIG6N(R7)-, where R6- alkyl, R5choose from the group of alkyl, aryl, including heteroaryl, -COR7, -SO2R7and-COR10where R7Is H, alkyl or aryl, including heteroaryl, R2Is F, Cl, Br, J, alkyl, aryl, including heteroaryl, formyl, acyl, C(O)NR7R10or C(O)or SIG7, m = 0, 1, or 2, R3selected from the group comprising R7OR7N(R7)(R10) and CH(R7)C(O)R8, R8is R7OR7and NR7R10, R9is hydrogen, alkyl, aryl, including heteroaryl, -C(O)R10, -SO2R10, -C(S)OTHER10, -C(NH)NH(R10), -C(O)OTHER10, R10- H, alkyl, or aryl, including heteroaryl, and in each case, it is not necessarily different from R7X represents an ion halogen provided that 1) when two alkyl groups are the same carbon or nitrogen, they are not necessarily linked together with the formation of a cyclic structure, and (2) nitrogen heteroaryl ring R1
-OR SIG6N(R7)-, where R6- alkyl, R5choose from the group of alkyl, aryl, including heteroaryl, -COR7, -SO2R7and-COR10where R7Is H, alkyl or aryl, including heteroaryl, R2Is F, Cl, Br, J, alkyl, aryl, including heteroaryl, formyl, acyl, C(O)NR7R10or C(O)or SIG7, m = 0, 1, or 2, R3selected from the group comprising R7OR7N(R7)(R10) and CH(R7)C(O)R8, R8is R7OR7and NR7R10, R9is hydrogen, alkyl, aryl, including heteroaryl, -C(O)R10, -SO2R10, -C(S)OTHER10, -C(NH)NH(R10), -C(O)OTHER10, R10- H, alkyl, or aryl, including heteroaryl, and in each case, it is not necessarily different from R7X represents an ion halogen provided that 1) when two alkyl groups are the same carbon or nitrogen, they are not necessarily linked together with the formation of a cyclic structure, and (2) nitrogen heteroaryl ring R1
-OR SIG6N(R7)-, where R6- alkyl, R5choose from the group of alkyl, aryl, including heteroaryl, -COR7, -SO2R7and-COR10where R7Is H, alkyl or aryl, including heteroaryl, R2Is F, Cl, Br, J, alkyl, aryl, including heteroaryl, formyl, acyl, C(O)NR7R10or C(O)or SIG7, m = 0, 1, or 2, R3selected from the group comprising R7OR7N(R7)(R10) and CH(R7)C(O)R8, R8is R7OR7and NR7R10, R9is hydrogen, alkyl, aryl, including heteroaryl, -C(O)R10, -SO2R10, -C(S)OTHER10, -C(NH)NH(R10), -C(O)OTHER10, R10- H, alkyl, or aryl, including heteroaryl, and in each case, it is not necessarily different from R7X represents an ion halogen provided that 1) when two alkyl groups are the same carbon or nitrogen, they are not necessarily linked together with the formation of a cyclic structure, and (2) nitrogen heteroaryl ring R1
< / BR>in which X denotes O or S;R1and R2which may be identical or different, denote hydrogen, (C1-C6)alkyl or (C3-C8)cycloalkyl or R1and R2together with the carbon atom to which they are attached, form a (C3-C8)cycloalkyl;
R3means (C6-C12)aryl, optionally substituted by one or more radicals Y, which may be the same or different;
Y represents halogen;
R4and R5represent hydrogen;
Ar denotes one of the following groups or WITH:
< / BR>T represents hydrogen or (C1-C6)alkyl;T3and T4which may be identical or different, denote (C1-C6)alkyl, (C1-C6)alkoxy, (C1-C6)allylthiourea;
R6and R7each denotes hydrogen or R6and R7together represent a bond;
Z denotes either (I) the divalent group-CHR9- in which the R11-, in which R10and R11together they form a bond that Z represents the group-CH=CH-, or R10and R11that may be the same or different, have the meanings indicated above for R9or (III) a divalent group-CHR12-CHR13-CH2-, in which R12and R13together they form a bond, Z represents-CH=CH-CH2-, or R12and R13that may be the same or different, have the meanings indicated above for R9,
as well as their additive salts with pharmaceutically acceptable acids or bases, and method of production thereof, pharmaceutical compositions and drug manifesting gipolipedimecescoe and antiatherosclerotic action based on them
FIELD: medicine, endocrinology, pharmacology, pharmacy.
