The method of obtaining derivatives benzhydrylpiperazine
(57) Abstract:The inventive product is derived benzhydrylpiperazine f-ly 1, where R1-H, Hal, lower alkyl, lower alkoxy, trifluoromethyl; R2-H, Hal; R3-H, Hal, CF3; n is an integer from 2 to 6, R4and R5- one N other benzoyl, substituted NO2or CH3O or R4and R5together with the nitrogen atom to which they are attached, heterocyclic group, such as Succinimidyl, 4-phenylsuccinic, 2 - oxopentanenitrile, 3 - benzyl-2 - oxopentanenitrile,1,2,3,4 - tetrahydro-2,4 - diorskin - Azzolini,3,4-dihydro-4 - oxothiazolidine,3,4 - dihydro-4-oxo-2-metilfentanil, 3,7-dihydro-1,3-dimethyl - 2,6-dioxo-1H-purinol, 3,7-dihydro-3,7-dimethyl-2,6-dioxo-1H-purinol. Reagent 1: Amin f-crystals X-(CH2)n-NR4R5where x-Ha1, tosyl. Reagent 2: benzhydrylpiperazine. Reaction conditions: excess reagent specified amine, aprotic solvent. The compounds possess anti-histamine activity without side sedative action. Connection structure of f-crystals 1 2 tab. The invention concerns a method of obtaining new derived benzhydrylamine-piperazine, which can find application in medicine.Known production, lcil, alkoxy or halogen, Rllrepresents hydrogen or alkyl, the group NRll" Rll' means substituted group dialkylamino, alkylamino, pyrrolidino, piperidino, morpholino or piperazine derivatives. These compounds act on the Central nervous system and, in particular, have a sedative effect. [Cm. the following documents: -BURGER, MEDICINAL CHMISTRY 4th edition, volume III, Manfred WOLFF, pages 559-564 WIL EYN.Y. Eds I. M. MELON and A. BuZAS Fr 74.23.262 and Fr 76.13.592-GOOTIES I. and E. Coll R. 0.099.148]
The purpose of the invention to develop new compounds that have anti-histamine activity, identical to or exceeding antihistaminics activity called derivatives, but do not have a sedative action.This goal is achieved by the proposed method of obtaining derivatives benzhydrylamine-piperazine of General formula I
< / BR>where R1hydrogen, halogen, lower alkyl, lower alkoxy or cryptomaterial;
R2hydrogen or halogen;
R3hydrogen, halogen or cryptomaterial;
n is an integer between 2 and 6 inclusive;
R4and R5represent one of a hydrogen atom and the other group of benzoyl, substituted nitro or methoxy, or R4and R5form together with the nitrogen atom to which they are Holy the sludge, 3-benzyl-2-oxopentanenitrile, 1,2,3,4-tetrahydro-2,4-dioxopiperazinyl, 3,4-dihydro-4-oxothiazolidine, 3,4-dihydro-4-oxo-2-metilfentanil, 3,7-dihydro-1,3-dimethyl-2,6-dioxo-1H-purinol, 3,7-dihydro-3,7-dimethyl-2,6-dioxo-1H-PU - rinil, characterized in that the compound of General formula II
X-(CH2)n-N where n, R4and R5have certain values and X represents the group of halogen or Totila, is subjected to the interaction with the excess benzhydrylamine-piperazine of General formula III
