Obtaining derivative of 1-amino-3-hydroxycyclobutane-1-carboxylic acid
SUBSTANCE: invention relates to method of producing compounds with IVa formula which can be used as precursors for producing amino acids marked with radioisotopes for use in positron emission tomography. According to disclosed method compound of IVa formula is obtained in amount of 100 g or more from the compound of IIIa formula where pH of reaction medium containing compound of IIIa formula is brought to 2.0-5.0 and hydrogenolysis of X group is performed using wet catalyst selected from platinum group metals. R in IVa and IIIa formulae denotes alkyl group with 1-5 carbon atoms, Y denotes protective group of amine and X denotes protective group of alcohol.
EFFECT: method enables safe bring of reaction to completion when implemented in large-scale.
10 cl, 1 tbl, 1 ex
SUBSTANCE: invention relates to method of obtaining methyl ether of (3aR, 4S, 7aR)-4-hydroxy-4-m-tolylethynyloctahydroindole-1-carboxylic acid of formula (I), with application of novel intermediate compounds of formulas (II) and (III).
EFFECT: improvement of method.
10 cl, 30 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: declared invention refers to chemical-pharmaceutical industry, and concerns 2,2,2-Trifluoro-1-trifluoromethylethyl ester of cyclohexylcarbamine acid which is prepared starting with cyclohexylisocyanate and 1-hydrohexafluorisopropanole at 20°C in benzene in the presence of catalytic amounts of triethylamine.
EFFECT: compound (I) is an effective and selective irreversible carboxylesterase inhibitor with low acute toxicity in warm-blooded, and may be used in preclinical studies on rodents for decreasing carboxylesterase hydrolysis rate of the drugs containing ester and/or amide groups, and also as insect carboxylesterase inhibitors in pharmaceutical composition and pesticide formulations for increasing their efficacy.
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention relates to amide of δ-amino-γ-hydroxy-ω-arylalcane acid of formula and its pharmaceutically acceptable salts. Also described are pharmaceutical compositions, which include said compounds, and application of said compounds for preparation of medication, intended for treatment of pathological states, associated with renin activity, in particular for treatment of hypertension.
EFFECT: obtaining pharmaceutically acceptable salts, which possess rennin-inhibiting ability.
21 cl, 161 ex
SUBSTANCE: described are compounds of formula I in form of free base or acid-additive salt, method of their obtaining, pharmaceutical composition based on them and their application s antagonists of metabotropic glutamate receptors (mGluR5). The invention can be applied in the treatment of the illnesses connected with the disorder of glutamatic signal transfer and the disorder of nervous system partially or completety mediate mGluR5. In general formula T represents 0 or 1, A represents hydroxy, X represents hydrogen, Y represents hydrogen or A forms simple bond with X or Y; ring methylene group directly bound with CH(X)-, can be dimethylated; R0 represents hydrogen, C1-C4alkyl, C1-C4alkoxy, halogen, cyano, and R represents -COR3, -COOR3 or -SO2R6,where R3 represents C1-C4alkyl, C3-C7cycloakyl, and R6 represents C1-C4alkyl, C3-C7cycloakyl, or R represents -C(O)R3, where R3 represents furanyl, trifluoromethyl, pyridinyl, morpholinyl or methylpiperasinyl; or -C(O)OR3, where R3 represents tetrahydrofuranyl, R' represents hydrogen, C1-C4alkyl or 4-methoxybenzyl, and R" represents hydrogen or C1-C4alkyl, or R' and R" together form group -CH2-(CH2)p-, where p represents 0, 1 or 2, one of symbols n and p does not represent 0, on condition that R0 does not represent hydrogen, trifluoromethyl and methoxy, when m represents 1, n represents 0, A represents hydroxy, X and Y both represent hydrogen, R represents COOEt and R' and R" together form group -(CH2)2-.
EFFECT: efficient application of compounds for treatment of diseases caused by disturbance of transduction of glutamatergic signal and diseases of nervous system.
8 cl, 11 ex
FIELD: organic synthesis.