SUBSTANCE: invention relates to a pharmaceutical combined composition used for treatment or prophylaxis of hypertension in patients suffering with diabetes mellitus. The composition comprises AT1-antagonist valsartan or its pharmaceutically acceptable salt and calcium channel blocking agent or its pharmaceutically acceptable salt, and pharmaceutically acceptable carrier. The composition elicits synergistic effect and expanded spectrum effect.
EFFECT: improved and valuable medicinal properties of composition.
10 cl, 3 tbl
FIELD: medicine, toxicology.
SUBSTANCE: invention proposes applying 15% aqueous solution of 1-methyl-5-[2'-(benzyldimethylammonio)ethyl]carbamoyl pyridinium-2-aldoxime dichloride that exceeds the 15% solution of dipiroxime (TMB-4, trimedoxime bromide) used in native medicinal practice by the curative effectiveness. Invention can be used in urgent treatment of acute poisoning with organophosphorus poisonous substances eliciting neuroparalytic effect.
EFFECT: enhanced effectiveness, valuable medicinal properties of agent.
3 tbl
FIELD: organic chemistry, biochemistry, medicine, pharmacy.
SUBSTANCE: invention relates to new sulfur-containing compounds of the formula (I):
their pharmaceutically acceptable salts or solvates, or salt solvates wherein R1 represents (C1-C6)-alkyl, cycloalkyl, aryl, aliphatic or aromatic heterocyclyl substituted with one more basic group, such as amino-, amidino- and/or guanidine-group; R2 represents hydrogen atom (H), alkyl, alkylthio-, alkoxy- or cycloalkyl group; R3 represents COOR5, SO(OR5), SOR5 and others; R4 represents hydrogen atom (H) or (C1-C6)-alkyl; R6 represents hydrogen atom (H); X represents C(Z)2 or NR6CO; Y represents C(Z)2; Z represents hydrogen atom (H), (C1-C6)-alkyl, aryl or cycloalkyl. Indicated compounds inhibit activity of carboxypeptidase U and can be used for prophylaxis and treatment of diseases associated with carboxypeptidase U.
EFFECT: improved preparing method, valuable biochemical and medicinal properties of compounds.
14 cl, 36 ex
FIELD: organic chemistry, biochemistry, medicine, pharmacy.
SUBSTANCE: invention relates to new sulfur-containing compounds of the formula (I):
their pharmaceutically acceptable salts or solvates, or salt solvates wherein R1 represents (C1-C6)-alkyl, cycloalkyl, aryl, aliphatic or aromatic heterocyclyl substituted with one more basic group, such as amino-, amidino- and/or guanidine-group; R2 represents hydrogen atom (H), alkyl, alkylthio-, alkoxy- or cycloalkyl group; R3 represents COOR5, SO(OR5), SOR5 and others; R4 represents hydrogen atom (H) or (C1-C6)-alkyl; R6 represents hydrogen atom (H); X represents C(Z)2 or NR6CO; Y represents C(Z)2; Z represents hydrogen atom (H), (C1-C6)-alkyl, aryl or cycloalkyl. Indicated compounds inhibit activity of carboxypeptidase U and can be used for prophylaxis and treatment of diseases associated with carboxypeptidase U.
EFFECT: improved preparing method, valuable biochemical and medicinal properties of compounds.
14 cl, 36 ex
FIELD: organic chemistry, medicine.
SUBSTANCE: invention describes N-substituted azaheterocyclic carboxylic acids and their esters of the formula (I):
wherein R1 and R2 represent independently hydrogen, halogen atom, NR6R7 or (C1-C6)-alkyl; Y represents >N-CH2 or >C=CH2- wherein only underlined atom is a component of the ring system; X represents -O-, -S-, -CH2CH2- wherein R6 and R7 represent independently (C1-C6)-alkyl; r = 1, 2 or 3; Z represents heterocycle taken among formulas (a), (b), (c), (d), (f), (k), (g) and (j) given in the invention claim. Also, invention relates to a method for their preparing and pharmaceutical composition based on compounds of the formula (I). Invention describes a method for inhibition of neurogenous pain, inflammation and blood glucose level increase to patient by administration to patient the effective dose of compound of the formula (I). Compounds of the formula (I) elicit ability to inhibit the neurogenous pain and blood glucose enhanced level.