-(CH2)2-NNH where R1-R3have the values given in inert aprotic solvent, such as toluene, and, if necessary, the obtained target product is converted into the acid additive salt.Acid additive salts of the compounds according to the invention receive a classical way by interacting with pharmaceutically acceptable acids, such as, for example, acetic acid, hydrochloric acid, corporationa acid, methansulfonate.Compounds according to the invention have valuable pharmacological properties, in particular, antihistaminics and antispasmodic properties and can be used in particular for the treatment of spasmodic States and al the magnetic resonance and infrared spectrum, as well as their elemental analysis.P R I m e R 1. 1-[2-(Benzhydryl)ethyl]-4-[2-(phthalimido)ethyl]piperazinediones-lifenet (formula I, R1=R2=R3=H;
NR4R5= - n=2;)
Charged to the reactor and 15.3 g of bromoethylamine, 36 g benzhydrylamine-piperazine, 500 mg of potassium iodide in 250 ml of anhydrous toluene. The reaction mixture is heated for 6 h to 120aboutC. Absorb the residue 100 ml of water, extracted with 100 ml of toluene. Dried and evaporated solvents. This way obtain 27 g of oil which crystallized from ethanol. Solid dehydrate and get to 25.5 g of crystals (So pl. 101aboutC).To those of 25.5 g of the obtained solid substance dissolved in 100 ml of acetone, added to 10.5 g methansulfonate. Dehydrate and get that through 34 g dimethanesulfonate (So pl. 124aboutC) empirical formula:
Calculated With 59,26; N 5,94; N 6.35mm; S RS 9.69.Found, 59,24; N. Of 5.99; N 6,36; S 9,79.An NMR spectrum (base in solution in CDCL3, ethanol TM):
of 7.6 ppm (m) 4H, (phthalimido); and 7.1 ppm (m, 10H, (f2C);
at 5.3 ppm (S, 1H, (CH-0); and 3.8 ppm (t), 2H (CH2-N-C=0);
the 3.5 ppm (t, 2H, (CH2-0); 2,5 ppm (m), N, (CH
The reactor is placed to 8.4 g of N-(2-bromo-ethyl)-3,4-dihydro-2,4-dioxo-2H-1,3-benzo - Kazyna (0,0311 mol), 18,4 benzhydrylpiperazine In (0,0622 mol) and 250 mg of potassium iodide in 150 ml of toluene. The reaction mixture is heated for 6 h at 120aboutAnd hydrolyzing the residue 100 ml of water, decanted and again the aqueous phase is extracted with 50 ml of toluene. Dried toluene fractions are combined and the solvent is evaporated. Thereby obtaining 16 g of crude oil, which is purified by chromatography on a column of silica gel. The pure product is isolated and receive of 6.65 g of the target product. To those of 6.65 g of oil dissolved in acetone (50 ml) was added 2,3 equivalent methansulfonate. The crystals are sucked off and thus receive 7,8 g dimethanesulfonate gross formula
WITH28H33N3O32CH3SO3H.An NMR spectrum (solvent Dl3; ethanol TMS)
2,2 2,9 (m), N, CH2N; 3,4 (t), 2H,O-CH2; 3.6(t), 2H, CH2-N-SN; 5,2(S), 1H, CH 0; 6,5 8,1(m), 14N, arene. 7,6 (m), 1H, NH; and 9.2 (m, 1H, HE.Acting on enaleni below.5 2.1 2.7 (m), N, CH2-N; 3.4 (t, 2H, CH2-ON;
3.5 (s, 3H, CH3-O; 3.6 (t, 2H, CH2-N - C=O;
5.1 (s, 1H, CH-O; 6.7 (m, 4H, arom;
7.0 (s), 5H, arene; 7.1-7.8 (m, 4H, arene.8 2.3-2.7 (m, 12H, CH2-N; 3.5 (t, 2H, O-CH2;
3.7 (t, 2H, CH2-N-C=0; 5.2 (s, 1H, CH-O;
7.0-7.4 (m, 4H, arene; 3.0-7.6 (m, 4H, CH2-N-C=0.14 2.2-2.7 (m, 12H, CH2-N; 3.5 (t, 2H, O-CH2;
3.7 (t, 2H, CH2-N-C=O; 5.3 (s, 1H, CH-O;
6.9-7.8 (m, 12H, arene.16 1.4-1.9 (m, 4H, C-CH2-CH2-C;
2.1-2.7 (m, 12H, CH2-N; 3.5 (t, 2H, CH2-O.3.6 (t) 2H, CH2-N-C=O; 5.2 (s, 1H, CH-O;
