The method of obtaining n-carbethoxypyrrolidone-2

 

(57) Abstract:

Usage: as an intermediate product for the production of piracetam. The inventive product: N-carbethoxypyrrolidone-2, which is produced by the interaction of pyrrolidone-2 with sodium metal in toluene solution at the melting temperature of sodium and the molar ratio of pyrrolidone - 2: Na: toluene(1,0 - 1,5) : (1,0 - 1,1) : (8 - 15), the obtained reaction mixture containing Na-salt of pyrrolidone-2, act ethyl ester monochloracetic acid in their molar ratio(1,0 - 1,1) : (1,0 - 1,5) at room temperature. Yield 60 - 69%. table 2.

The invention relates to organic chemistry and relates to a method of obtaining N-carbethoxypyrrolidone-2, which is an intermediate product for the production of piracetam.

The demand piracetam has increased dramatically in recent years, which requires the development of relatively simple technological solutions related to all stages of its receipt.

A method of obtaining N-substituted 2-oxopyrrolidin (including N-carbethoxypyrrolidone-2) by cycloon - densitiy of acrylamido CH2= CHCONCH2R MeS(O) in MeSO for 3 h at room shall obtain the N-carbethoxypyrrolidone-2 (Ethyl-2-pyrrolidino - nacetate) the interaction of H2NCH2CO2Et and Br(CH2)3CO2Et, taken in a molar ratio of 2: 1 in solution WITH6H6for 5 h at 110aboutWith (patent Czechoslovakia N 217501, 1985). The process is carried out in an autoclave in periodic mode, which is the main disadvantage of this method from the point of view of its industrial implementation.

Known industrial method to produce N-carbethoxypyrrolidone-2 (N-ether"), currently used in the domestic industry [industrial regulation No. 93 for the production of piracetam, "Latvbithim" from 12.12.85, this method is the only method of obtaining N-carbethoxypyrrolidone-2 brought to the stage of industrial application, therefore it is selected as a prototype.

On the chosen method prototype the process of obtaining N-ether includes three stages:

1. Obtaining methyl sulfate o-methylbutyronitrile.

2. Obtaining on-methylbutyronitrile.

3. Obtaining N-carbethoxypyrrolidone-2 (N-ether").

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The described method has a number of disadvantages:

output N-ether in terms of pyrrolidone-2 is only 50%

the need to use toxic dimethylsulfate, dauser and the destruction of the salt of the lactam emitting trudnootdelyaemogo methyl chloride;

the long duration of the process (several days).

The claimed invention is directed to solving the task of creating a cost-effective environmentally friendly simplified industrial technology for N-ether. The technical result obtained by carrying out the invention, will consist in the organization of industrial production of N-ether with a higher yield than method-prototype (not less than 60%), and high content of the basic substance in technical N-ether, which will further ease the obtaining of piracetam.

The invention consists in the fact that used as source material pyrrolidone-2 interacts with metallic sodium in toluene solution at the melting temperature of sodium (100-105aboutC) and the molar ratio of pyrrolidone: Na: toluene, equal) 1,0-1,5):(1,0-1,1):(8-15), then the Na-salt of pyrrolidone-2 interacts with ethyl ether monochloracetic acid at a molar ratio of(1,0-1,1):(1,0-1,5) at room temperature, the reaction mixture is known technological methods produce N-air.

The first stage of the process of obtaining the Na-salt of pyrrolidone-2 in the environment of the solvent and active mixing rasplavlennykh intervals of process parameters allows to achieve high technical results, suitable for industrial application of the method.

Information confirming the possibility of carrying out the invention are given in examples of specific performance.