EFFECT: improved preparing method, valuable medicinal properties of compounds.
13 cl, 1 tbl, 30 ex
FIELD: chemistry of metalloorganic compounds, medicine, oncology.
SUBSTANCE: invention relates to derivatives of platinum tetrachloride and to a method for their preparing also. Invention proposes compounds of the formula PtCl4 x 2 Li wherein Li represents N-(2-nitroxyethyl)nicotinamide or N-(2-nitroxyethyl)isonicotinamide, or nicotine hydroxamic acid, or isonicotine hydroxamic acid. Also, invention proposes a method for preparing these compounds that involves interaction of pyridine carboxylic acid nitroxyethylamides or hydroxamic acids, or their hydrochlorides with potassium hexachloroplatinate followed by isolation of the end product. Invention provides synthesis of the unknown early chelate platinum compounds that are physiologically active substances and can be used in medicinal practice instead cisplatin as effective anti-metastatic medicinal agents with low toxicity.
EFFECT: improved preparing method, enhanced and valuable medicinal properties of compounds.
2 cl, 3 ex
FIELD: chemistry of metalloorganic compounds, medicine, oncology.
SUBSTANCE: invention relates to derivatives of platinum tetrachloride and to a method for their preparing also. Invention proposes compounds of the formula PtCl4 x 2 Li wherein Li represents N-(2-nitroxyethyl)nicotinamide or N-(2-nitroxyethyl)isonicotinamide, or nicotine hydroxamic acid, or isonicotine hydroxamic acid. Also, invention proposes a method for preparing these compounds that involves interaction of pyridine carboxylic acid nitroxyethylamides or hydroxamic acids, or their hydrochlorides with potassium hexachloroplatinate followed by isolation of the end product. Invention provides synthesis of the unknown early chelate platinum compounds that are physiologically active substances and can be used in medicinal practice instead cisplatin as effective anti-metastatic medicinal agents with low toxicity.
EFFECT: improved preparing method, enhanced and valuable medicinal properties of compounds.
2 cl, 3 ex
FIELD: organic chemistry, biochemistry, medicine, endocrinology.
SUBSTANCE: invention relates to a trans-olefinic activator of glucokinase representing compound taken among the group consisting of olefinic amide of the formula (I): wherein R1 and R2 mean independently of one another hydrogen, halogen atom, nitro-group, perfluoro-(lower)-alkyl, (lower)-alkylsulfonyl or (lower)-alkylsulfonylmethyl; R means -(CH2)m-R3 or lower alkyl comprising from 2 to 4 carbon atoms; R3 means cycloalkyl comprising from 3 to 8 carbon atoms; R4 means the group:
or unsubstituted, or monosubstituted five- or six-membered heteroaromatic ring linked by ring carbon atom with indicated amino-group wherein this five- or six-membered heteroaromatic ring comprises from 1 to 2 heteroatoms taken among the group consisting of sulfur or nitrogen atom wherein one heteroatom being as nitrogen atom is arranged near with binding ring carbon atom, and wherein indicated monosubstituted heteroaromatic ring is substituted at ring carbon atom not adjacent with mentioned binding carbon atom with a substitute taken among the group consisting of halogen atom and group of the formula:
m = 0 or 1; n = 0, 1, 2, 3 or 4; R7 means hydrogen atom or lower alkyl; Δ means trans-configuration relatively to a double bond; or its pharmaceutically acceptable salt. Also, invention relates to pharmaceutical composition, method for prophylactic or therapeutic treatment of diabetes mellitus of type II and to methods for preparing compounds of the formula (I). Invention provides preparing activators of glucokinase that enhance insulin secretion in treatment of diabetes mellitus of type II.
EFFECT: valuable medicinal properties of compounds.
25 cl, 29 ex