7.1 (m, 10H, arene. 7.3-7.6 (m, 4H, arene.17 1.0-1.9 (m, 6H, C(CH2)3-C; 2.0-2.8 (m, 12H, CH2N;
3.4 (t, 2H, CH2-O; 3.5 (t, 2H, CH2-N - C=O;
5.1 (s, 1H, CH-O; 7.0 (s), 10H, arene;
7.2 and 7.6 (m) 4H, arene.18 1.1-1.8 (m, 8H, C-(CH2)4 C; 1.9-2.7 (m, 12H, CH2-N3.4(t); 2H, CH2-O; 3.5 (t, 2H, CH2-N - C=O;
5.1 (s, 1H, CH-O; 7.0 (s) 10H, arene;
7.2-7.6 (m, 4H, arene.24 2.2-2.8 (m, 12H, CH2-N; 3.4 (t, 2H, CH2-O
3.9(t), CH2-N-C; 5.2 (s, 1H, CH-O; 6.9 (s), 10H, arene;
6.8-8.0 (m, 5H, arene.25 2.2-2.6 (m, 12H, CH2-N; 2.4 (s, 3H, CH3;
3.4 (t, 2H, O-CH2;
3.9 (t, 2H, CH2-N-C;
5.1 (s, 1H, CH-O; 7.0 (s), 10H, arene;
6.8-8.0 (m, 4H, arene.27 2.1-2.7(m, 12H, CH2-N; 3.4(t, 2H, CH2-O2.7(m), 12H, CH2N;
3.4(t, 2H, CH2-O; 3.8(t, 2H, CH2-N-C;
5.1(s, 1H, CH-O;
6.6-7.2(m, 15H, arene, NH.30 2.3-3.0(m, 12H, N-CH2; 3.2(s, 3H, N-CH3;
3.3(t, 2H, CH2-O; 3.4(s, 3H, N-CH3;
4.2(t, 2H, CH2-N; 5.2(s, 1H, CH-O;
7.0(s), 10H, arene; 7.3(s, 1H, CH=n31 1.2-1.9(m, 4H, C-(CH2)2-C; 2.0-2.4(t, 2H, CH2N;
3.2(s, 3H, CH3-N; 3.3(t, 2H, CH2-O;
5.1(s, 1H, CH-O; 7.1(s), 10H, arene; 7.9(s, CH=n38 1.2-2(m), 4H, C-CH2-CH2-C; 2.1(s, 3H, CH3(arom);
2.3-2.7(m, 12H, CH2-N; 3.3(s, 3H, CH3N;
3.4(t, 2H, CH2-O; 4.2(t, 2H, CH2N;
5.1(s, 1H, CH-O; 7.0(m, 9H arene;
7.2(s, 1H, CH=N
39 1.2-1.9(m, 4H, C-CH2-CH2-C;
2.3-2.8(m, 12H, CH2-N; 3.3(s, 3H, CH3N;
3.4(t, 2H, CH2-O; 3.5(s, 3H, CH3N;
4.2(t, 2H, CH2-N; 5.3(s, 1H, CH-O;
6.9(m), 4H, arene; 7.1(s), 5H, arene;
7.4(s, 1H, CH=N
42 1.3-2(m), 4H, C-CH2-CH2-C; 2.3-2.6(m, 12H, CH2N;
3.3(s, 3H, CH2-N; 3.4(t, 2H, CH2-O;
3.5(s, 3H, CH3-N; 4.2(t), CH2-N; 5.2(s, 1H, CH-O;
7.1(m, 8H, arene; 7.4(s, 1H, CH=n43 1.2-2.0(m, 4H, C-CH2-CH2-C
2.3-2.8(m, 12H, CH2-N; 3.2(s, 3H, CH3N;
3.3(t, 2H, CH2-O; 3.4(s, 3H, CH3N;
3.6(s, 3H, CH3-O; 4.1(t, 2H, CH2N;
5.1(s, 1H, CH-O; 6.7(m), 4H, arene; 7.0(s, 9H, arene.44 2.3-2.7(m, 12H, CH2-N, 3.3(s, 3H, CHP CLASS="ptx2">Description of the pharmacological tests
Locomotor activity of mice was determined using the PV actimetry Boisse and Simon.Put five mice in a box, closed the lid, passing through it in two perpendicular beams of light that mouse was crossed when moving.These movements were calculated by the computer in thirty minutes and one hour.Strap with holes.After 30 min after intraperitoneal administration of the derivatives corresponding to the invention, each mouse was placed for 5 min on an automated bar with holes, and noted in the minutes number of surveyed holes.Effective dose 50 is calculated as a function of the obtained results.Phenylbenzophenone (FBH).Pain in the peritoneum of mice is called intraperitoneal injection phenylbenzophenone (FBH). The decrease of pain syndrome characterized by crooked position of the animal examined by injection of the test product for 30 min prior to the introduction of FBH.Effective dose 50 is calculated as a function of the percentage of attenuation of pain syndrome to control animals.The test substance is introduced party of Guinea pigs for 30 minutes until the new placing them in the chamber for controlling the resistance to histamine. The Guinea pig is considered protected if it can withstand ten minutes remaining in the aerosol of histamine, without signs of asphyxia.The average effective dose is calculated as a function of the obtained results.Anti-histamine activity.Determined the dose that protects 50% of the Guinea pigs regarding lethal dose of histamine.The product is introduced for 30 minutes before intravenous injection of hydrochloric acid histamine. Effective dose 50 is calculated as a function of the obtained results.The results are shown in table. 