P R I m e R 1. In chetyrehosnuju flask with a capacity of 1 l equipped with a stirrer, thermometer, reflux condenser and addition funnel, was placed 500 ml (435 g) of toluene, then download 11,38 g of metallic sodium. Heated the reaction mixture to the melting point of sodium, include the stirrer. It generated suspen Ziya sodium in toluene was added dropwise 42,11 g of pyrrolidone-2, which corresponds to a ratio of pyrrolidone:Na:toluene 1:1:10. Within one hour, the sodium reacts with the formation of Na-salt of pyrrolidone-2 and the evolution of hydrogen ceases. The output of the Na-salt of pyrrolidone is 96% Then the reaction mixture is cooled to room temperature and dropwise metered 52,4 ml (72,73 g) ethyl ester monochloracetic acid within one hour. Toluene solution of N-ether is filtered off, suspended from NaCl or wash off with water from suspended dissolved impurities. Output N-ether, counting on the Na-salt of pyrrolidone-2, is 61%

Other examples of specific performance is similar to example 1, and their variables="ptx2">

As seen from the above examples, the compliance of the stated intervals of process parameters allows to obtain N-ether to yield not less than 60% (examples 1-3, 6, 7 PL. 2), a Violation of the stated interval of the ratio of components pyrrolidone in the direction of decreasing dramatically reduces the output PA-salt of pyrrolidone-2 in the first stage (example 4 of table. 1), and violation of it in the direction of increasing efficiency is impractical because entails an increase in the consumption of expensive and scarce pyrrolidone. Violation of the stated interval of the ratio of components in Na as downward and upward leads to a reduction of yield of Na-salt of pyrrolidone in the first stage of the process (examples 8, 9 PL. 1). The amount of solvent (toluene) almost no effect on the release of Na-salt of pyrrolidone-2; it is chosen on the basis of the consistency of the reaction mixture Na-salt of pyrrolidone-2. Practically found that it can vary with regard to the metallic sodium from 8 to 15, preferably this ratio is 12:1. Violation of the stated intervals of the ratios of components in the second stage as Na-salt of pyrrolidone, and ethyl ether monochloracetic acid leads to a marked reduction in yield N-ether (PR who I am, what pyrrolidone-2 is subjected to interaction with metallic sodium in toluene solution at the melting temperature of sodium and a molar ratio of pyrrolidone-2 Na toluene(1,0 1,5) (1,0 1,1) (8 15) and the resulting reaction mixture containing Na-salt of pyrrolidone-2, act ethyl ester monochloracetic acid at a molar ratio of Na salt of pyrrolidone-2 ethyl ether monochloracetic acid (1,0 1,1) (1,0 1,5) at room temperature.

 

Same patents:

)6-cyano-3,4-dihydro-2,2 - dimethyl-trans - 4-(2-oxo-1-pyrrolidinyl) -2h-1-benzopyran-3-ol" target="_blank">

The invention relates to organic synthesis and concerns a method for obtaining derived benzopyran representing () -6-cyano-3,4-dihydro-2,2-dimethyl-TRANS-4-(2-oxo-pyrrolidinyl)-2H - 1-benzopyran-3-ol of the formula VI

known as Cromakalim (DRL 34 915)

The invention relates to new cyclic imino-derivatives of General formula

In X And Y E (I) where a 2-pyrrolidinone or pyrrolin-2-it, unsubstituted or substituted residues R1and R2where R1means phenyl, unsubstituted or substituted by carboxyla, methoxycarbonyl, aminocarbonyl, methylaminoethanol, ethylaminoethanol, dimetilaminoflavonola, methanesulfonylaminoethyl or acetaminophe, alkyl with 1-4 carbon atoms, substituted by two phenyl groups, cyclohexyl, naptalam or phenyl, unsubstituted or substituted by fluorine, chlorine, bromine, hydroxyl, alkyl with 1-4 carbon atoms, alkoxyl with 1-4 carbon atoms, phenyl, vinylmation, benzyloxypropionic, methylsulfinyl, methylsulfonyl, trifluoromethyl, two chlorine atoms, two metaxylene groups, alkyl with 1-4 carbon atoms, unsubstituted or substituted by hydroxyl, metaxylem or fenoxaprop, moreover, these substituents are not in the position I, if R1linked to the nitrogen atom of the cycle And; methyl, substituted vinyl, carboxyla, methoxycarbonyl, aminocarbonyl, methylaminoethanol, ethylaminoethanol, dimetilaminoflavonola, benzylaminocarbonyl, pyrrolidinecarbonyl, piperidyl, methylaminopropane, arylaminopoly, AMI - nomation, dimethylaminopropoxy, carboxyla, methoxycarbonyl or dimetilaminoflavonola, if R1not linked to the nitrogen atom of the cycle; or sulfonyl, replaced by stands, dimethylaminopropoxy, phenyl or methoxyphenyl, if R1not linked to the carbon atom adjacent to the nitrogen atom of the cycle A, R2alkyl with 1-4 carbon atoms, unsubstituted or substituted phenyl;