SUBSTANCE: invention provides compounds of general formula I:
, where R1 represents -CO-Ra, -SO2-Rb, or aryl optionally substituted by lower alkoxy, wherein Ra represents cycloalkyl, cycloalkyl(lower)alkyl, cycloalkyloxy, aryl, aryloxy, aryl(lower)alkyl, aryl(lower)alkoxy, aryloxy(lower)alkyl, aryl-S-(lower)alkyl, aryl(lower)alkenyl, provided that aryl group can be optionally substituted by halogen, lower alkyl, hydroxy, nitro, cyano, lower alkoxy, phenyl, CF3, cyano(lower)alkyl, lower alkyl-C(O)NH, lower alkyl-CO, and lower alkyl-S; heteroaryl, heteroaryl(lower)alkyl, or heteroaryl(lower)alkoxy, provided that heteroaryl group is 5- or 6-membered ring or bicyclic aromatic group constituted by two 5- or 6-membered rings including 1-3 heteroatoms selected from oxygen, nitrogen, and sulfur and that heteroaryl group can be optionally substituted by lower alkoxy; Rb represents aryl, aryl(lower)alkyl, or heteroaryl, aryl group optionally substituted by halogen, cyano, or lower alkyl-C(O)NH; R2 and R3 represent hydrogen atoms; R4 representshydrogen or lower alkyl; R5 represents hydrogen, lower alkyl, cycloalkyl, benzodioxyl, or aryl optionally substituted by lower alkyl, halogen, lower alkoxy, hydroxy, or (lower)alkyl-C(O)O; n is 1 or 2; and pharmaceutically acceptable salts thereof and/or pharmaceutically acceptable esters thereof. Invention also provides a pharmaceutical composition exhibiting inhibitory activity with regard to cysteine proteases of the cathepsin family, which composition comprises compound of formula I, pharmaceutically acceptable recipient, and/or adjuvant.
EFFECT: increased choice of cysteine protease inhibitors.
34 cl, 1 tbl, 13 ex
SUBSTANCE: invention relates to method of enantioselective allylic amination of derivatives of α,β-unsaturated carboxylic acids with obtaining enantiomerically enriched derivatives, described by formulae II , III , VII and VIII . Method is performed by interaction of racemic mixture of carboxylic acid derivative with chiral ligand on catalyst [Pd(allyl)Cl]2 in presence of nucleophilic reagent, selected from potassium phthalimide or amine of formula R1R2NH, where R1 represents benzyl, n-butyl or cyclohexyl group, R2 represents hydrogen or benzyl group.
EFFECT: enantioselective palladium-catalysed ally lamination of derivatives of α,β-unsaturated carboxylic acids with obtaining products with increased enantionmeric excess.
10 cl, 6 dwg, 3 tbl, 48 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to chemistry and pharmaceutics, namely an improved method for preparing iodide or methylsulphate neostigmine which can find application as drugs. The method involves preparing sodium 3-dimethylaminophenolate, enabling its reaction with dimethylcarbamoyl acid chloride and reaction of prepared 3-((dimethylcarbomoyloxy)phenyl)-dimethylamine with an alkylating agent (iodomethane or dimethylsulphate). The method is characterised by the fact that target compounds are prepared by the reaction of 3-dimethylaminophenol with 2.0-2.5 molar excess of sodium metal in the toluene medium in boiling, addition of 1.5 molar excess of dimethylcarbamoyl acid chloride, washing out of the toluene filtrate with a sodium alkali solution and water, evaporation of a solvent and keeping of 3-((dimethylcarbomoyloxy)phenyl)-dimethylamine with the relevant alkylating agent for 24 hours in the absolute diethyl ester medium.
EFFECT: method enhancing the 3-dimethylaminophenol conversion, as well as providing higher yield and purity of the end product.
SUBSTANCE: invention relates to a method for synthesis of ethylenediamine derivatives (4), having a halogenated carbamate group and an acyl group, involving catalytic hydrogenation of aminonitrile with a halogen-substituted carbamate group in the presence of an acid and then acylation of the formed amino derivative. The initial aminonitrile may be obtained with high output by reacting an amino acid amide with a halogen-substituted carbamating agent in the presence of water and then reacting the formed amide, which has a halogen-substituted carbamate group, with a reducing agent such as a Wilsmeyer reagent.
EFFECT: high yield.
22 cl, 45 ex
SUBSTANCE: invention refers to novel compounds of the general formula (I) , where R1, R2 are independently H or C1-C6-alkyl; R3, R4 are independently H or C1-C6-alkyl; R5 is halogen, CN; n, m or o are 0, 1 or 2; and to pharmaceutically acceptable salts thereof.
EFFECT: compounds with monoaminooxidase B inhibition properties applicable in obtainment of pharmaceutical drugs with relevant effect.