2. The METHOD of OBTAINING DERIVATIVES BENZHYDRYLPIPERAZINE General formula
< / BR>where: R1hydrogen, halogen, lower alkyl, lower alkoxy or cryptomaterial;
R2hydrogen or halogen;
R3hydrogen, halogen or cryptomaterial;
R4and R5one hydrogen, the other group of the benzoyl is clichesque group, selected from the group: Succinimidyl, 4-phenylsuccinic, 2-oxopentanenitrile, 3-benzyl-2-oxopentanenitrile, 1,2,3,4-tetrahydro-2,4-dioxoimidazolidin, 3,4-dihydro-4-oxothiazolidine, 3,4-dihydro-4-oxo-2-metilfentanil, 3,7-dihydro-1,3-dimethyl-2,6-dioxo-1H-purinol, 3,7-dihydro-2,7-dimethyl-2,6-dioxo-1H-purinol,
characterized in that the compound of General formula
< / BR>where n, R4and R5have the specified values;
X group is a halogen or Totila,
subjected to interaction with excess benzhydrylamine-piperazine of General formula
< / BR>where R1R3have the specified values,
in inert aprotic solvent, such as toluene, and, if necessary, the obtained target product is converted into the acid additive salt.
FIELD: organic synthesis.
SUBSTANCE: invention provides substituted methyl-N-amidooxamoyl-N-phenyl-D,L-alaninates having general formula I:
where R1 and R2 represent C1-C4-alkyl, R3 and R4 either represent H, C1-C6-alkyl or form together group -(CH3)2-X-(CH2)2- wherein X is O or CH2. Compounds exhibit fungicide activity and can be used to prevent and treat plant diseases.
EFFECT: increased choice of fungicides.
5 cl, 1 tbl, 11 ex
FIELD: organic chemistry, pharmaceutical compositions.
SUBSTANCE: invention relates to N-(indolcarbonyl)piperazine derivatives of general formula I
, wherein R1 is optionally substituted phenyl or naphthyl; R2 and R3 are independently Hal or Het1, A, OA, CN; R4 is H, CN, acyl, Hal, CONH2, CONHA or CONA; R1 is H; or R4 and R5 together form C3-C5-group; Het1 is aromatic heterocyclic ring, optionally substituted with one or two halogen atoms and containing 1-3 similar or different heteroatoms such as nitrogen, sulfur and oxygen, A-(C1-C6)-alkyl; Hal is F, Cl,Br, and J; and indole ring may be substituted with isatin, except for (1H-indole-5-yl)-(4-phenethylpiperazine-1-yl)-methanone and 1-((5-methoxy-1H-indole-7-yl)-carbonyl)-4-(2-phenethyl)-piperazine. Claimed compounds are potent 5-HT2A antagonists and are useful in treatment of psychosis, schizophrenia, depression, neurological diseases, dismepodia, Parlinson's disease, Alzheimer's disease, Hungtington's disease, amyotrophic lateral sclerosis, bulimia or anorexia, premenstrual syndrome, and/or in alleviation of hypomania.
EFFECT: new pharmaceutical agents.
9 cl, 10 ex, 1 tbl
FIELD: organic chemistry, medicine, pharmacy.