In amino, aminomethyl and amidino, unsubstituted or substituted with one nitrogen atom by a benzyl, hydroxyl, methoxy group, cyano, one or two alkyl groups with 1-4 carbon atoms, alkoxycarbonyl with the total number of carbon atoms 2-5, benzyloxycarbonyl, phenoxycarbonyl or benzoyl, or two atoms of nitrogen amidinopropane linked using ethylene group, cyano, trimethylammonio, guanidino or guanidinate;

Y-E nonbranched alkyl with 2-5 carbon atoms, substituted carboxyla, methoxycarbonyl or stands, substituted vinyl, allyl, 1,2-Diocletian, carboxyla, phosphonopropyl, 0-methylphosphono, 0,0-dimethylphosphoric, oximation, alkoxycarbonyl with the total number of 2-7 carbon atoms, dimethylaminocarbonylmethyl is 1-3 carbon atoms in the CNS group, whereby phenyl may be substituted by one or two metaxylene groups, pyridinedicarboxylate, aminocarbonyl, unsubstituted or substituted by alkyl with 1-4 carbon atoms, biphenyloxy, replaced by carboxyla, carboxymethyl or methoxycarbonylmethyl, and the shortest distance between these substituents and the first nitrogen atom of the residue is at least 10 links;

X group of the formula

-X1X2X3X4X5where X1means a bond, methylene or ethylene, and if methylene not linked to the nitrogen atom of the cycle And then between the methylene and related balance X2may contain oxygen atom or sulfur, sulfonyl imino, -N(COCH3)-, -N(SO2CH3)-, -N(benzyl)-, -СОNH-, -NH-CO - or-NH-SO2- or between methylene and related balance X2can be imino, -N(benzyl) -, or-NH-CO-, and X1associated with the remainder of a, And X5with the rest IN;

X2nonbranched alkylen with 2-4 carbon atoms, albaniles with 2 or 3 carbon atoms and the double bond must not be adjacent to the heteroatom, phenylene, unsubstituted or substituted by fluorine, chlorine, bromine, stands, ethyl, trifluoromethyl, nitro-group, acetaminophe, meansville with 4-7 carbon atoms or bicycloalkyl to 7 carbon atoms;

X3bond, -CO-, -CO-NH -, or-NHCO-, if X3not directly followed by a heteroatom or a triple bond balance, and CO -,- CONH - and-NHCO - may not be adjacent to an aliphatic double bond of residue X2or an oxygen atom, sulfenyl, sulfinil, sulfonyl, oxymethylene, imino or sulfonylamino, if X2no aliphatic double bond at the end and for X3not directly followed by a heteroatom or a saturated carbon atom of the residue IN;

X4communication, the unbranched alkylene with 1-5 carbon atoms, phenylene, unsubstituted or substituted by fluorine, chlorine or stands, cycloalkyl with 4-7 carbon atoms;

X2together with X3and X4forms the unbranched alkylene with 3-6 carbon atoms, phenanthrene and naftilan, which may be fully or partially gidrirovanny, fluorenyl, in which the methylene may be replaced by oxymethylene or carbonyl, indaniel, endangerment or serialkiller from 8 to 11 carbon atoms;

