The method of obtaining esters of n-substituted 14 - hydroxymorphinone

 

The invention relates to organic chemistry, specifically to a method for producing esters of N-substituted 14-hydroxymorphinone that are important narcotic analgesic and/or antagonistic means - opiate receptor blockers prolonged action. Describes how to obtain esters of N-substituted 14-hydroxymorphinone General formula where R is allyl, cyclopropylmethyl, R' is chosen from the group consisting of acid residues of saturated or unsaturated carboxylic acids with 3-18 carbon atoms, by reacting the corresponding 14-hydroxymorphinan with allermuir agent selected from the group consisting of anhydrides of saturated or unsaturated carboxylic acids with 3-18 carbon atoms, in the environment of organic solvent in the presence of acceptor galgenwaard - carbonate or bicarbonate of an alkali metal, in this case, the interaction is subjected to 10-35%aqueous solution of N-substituted 14-hydroxymorphinan hydrochloride, the reaction of lead in the environment of water-immiscible chlorinated aliphatic hydrocarbon in the presence of an aqueous solution of acceptor galgenwaard. The technical result - obtaining high yields of final productsimages (see the graphical part).

Claims

1. The method of obtaining esters of N - substituted 14-hydroxymorphinone General formula I (see graphic part) where R is allyl, cyclopropylmethyl; R' is chosen from the group consisting of acid residues of saturated or unsaturated carboxylic acids with 3-18 carbon atoms, by reacting the corresponding 14-hydroxymorphinan with allermuir agent selected from the group consisting of anhydrides of saturated or unsaturated carboxylic acids with 3-18 carbon atoms, in the environment of organic solvent in the presence of acceptor galgenwaard - carbonate or bicarbonate of an alkali metal, wherein the interaction is subjected to 10-35% an aqueous solution of N-substituted 14-hydroxymorphinan hydrochloride, the reaction of lead in the environment of water-immiscible chlorinated aliphatic hydrocarbon in the presence of an aqueous solution of acceptor galgenwaard.

2. The method according to p. 1, characterized in that use 10-20% solution of acceptor galgenwaard.

3. The method according to p. 1, characterized in that as a chlorinated hydrocarbon used methylene chloride, chloroform, dichloroethane, and trichloroethylene.

 

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The invention relates to organic chemistry, particularly to esters of N-substituted 14-hydroxymorphinone that are important narcotic analgesic and/or antagonistic means - opiate receptor blockers prolonged action and to methods for their preparation

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FIELD: chemistry.

SUBSTANCE: disclosed method of determining opium alkaloids involves extraction sample preparation carried out using a water-acetonitrile mixture with ratio of water to acetonitrile ranging from 38:12 to 42:8, as well as analysis of the obtained extract through high-performance liquid chromatography, carried out at wavelength 210 and 220 nm. The rate of extraction of alkaloids can be increased by adding mineral acid, for example orthophosphoric acid, to the extracting water-acetonitrile mixture.

EFFECT: shorter analysis time and fewer operations while preserving the degree of extraction of alkaloids.

3 cl, 9 dwg, 1 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds of general formula in which R1 represents C1-C10-alkyl with a straight or branched chain, optionally substituted by an aromatic ring, or -(CH2)nX(CH2)n- in which each n is equal to an integer from 0 to 2, X represents O, S, NH and where R2 represents H or C1-C6-alkyl with the straight or branched chain. Also, the invention refers to application of buprenophine derivative esters on a hydroxyl group of phenol for treating opiate dependences and/or moderate to strong pain, and to application as an agent releasing a therapeutic amount of buprenophine into a human body.

EFFECT: preparation of new buprenophine derivatives a hydroxyl group of phenol for treating opiate dependences and/or moderate to strong pain.

20 cl, 7 dwg, 1 tbl, 11 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to chemical-pharmaceutical industry, particularly a method for making the oxymorphone derivative naltrexone being an opiate antagonist by naltrexone processing by diazomethane in the presence of palladium acetate.