SUBSTANCE: invention relates to derivatives of adamantane of the general formula:
wherein m = 1 or 2; each R1 represents independently hydrogen atom; A represents C(O)NH or NHC(O); Ar represents the group:
wherein X represents a bond, oxygen atom or group CO, (CH2)1-6, CH=, O(CH2)1-6, O(CH2)2-6O, O(CH2)2-3O(CH2)1-3, CR'(OH), NR5, (CH2)1-6NR5, CONR5, S(O)n, S(O)nCH2, CH2S(O)n wherein n = 0, 1 or 2; R' represents hydrogen atom; one of R2 and R3 represents halogen atom, nitro-group, (C1-C6)-alkyl; and another is taken among R2 and R3 and represents hydrogen or halogen atom; either R4 represents 3-9-membered saturated or unsaturated aliphatic heterocyclic ring system comprising one or two nitrogen atoms and oxygen atom optionally being heterocyclic ring system is substituted optionally with one or more substitutes taken independently among hydroxyl atoms, (C1-C6)-alkyl, (C1-C6)-hydroxyalkyl, -NR6R7, -(CH2)rNR6R7; or R4 represents 3-8-membered saturated carbocyclic ring system substituted with one or more substitutes taken independently among -NR6R7, -(CH2)NR6R7 wherein r = 1; R5 represents hydrogen atom; R6 and R7 each represents independently hydrogen atom or (C1-C6)-alkyl, or (C2-C6)-hydroxyalkyl group eliciting antagonistic effect with respect to R2X7-receptors. Also, invention describes a method for their preparing, pharmaceutical composition comprising thereof, a method for preparing the pharmaceutical composition and their applying in therapy for treatment of rheumatic arthritis and obstructive diseases of respiratory ways.
EFFECT: improved method for preparing and treatment, valuable medicinal properties of compounds.
13 cl, 88 ex
FIELD: organic chemistry, medicine.
SUBSTANCE: invention relates to compounds of formula I , wherein G is carbon or nitrogen atom; A is i) phenyl substituted with any from -COOH, -CONH2, COOCH3, -CN, -NH2 or -COCH3; ii) naphthyl, benzophuranyl, and quinolinyl; and iii) formulae , , .
Compounds of present invention are useful in particular in pain treatment.
EFFECT: new agents for pain treatment.
FIELD: organic chemistry, medicine, pharmacy.
SUBSTANCE: invention relates to novel soluble pharmaceutical salts formed from salt-forming active compound of the general formula (I) or (II) and sugar substitute that can be used in preparing medicinal agents useful in pain and enuresis treatment. Salt-forming active substance represents a salt-forming compound among 1-phenyl-3-dimethylaminopropane compounds of the general formula (I) wherein X means -OH, F, Cl, H or group -OCOR6; R1 represents (C1-C4)-alkyl group; R2 represents H or (C1-C4)-alkyl group; R3 represents H or (C1-C4)-alkyl group with a direct chain, or R2 and R3 form in common (C4-C7)-cycloalkyl group and if R5 means H then R4 represents group O-Z in meta-position wherein Z means H,(C1-C3)-alkyl, -PO-(O-C1-C4-alkyl)2, -CO-(O-C1-C5-alkyl), -CONH-C6H4-(C1-C3-alkyl), -CO-C6H4-R7 wherein R7 represents -OCO-C1-C3-alkyl in ortho-position or group -CH2N(R8)2 in meta- or para-position and wherein R8 means (C1-C4)-alkyl or 4-morpholino-group, either R4 represents S-(C1-C3)-alkyl in meta-position, meta-Cl, meta-F, group -CR9R10R11 in meta-position wherein R9, R10 and R11 mean H or F, group -OH in ortho-position, O-(C2-C3)-alkyl in ortho-position, para-F or group -CR9R10R11 in para-position wherein R9, R10 and R11 mean H or F, or if R5 means Cl, F, group -OH or O-C1-C3-alkyl in para-position then R4 means Cl, F, group -OH or O-(C1-C3)-alkyl in meta-position, or R4 and R5 form in common group 3,4-OCH=CH- or OCH=CHO-; R6 means (C1-C3)-alkyl, or salt-forming active substance represents a salt-forming compound among 6-dimethylaminomethyl-1-phenylcyclohexane compounds of the general formula (II) wherein R1' represents H, -OH, Cl or F; R2' and R3' have similar or different values and represent H, (C1-C4)-alkyl, benzyl, -CF3, -OH, -OCH2-C6H5, O-(C1-C4)-alkyl, Cl or F under condition that at least one among radicals R2' either R3' means H; R4' represents H, -CH3, -PO-(O-C1-C4-alkyl)2, -CO-(O-C1-C5-alkyl, -CO-NH-C6H4-(C1-C3)-alkyl, -CO-C6H4-R5', CO-(C1-C5)-alkyl), -CO-CHR6'-NHR7' or unsubstituted either substituted pyridyl, thienyl, thiazolyl or phenyl group; R5' represents -OC(O)-(C1-C3)-alkyl in ortho-position or -CH2N(R8')2 in meta- or para-position and wherein R8' means (C1-C4)-alkyl, or both radicals R8' in common with nitrogen atom (N) form 4-morpholino-group, and R6' and R7' have similar or different values and represent H or (C1-C6)-alkyl under condition that if both radicals R2' and R3' represent H then R4' doesn't mean -CH3 when R1' represents additionally H, -OH or Cl, either R4' doesn't mean H when R1' represents additionally -OH. Also, invention relates to a medicinal agent based on indicated salts.