X5link

) 6-cyano-3,4-dihydro-2,2 - dimethyl - trans-4- (2 - hydroxy-1 - pyrrolidinyl) -2h-1 - benzopyran-3 - ol" target="_blank">

The invention relates to organic synthesis and concerns a method for obtaining ()-6-cyano-3,4-dihydro-2,2-dimethyl-TRANS-4-(2-oxo - 1-1-pyrrolidinyl)-2H-1-benzopyran-3-ol formula

(I) known as Cromakalim

The invention relates to the field of production of new derivatives pyrrolidine General formula

Y-Rwhere Y represents - (CH2)n-, whereby n = 0;

X is a hydrogen atom, halogen or lower alkyl group;

R is a phenyl group, phenyl group involved halogen, lower alkyl, hydroxy - or alkoxygroup, trifluoromethyl, naftalina group, thiophene, unsubstituted or substituted lower alkyl, benzothiophen, pyridyl, imidazole, substituted lower alkyl when n = 1;

X is H or halogen,

R is phenyl, unsubstituted or substituted by halogen, hydroxy or alkoxygroup, lower alkyl; thiophene; Y represents S(O)pwhere p = 0 or 2, -O - or-NH; X is hydrogen,

R-phenyl;

having anti-hypertensive activity

FIELD: pharmaceutical chemistry, medicine.

SUBSTANCE: invention relates to new compounds of formula I ,

solvates or pharmaceutically acceptable salts having antiarrhythmic activity, including ventrical fibrillation, as well as pharmaceutical compositions containing the same. Compounds of present invention are useful in treatment or prevention of arrhythmia, modulation of ion channel activity, for topic or local anesthesia, etc. In formula I X is direct bond, -C(R6,R14)-Y- and C(R13)=CH-; Y is direct bond, O, S, and C1-C4-alkylene; R13 is hydrogen, C1-C6-alkyl, C3-C8-cycloalkyl, unsubstituted aryl or benzyl; R1 and R2 are independently C3-C8-alkoxyalkyl, C1-C8-hydroxyalkyl and C7-C12-aralkyl; or R1 and R2 together with nitrogen atom directly attached thereto form ring of formula II ,

wherein said ring is formed by nitrogen and 3-9 ring atoms selected independently from carbon, sulfur, nitrogen and oxygen, etc; R3 and R4 are independently attached to cyclohexane ring in 3-, 4-, 5-, or 6-position and represent independently hydrogen, hydroxyl, C1-C6-alkyl and C1-C6-alkoxy; and when R3 and R4 are bound with the same atom of cyclohexane ring they may form together 5- or 6-membered spiroheterocycle ring containing one or two heteroatoms selected from oxygen and sulfur; A is C5-C12-alkyl, C3-C13-carbocyclic ring, or ring structure as defined herein.

EFFECT: new antiarrhythmic drugs.

30 cl, 12 dwg, 34 ex

FIELD: organic chemistry, biochemistry.