EFFECT: method eliminates using hardly accessible and expensive parent compounds, and it is characterised by ease of implementation.

3 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention declares a compound of structural formula (I) or its pharmaceutically acceptable salt, solvate or hydrate wherein: X is phenol opiate wherein a hydrogen atom of a hydroxyl phenol group of substituted by a covalent bond with -C(O)-Y-(C(R1)(R2))n-N-C(R3)(R4);Y is -NR5-, R5 is (C1-6)alkyl; n is equal to 2 or 3, each of R1 and R2 is independently hydrogen, alkyl or substituted alkyl; R3 is hydrogen or methyl; R4 is a residue of L-amino acid or a residue of their N-acyl derivatives, as well as Hydromorphone 3-(N-methyl-N-(2-N'-acetylarginine amino)ethyl carbamate, or their pharmaceutically acceptable salt. What is also specified is a method for preparing the compound of formula (I) or its pharmaceutically acceptable salt.

EFFECT: what is declared is a pharmaceutical composition controlling phenol opiate release and a method of pain management in a patient in need thereof involving the introduction of an effective amount of the composition.

19 cl, 20 ex, 12 tbl

FIELD: biotechnologies.

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EFFECT: improvement of medical treatment efficiency or prevention of drug abuse, drug withdrawal symptoms or pain relief.

10 cl, 11 ex, 4 tbl, 20 dwg

FIELD: medicine, pharmaceutics.

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.

In formula (I) double line, which contains from dotted line and solid line, represents double bond or single bond, R1 represents C4-C7-cycloalkylalkyl, R2 represents linear or branched C1-C5-alkyl, and B represents - CH=CH-.

EFFECT: invention also relates to compound of formula (I) and to method of treatment or prevention in case of disease(s) of biliary tracts, which are caused or intensified by sphincter of Oddi contraction.

6 cl, 1 dwg, 1 ex

FIELD: medicine.

SUBSTANCE: invention refers to a prodrug composition for treating diseases, disorders or conditions mediated by opioid binding to opioid receptors, containing a conjugate representing 3,6-diaspirin-hydromorphone in a pharmaceutically effective amount, and a biologically acceptable carrier. The invention also refers to a method of treating a patient suffering a disease, disorder or condition mediated by opioid binding to opioid receptors.

EFFECT: composition manifests improved bioavailability, lesser variability in an oral pharmacokinetic profile, lower peak plasma concentration and a lower probability of overdosage as compared to unconjugated hydromorphone.

12 cl, 21 dwg, 2 tbl, 7 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula KC-(II), use thereof in treating or preventing pain, method for production thereof, pharmaceutical compositions based thereon, single dose containing same, method for production thereof, method of identifying a compound of formula KC-(II), method of reducing potential abuse of composition containing a compound of formula KC-(II). In general formula KC-(II), Ra is hydrogen or hydroxyl; R5 is selected from (1-6C)alkyl and (1-6C) alkyl, substituted with (1-6C)alkxoycarbonyl group; each R1 is independently selected from hydrogen and (1-6C)alkyl; each R2 is independently selected from hydrogen, (1-6C)alkyl, and-C(O) NR21R22, where R21 and R22 are independently selected from a group consisting of hydrogen, (1-6C)alkyl and (1-6C)alkyl, substituted -C(O)OR60, where R60 is hydrogen; n equals a whole number from 2 to 4; R3 is hydrogen; R4 is , where each R6 is independently selected from hydrogen and (1-6C)alkyl, substituted guanidyl group or an amino group; W is -NR8-; R8 is hydrogen; p equals 1 or 2; and R7 is selected from acyl and acyl substituted with -COOH or-NHCOCH3.

EFFECT: novel pharmaceutical compositions.

18 cl, 20 dwg, 25 tbl, 41 ex

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16 cl, 17 dwg, 15 tbl, 49 ex

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