EFFECT: valuable medicinal properties of salts and drug.
14 cl, 1 tbl, 8 ex
FIELD: organic chemistry, biochemistry, enzymes.
SUBSTANCE: invention relates to compounds represented by the formula: wherein values of substitutes are given in the invention description. Also, invention relates to pharmaceutically acceptable salts of the compound that can be used in treatment and/or prophylaxis of cathepsin-dependent states or diseases of mammals. Proposed compound are useful in treatment of diseases wherein bone resorption inhibition is desired, such as osteoporosis, increased mineral density of bone and reducing risk of fractures. Proposed claimed compounds are designated for preparing a drug possessing the inhibitory activity with respect to cathepsin.
EFFECT: valuable medicinal and biochemical properties of compounds.
24 cl, 13 sch, 4 tbl, 15 ex
SUBSTANCE: invention relates to aryl or heteroarylpiperazines with general formula II , where R2 is hydrogen or C1-4-alkyl (i) R1 is branched C4-6-alkyl, branched C4-6-alkenyl or branched C4-6-alkynyl, under the condition that R1 is not isobutyl, - C3-5-cycloalkyl, C3-7-cycloalkenyl, C3-6-cycloalkyl-C1-3-alkyl or C3-6-cycloalkenyl-C1-3-alkyl, -R1 and R2 together form a C3-6-alkylene bridge, and A is or or (ii) R1 - is ethyl, n-propyl or isopropyl, - R1 and R2 together form a C3-6-alkylene bridge, and A is or . Described also is a pharmaceutical composition based on formula II compounds, use of formula II compounds and method of treatment.
EFFECT: compounds exhibit high and selective bonding affinity to histamine H3 receptor and can be used for treating diseases and disorders, related to histamine H3 receptor.
49 cl, 149 ex
SUBSTANCE: invention relates to novel nonsteroid synthetic derivatives with the following structures or their pharmaceutically acceptable salts:
, , ,
, which are capable of modulating the androgen receptor.
EFFECT: invention relates to pharmaceutical compositions containing said derivatives and use thereof to make nonsteroid medicinal agents for treating and/or preventing conditions or diseases such as prostate hyperplasia, prostate cancer, hirsutism, severe hormone-dependant alopecia or acne etc, resulting from antagonistic activity towards the androgen receptor.
6 cl, 5 dwg, 3 tbl,12 ex
SUBSTANCE: invention relates to novel 3-substituted 4-(phenyl-N-alkyl)piperazine compounds of formula (1) , where R1 represents OSO2CF3, OSO2CH3, SO2R3, COCF3 and COCH2CH3, R2 represents C1-C4 alkyl or allyl, R3 represents C1-C3 alkyl or CF3, as well as to their pharmaceutically acceptable salts. The disclosed compounds are capable of modulating dopamine neurotransmission.
EFFECT: invention discloses pharmaceutical compositions of compounds which are used for treating disorders of the central nervous system.
4 cl, 24 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to medicine, namely new organic compounds, namely N,N'-substituted piperazines of general formula (I), wherein R1, R2: linear or branched alkoxy (C1÷C4), CH3C(=O)O; n=1-5; m=0-3; Z: C=O, SO2; X:C(=NH)NH2, C(=NH)NHC(-NH)NH2, G is low-molecular organic or mineral acid, sodium, potassium, ammonium cations or water influences the haemostasis system, showing antiagregant, anticoagulant and vasodilator properties, and to a method for preparing N,N'-substituted piperazines of formula 1 by reaction of N-substituted piperazines of general formula wherein R1, R2; linear or branched alkoxy (C1÷C4), CH3C(=O)O; n=1-5; m=0-3; Z: C=O, SO2; and 1H-pyrazole-1-carboxamidine, dicyane diamide and their salts in organic solvents or water at temperature 10-50°C in the presence of bases.
EFFECT: new substance are promising for prevention and treatment of the disturbed haemostasis system.
12 cl, 10 tbl, 14 ex