SUBSTANCE: invention relates to substituted derivatives of N-phenyl-2-hydroxy-2-methyl-3,3,3-trifluoropropaneamide of the formula (I): wherein n = 1 or 2; R1 represents chlorine, fluorine, bromine atom, methyl or methoxy-group; R2 is taken among of one the following groups: (i) halogen atom, nitro-, hydroxy- amino- or cyano-group; (ii) -X1-R5 wherein X1 represents -O-, -S-, -SO-, -SO2-, NR6-, -CO-, -CONR6-, -NR6CO- wherein R6 represents hydrogen atom and R5 is taken among (C1-C6)-alkyl optionally substituted with one or some A, and so on; (iii) 4-8-membered heterocyclic group joined by nitrogen atom that represents saturated monocyclic ring comprising 4-8 carbon atoms among that at least one is nitrogen atom and so on; R3 represents (C1-C6)-alkyl optionally substituted with one or some A and so on; A is taken among hydroxy-, amino-group, halogen atom, carboxy-, N-(C1-C4-alkyl)-amino-, N,N-di-(C1-C4-alkyl)-amino-group, carbamoyl and (C1-C6)-alkoxy-group; D is taken among: (i) -Xa-Rc wherein Xa represents -SO2, -CO-, -NRdCO-, -NRd- or -CONRd-; (iv) cyano-group or halogen atom; (v) -XcRf wherein Xc represents -C(O)- and Rf represents 4-8-membered heterocyclic group joined by nitrogen atom that represents saturated monocyclic ring comprising 4-8 carbon atoms among that at least one is nitrogen atom with optionally additional heteroatom taken independently among oxygen atom (O), optionally substituted at ring carbon atom by the hydroxy-group, halogen atom, (C1-C4)-alkoxy-group, (C1-C4)-alkyl or cyano-group; G represents (C1-C6)-alkanoyl; R4 represents hydrogen or fluorine atom; or to its pharmaceutically acceptable salt or its ester hydrolyzed in vivo. Also, invention proposes a method for preparing compound of the formula (I). Also, invention proposes pharmaceutical composition enhancing activity of pyruvate dehydrogenase comprising substituted derivatives of N-phenyl-2-hydroxy-2-methyl-3,3,3-trifluoropropaneamide of the formula (I) or its pharmaceutically acceptable salt or ester hydrolyzed in vivo in combination with pharmaceutically acceptable vehicle or carrier. Invention provides preparing derivatives of N-phenyl-2-hydroxy-2-methyl-3,3,3-trifluoropropaneamide enhancing activity of pyruvate dehydrogenase.

EFFECT: valuable medicinal and biochemical properties of compounds.

14 cl, 1 tbl, 85 ex

FIELD: organic chemistry, biochemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new inhibitors of farnesyltransferase of the formula (I):

wherein R1 means hydrogen atom (H), group of the formula R5C(O)- wherein R5 means phenyl, pyridyl or N-methylpiperidine; R2 means hydrogen atom (H), isopropyl, cyclopentyl or N-methyltetrahydropyridyl; R3 means hydrogen atom (H), halogen atom; R4 means hydrogen atom (H), halogen atom; L means -CH2-Z- wherein Z means NH; Y means sulfur atom (S), S(O) or S(O)2; or its salt. Compounds of the formula (I) inhibit activity of enzyme, farnesyl(protein)transferase, that allows their using in pharmaceutical composition in cancer treatment.

EFFECT: valuable medicinal properties of inhibitors.