14 cl, 3 dwg, 31 ex
SUBSTANCE: invention relates to compounds of structural formula I and their pharmaceutically acceptable salts. In structural formula I , X is oxygen; Y is oxygen; Y1 Y2, R7 and R4 represent H; X1 and X2 are independently selected from a group consisting of hydrogen, an alkyl group containing 1 to 5 carbon atoms, in which one or more hydrogen atoms of the alkyl group can be substituted with a halogen, aryl group containing 6 to 10 carbon atoms or a cycloalkyl group containing 3 to 9 carbon atoms, or a 5-9-member heterocyclic group with 2 heteroatoms selected from N and O, or a cycloalkyl group containing 5 to 9 carbon atoms; values of the rest of the radicals are given in the formula of invention. The invention also pertains to a pharmaceutical composition having properties of selective inhibitors of type IV phosphodiesterase, containing a therapeutically effective amount of the invented compound.
EFFECT: increased effectiveness of the compounds.
6 cl, 23 ex
SUBSTANCE: disclosed is a method of producing a radioactive, fluorine-labelled organic compound of formula , involving a step of heating a compound of formula at temperature of 40-90°C (where R1 denotes a linear or branched alkyl with 1-10 carbon atoms or an aromatic substitute; R2 denotes a linear or a branched halogen-alkylsuphonic acid substitute with 1-10 carbon atoms, a linear or branched alkylsulphonic acid substitute with 1-10 carbon atoms, a fluorosulphonic acid substitute or an aromatic sulphonic acid substitute, and R3 denotes a protective group) while stirring in an inert organic solvent in the presence of a phase transfer catalyst, 18F ions and calcium ions for radioactive fluorine labelling, and concentration of the phase transfer catalyst in the inert organic solvent is not less than 70 mmol/l.
EFFECT: disclosed method improves output of radioactive fluorination.
5 cl, 43 ex, 5 tbl, 6 dwg
SUBSTANCE: invention relates to a method of producing a radioactive fluorine-labelled organic compound of formula (3). The method involves a step for splitting an ester of formula (1), where R1 is a straight or branched C1-C10 alkyl and R2 is a protecting group selected from straight or branched C2-C7 alkyloxycarbonyl groups, passed through and held in a reverse phase column containing filler with a structure in which C2-C18 alkyl groups are attached to a substrate by silicon. In order to split said ester, alkali solution is fed into the column, after which alkaline solution is discharged from the column to obtain a compound of formula (2), where X is sodium or potassium and R2 is a protecting group selected from straight or branched C2-C7 alkyloxycarbonyl groups. At the next step, the protecting group R2 of the compound of formula (2), obtained at the ester splitting step, is removed to obtain a compound of formula (3).
EFFECT: method enables to reduce the amount of nonradioactive impurities and obtain a compound of formula (3) with good output.
2 cl, 3 dwg, 5 tbl, 2 ex
SUBSTANCE: new pure syn-aminoacids of formulas I and II have ability of specific binding in biological system and may be used to produce image of tumor. II and I. In formulae I and II Y and Z are independently selected from group made of CH2 and (CR4R5)n, n=1, 2; R1-R3 are independently selected from group made of H and alkyl C1-C4; R4, R5 = H and R7 = 18F. Invention is related to method of synthesis of syn-aminoacids with formula II, which includes stages of ketone transformation into trans-spirit of formula I and transformation of produced trans-spirit into syn-aminoacid of formula II, and also to pharmaceutical composition for production of tumor image and method for production of tumor image.
EFFECT: improved efficiency of compounds and method of treatment.
12 cl, 1 tbl, 3 dwg, 3 ex
) is a complex ethyl ester of trans-2-dimethylamino-1-phenyl-3 - cyclohexen - trans-1-carboxylic acid in the form of primary orthophosphate and solid pharmaceutical composition exhibiting analgetic activity" target="_blank">
SUBSTANCE: invention refers to a method for producing a mixture of aspartic acid diethoxysuccinate and an amino acid derivative of general formula , which can find application as a chelating agent. In formula I, n is equal to 1-10, m is equal to 0 or 1, whereas R represents a hydrogen atom or an alkali or alkali earth metal ion. The method involves carrying out a reaction of maleate and diethanolamine in the alkali medium in the presence of a lanthanide catalyst element to form aspartic acid diethoxysuccinate. That is followed by adding aspartic acid, which reacts with unreacted maleate to form iminodisuccinic acid, i.e. an amino acid derivative of formula I, wherein m is equal to 0, or adding a diamine derivative of general formula NH2(CH2)nNH2 II, wherein n is such as described above, which reacts to unreacted maleate to form the amino acid derivative of formula I, wherein m is equal to 1, whereas n is such as specified above.
EFFECT: method enables producing the mixtures of chelating agents with the use of unreacted maleate from the process of producing aspartic acid diethoxysuccinate that makes the presented method more cost-efficient.
11 cl, 2 tbl, 2 ex