18 cl, 3 tbl, 3 sch, 6 ex

New compounds // 2261245

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new compounds of the formula (I): wherein m = 0, 1, 2 or 3; each R1 represents independently halogen atom, cyano-group, hydroxyl, (C3-C6)-cycloalkyl, (C1-C6)-alkoxy-group, (C1-C6)-halogenalkyl, (C1-C6)-halogenalkoxy-group, -NR9R10, (C3-C6)-cycloalkylamino-, (C1-C6)-alkylthio-, (C1-C6)-alkylcarbonylamino-group or (C1-C6)-alkyl; X represents -O- or CH2-, OCH2-, CH2O-, CH2NH-, NH-; Y represents nitrogen atom (N) or group CH under condition that when X represents -O- or CH2O-, CH2NH- or NH-group then Y represents group CH; Z1 represents a bond or group (CH2)q wherein q = 1 or 2; Z2 represents a bond or group CH2 under condition that both Z1 and Z2 can't represent a bond simultaneously; Q represents -O- or sulfur atom (S) or group CH2 or NH; R2 represents group of the formula: n = 0; each R4, R5, R6 and R7 represents independently hydrogen atom (H), (C1-C6)-alkyl either R4, R5, R6 and R7 represent in common (C1-C4)-alkylene chain joining two carbon atoms to which they are bound to form 4-7-membered saturated carbon ring, either each R5, R6 and R7 represents hydrogen atom, and R4 and R8 in common with carbon atoms to which they are bound form 5-6-membered saturated carbon ring; R8 represents hydrogen atom (H), (C1-C6)-alkyl or it is bound with R4 as determined above; each R9 and R10 represents independently hydrogen atom (H), (C1-C6)-alkyl; R15 represents (C2-C6)-alkyl, (C2-C6)-alkenyl, (C3-C6)-cycloalkyl, (C5-C6)-cycloalkenyl, adamantyl, phenyl or saturated or unsaturated 5-10-membered heterocyclic ring system comprising at least one heteroatom taken among nitrogen, oxygen and sulfur atoms wherein each group can be substituted with one or more substitute taken independently among nitro-group, hydroxyl, oxo-group, halogen atom, carboxyl, (C1-C6)-alkyl, (C1-C6)-alkoxy-, (C1-C6)-alkylthio-group, (C1-C6)-alkylcarbonyl, (C1-C6)-alkoxycarbonyl, phenyl and -NHC(O)-R17 under condition that R15 doesn't represent unsubstituted 1-pyrrolidinyl, unsubstituted 1-piperidinyl or unsubstituted 1-hexamethyleneiminyl group; t = 0, 1, 2 or 3; each R16 represents independently halogen atom, cyano-group, hydroxyl, (C3-C6)-cycloalkyl, (C1-C6)-alkoxy-group, (C1-C6)-halogenalkyl, (C1-C)-halogenalkoxy-group, -NR18R19, (C1-C6)-cycloalkylamino-, (C1-C6)-alkylthio-, (C1-C6)-alkylcarbonylamino-group, (C1-C6)-alkyl; R17 means (C1-C6)-alkykl, amino-group, phenyl; each R18 and R19 means independently hydrogen atom (H), (C1-C6)-alkyl, or its pharmaceutically acceptable salt or solvate. Compounds of the formula (I) elicit activity of a modulating agent with respect to activity of chemokine MIP-1α receptors that allows their using in pharmaceutical composition in treatment of inflammatory diseases.

EFFECT: valuable medicinal properties of new compounds.

14 cl, 98 ex

FIELD: organic chemistry, biochemistry.

SUBSTANCE: invention relates to compounds that inhibit binding ligands with α4β1-integrin (VLA-4) selectively. Compounds have the formula (I):

wherein W means unsubstituted phenyl or phenyl substituted with 1-3 substitutes taken among (C1-C6)-alkyl, halogen atom, (C1-C4)-alkoxy-group and halogen alkyl; W1 means unsubstituted phenylene or phenylene substituted with 1-3 substitutes taken among (C1-C6)-alkyl, halogen atom and (C1-C4)-alkoxy-group, pyridylene, pyridylene substituted with 1-3 substitutes taken among (C1-C6)-alkyl, halogen atom and (C1-C4)-alkoxy-group, 2-oxopyrrolylene or thiazolylene; A means oxygen atom (O); R means -(CH2)n- wherein n = 1 or 2; X means -C(O)-; M is taken among the following groups: a)

wherein means divalent 5- or 6-membered heterocyclic radical wherein nitrogen atom is located in the joining point to X wherein Q represents -CH2-, -O- or -S-; R1, R2 and R3 are taken independently among the group involving: hydrogen atom (-H), hydroxyl group (-OH), quinolinyloxy-group, -NH2, mono- or dialkylamino-group, (C1-C6)-alkylsulfonylamino-, arylsulfonylamino-, naphthyloxy-, phenyloxy-group substituted optionally with di-(C1-C6)-alkylamine, (C1-C6)-alkyl, benzyloxymethyl, halogen atom, phenyl, (C1-C4)-alkoxy-group; or two adjacent R1, R2 and R3 taken in common can form alkylene- or alkylenenedioxy-group substituted optionally with 1-3 alkyl groups; R4 means hydrogen atom (H), lower alkyl; Y is taken among a bond, (C2-C8)-alkenylene group, (C2-C8)-alkynylene group, -C(O)-, -C(O)NH- and -(CH2)kY2 wherein k is taken among 1, 2 and 3; Y2 means a direct bond or divalent radical taken among -O-, -S-, -S(O)-, -S(O)2- and -NY3- wherein Y3 is taken among hydrogen atom (H), lower alkyl; Z means (C3-C8)-cycloalkylene, optionally substituted phenylene, pyridylene, piperidylene, piperazinylene; A1 means a direct bond, -(CH2)t-alkynyl wherein t is taken among 1, 2 and 3; R5 means -OH, lower alkoxy-group, , ; b) means wherein R11 is taken among , -NR12- wherein R12 is taken among hydrogen atom (-H), optionally substituted lower alkyl, lower alkenyl, lower alkynyl, phenyl; Z3 is taken among a direct bond, (C1-C12)-alkyl wherein one or some carbon atoms can be replaced with -O- or -NR13- wherein R13 means hydrogen atom (-H), lower alkyl, wherein x = 0 or 1; y = 1, 2 or 3; R14 means hydrogen atom (-H), ; and when R11 means NR12 then Z3 is taken among: wherein 14Ra means hydrogen (H), halogen atom; , and ; Q2 means wherein R17 and R18 mean hydrogen atom (H), lower alkyl; or phenylene that can be substituted; L1 means -COOH or -COOR19 wherein R19 means lower alkyl. Compounds of the formula (I) inhibit activity of VLA-4-mediated adhesion of cells that allows their using in pharmaceutical compositions.

EFFECT: valuable medicinal properties of compounds and compositions.

21 cl, 11 tbl, 283 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new compounds including all its enantiomeric and diastereomeric forms, and to their pharmaceutically acceptable salts wherein indicated compound corresponds to the formula: wherein A represents a conformationally limited ring system chosen from the group comprising the following formulae: (a) (d) and (e) wherein carbon atoms labeled by asterisks can be in any stereochemical configuration or their mixtures wherein Y has a formula: -(CH2)b-R15 wherein index b = 1-4, and R15 represents -OH, -NH2, guanidine-group, and Z has a formula: wherein R represents hydrogen atom; R9 represents naphthylmethyl; R10 represents -C(X)N(R16)2 wherein each R16 represents independently hydrogen atom or (C1-C10)-alkyl; X represents oxygen atom; or Z represents naphthylmethyl wherein W has a formula: wherein R represents phenyl substituted optionally with halogen atom of OH-group wherein fragment L is chosen from the group comprising: -NH- or -NHC(O)-; B represents hydrogen atom of fragment of the formula: wherein fragments R2, R3 and R4 are chosen independently among the group comprising hydrogen atom, -NHC(O)CH3, benzyl substituted optionally with hydroxy-group or halogen atom, imidazolylmethyl; or fragments R2, R3 and R represent in common naphthalinyl or isoquinolinyl; or one radical among R2, R3 and R4 represents hydrogen atom and two radical among R, R3 or R4 chosen in common form piperidine ring or tetrahydroisoquinoline ring substituted optionally with the group -C(O)CH3. Also, invention relates to a pharmaceutical composition possessing the agonistic activity with respect to MC-3/MC-4 receptors based on these compounds. Invention provides preparing new compounds and pharmaceutical compositions based on thereof for aims in treatment of disorders mediated by function of MC-3/MC-4 receptors.

EFFECT: valuable medicinal properties of compounds and compositions.

17 cl, 14 tbl, 12 ex

FIELD: organic chemistry, chemical technology, biochemistry, medicine.

SUBSTANCE: invention relates to novel isoquinoline compounds of the general formula (I): wherein R1 represents hydrogen atom, halogen atom or alkyl; Y is absent or represents alkylene chain comprising from 1 to 8 carbon atoms wherein arbitrary carbon atom can comprise hydroxyl group as a substitute; R represents the following formula (II): wherein X represents -CH or nitrogen atom under condition that if Y absent in the formula (I) then X must represent -CH; W represents -CH or nitrogen atom under condition that if X represents -CH then W must represents nitrogen atom; s represents a whole number from 1 to 3; t represents a whole number from 1 to 3; if R3 represents hydrogen atom or alkyl then R2 represents hydrogen atom, alkyl, hydroxyl group or hydroxyalkyl, and R2' represents hydroxyl group or hydroxyalkyl, and if R3 represents hydroxyalkyl then R2 and R2' represent hydrogen atom. Also, invention relates to their optically active forms, pharmaceutically acceptable salts, aqueous adducts, hydrates and solvates. Compounds of the formula (I) elicit inhibitory effect on activity of poly-(ADP-ribose)-polymerase and can be used in prophylaxis of diseases associated with cerebral infarction.

EFFECT: valuable medicinal properties of compounds, improved method of synthesis.

40 cl, 4 tbl, 55 ex

FIELD: organic chemistry, chemical technology.

SUBSTANCE: invention relates to a method for synthesis of N-methyl-N-{(1S)-1-phenyl-1-[(3S)-3-hydroxypyrrolidin-1-yl]ethyl}-2,2-diphenylacetamide. Method involves the following steps: (a) interaction of N-substituted derivative of phenylglycine of the formula (I): , wherein R means -OR1, -SR1; R1 means A, benzyl, unsubstituted phenyl or phenyl, biphenyl or naphthyl mono- or disubstituted with halogen atom, -OA or (C1-C6)-alkyl; A means linear or branched (C1-C6)-alkyl; M means hydrogen atom (H) or a cation chosen from group comprising alkaline metals, earth-alkaline metals, ammonium or alkylammonium with compound of the formula (II): , wherein R2 means H, A, or with acid-additive salt of compound of the formula (II) of acids HCl, HBr, HJ, H2SO4, H3PO4, or with organic carboxylic acid to obtain compound of the formula (III): , wherein R and R2 have above given values; (b) synthesized compound is converted to compound of the formula (IV): , by reduction reaction that is converted optionally to acid-additive salt of acids HCl, HBr, HJ, H2SO4, H3PO4, or to salt of organic carboxylic acid, and (c) synthesized compound of the formula (IV) is subjected for interaction with activated carboxylic acid of the formula (V): , wherein R4 means F, Cl, Br, J, -OA or -O-CO-A to yield compound of the formula (VI): , that is converted to a corresponding acid-additive salt using inorganic acid chosen from group comprising HCl, HBr, HJ, sulfuric acid, sulfamic acid, nitric acid, phosphoric acid, ortho-phosphoric acid or using organic acid.

EFFECT: improved method of synthesis.

7 cl, 8 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel derivatives of pyrrolidinium of the general formula (I): possessing antagonistic effect with respect to muscarinic receptors M3 wherein B means phenyl or thienyl group; each radical among R1, R2 and R means independently hydrogen, fluorine, chlorine atom or hydroxyl; n means a whole number from 0 to 1; A means group chosen from groups -CH2 and -O-; m means a whole number from 0 to 6; R means (C1-C8)-alkyl; X- represents a pharmaceutically acceptable anion of mono- or multibasic acid, and involving all separate stereoisomers and their mixtures. Also, invention relates to methods for synthesis of such compounds, pharmaceutical compositions containing such compounds and to their using in therapy as antagonists of muscarinic receptors M3.

EFFECT: valuable medicinal properties of compounds and pharmaceutical compositions.

17 cl, 51 ex

FIELD: chemistry.

SUBSTANCE: invention relates to new compounds of the formula (IE) or of its pharmaceutically acceptable salt, stereoisomer, stereoisomeric mixture, geometric isomer, including its chosen enantiomeric, diastereomeric and geometric isomers and their mixtures, where R4 and R5 are independently selected from C1-C6 alkoxy.

EFFECT: it makes it possible to use them in the pharmaceutical compositions and the methods of blocking Na channels in warm-blooded animals.

18 cl, 5 tbl, 18 ex

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