3-(2'-naphthylmethyl)-piperazine-2 and 1-n-phenyl-3 - ventilationperfusion-2, exhibiting anti-inflammatory activity
(57) Abstract:3-(21-Naphthylmethyl)-piperazine-2 (1) and 1-N-phenyl-3-piperazino-2 (II) formula
< / BR>where I R = 2-naphthyl; R1= N;
II R = C6H5; R1= C6H5.can be used in medicine as anti-inflammatory agents. They get interaction arilpirolilor acids with Ethylenediamine and N-phenylethylenediamine, respectively, when heated in ethanol medium in the presence of catalytic amounts of acetic acid according to the scheme
< / BR>where I R = 2-naphthyl; R1= H;
II R = C6H5; R1= C6H5.I. The Output Is 78.4%. Tpl.241-242oC.Found, %: C 72,32; N. Of 5.17; N 10,56%; C16H14N2O2.Calculated,%: C 72,17; H Of 5.29; N 10,52.II. Yield 68%. Tpl.140-141oC.Found, %: C 73,80; N. Of 5.39; N 9,72; C18H16N2O2.Calculated, %: C 73,95; N 5,52; N 9,58.The compounds possess anti-inflammatory activity of 45% (I) and 51% (II). Toxicity LD50is more than 1000 mg/kg 1 tab. The invention relates to new biologically active compounds 2-piperazinone, namely 3-(2
II R C6H5; RIC6H5.possessing anti-inflammatory activity, suggesting the possibility of their use in medicine as anti-inflammatory drugs.The closest analogue to the structure with anti-inflammatory activity is 3-(4I-methylbenzylidene)-piperazine-2 formula:
< / BR>which is used as a prototype [1,2]
The objective of the invention, the search range 2-piperazinone compounds with pronounced anti-inflammatory activity with low toxicity.This is achieved by the synthesis of 3-(2I-naphthylmethyl)- and 1-N-phenyl-3-ventilationperfusion-2-ions containing 3-substituted and 1,3-substituted 2-piperazinone cycle, which has anti-inflammatory action.The claimed compounds produced by interaction arilpirolilor acids with Ethylenediamine and N-phenylethylenediamine, respectively, when heated in ethanol medium in the presence of catalytic amounts of acetic acid and subsequent separation of the target products by the known methods.The reaction scheme:
< / BR>where I R 2-naphthyl; R1H;
II R C6H5; RIC6H5.
oC.Found, C 72,32; N. OF 5.17; N 10,56; C16H14N2O2.Calculated C 72,17; N. Of 5.29; N 10,52.IR spectrum (VR-20) vaseline oil, cm-1: 3200, 3112 (amino group); 1692 (amide carbonyl); 1608 (-carbonyl).PMR spectrum (OC-2310, DMCO, GMDS, M. D.): 3,53 (int. m, 4H, CH2- CH2); 6,91 (C. 1H, CH); 8,08 (m N10H7); 8,77 (C. 1H, NH); 11,05 (C. 1H, NH).Compound II get the same way.Yield 1.98 g (68%), so pl. 140 -141oC.Found, C 73,80; N. OF 5.39; N 9,72; C18H16N2O2.Calculated C 73,95; N 5,52; N 9,58.IR-spectrum (UR-20) vaseline oil, cm-1: 3376 (amino group); 1692 (amide carbonyl); 1616 (g-carbonyl).PMR-spectrum (OC-2310, DMSO, GMDS, M. D.): 3,88 (int. m, 4H, CH2CH2); 6,77 (C. 1H, CH); to 7.67 (m, 10H, 2C6H5); 11,12 (C. 1H, NH).The claimed compounds are yellow crystalline substance, easily soluble in DMSO and DMF, soluble in hot ethanol, benzene, sparingly soluble in water.The compounds of bilene in oral introduction of the investigated compounds at a dose of 50 mg/kg, ortofena in the dose of 10 mg/kg 
About anti-inflammatory activity was judged by the degree of inhibition of the inflammatory response in Aggregate ED50and LD50was carried out according to the method of Litchfield and Wilcoxon signed 
The results of studies anti-inflammatory activity are presented in the table.From the table it is seen that the claimed compounds possess anti-inflammatory action, toxicity several times less toxic than used in medicine, the drug may also fuse 
Acute toxicity of the claimed compounds was determined in oral introduction connections to white mice. 2% starch mucus, N. Pershin  LD50the claimed compounds is more than 1000 mg/kgThus, 3-(2I-naphthylmethyl)-piperazine-2 - and 1-N-phenyl-3-ventilationperfusion-2, as shown by experimental studies, have a pronounced anti-inflammatory action. The toxicity of the compounds of more than 1000 mg/kg, equivalent to more than 1000 mg/kg and ortofena 380 mg/kg 3-(21-Naphthylmethyl)-piperazine-2 (I) and 1-N-phenyl-3-ventilationperfusion-2 (II) formula
< / BR>where I R=2-naphthyl, R'=H;
II R=C6H5; R'=C6H5,
< / BR>(I) possessing neuroleptic activity, and 3-methyl-N-[2-(4-phenylpiperazine)ethyl] benzamide as starting compounds in the synthesis of hydrochloride of 3-methyl-N-[2-(4-phenylpiperazine)ethyl]benzo - Mead
(I) where R is hydrogen, halogen, lower alkyl or lower alkoxygroup;
And group O or S;
In group-CH2-CH2or СНR1where R1means hydrogen, lower alkyl or hydroxyl;
X is oxygen or the group NH
The Y group of the formula)qwhere R2means lower alkyl, q is 2 or 3, and their salts, in particular physiologically tolerable salts, which possess pharmacological activity, in particular activity antimuskarinovoe act occurs, and therefore can be used to treat diseases of the gastrointestinal tract and respiratory tract
(I) or pharmaceutically acceptable salt accession acids him or stereoisomeric form of the compound, where
-A1= AND2- A3= AND4- bivalent radical having the formula
-CH=CH-CH=N (a-5) or
n=1 or 2
IN - NR4or CH2< / BR>R4is hydrogen or C1-C6alkyl
L is hydrogen, C1-C6alkyl, C1-C6allyloxycarbonyl, or a radical of the formula
-Alk - R5(b-1),
-Alk - Y - R6(b - 2),
-Alk - Z1- C(=X) - Z2- R7(b-3), or
-CH2- SNON - CH2- O - R8(b-4), where R5is cyano, phenyl optionally substituted C1-C6alkyloxy; pyridinyl; 4,5-dihydro-5-oxo-1-N-tetrazolyl; 2-oxo-3-oxazolidinyl; 2,3-dihydro-2-oxo-1-N-benzimidazolyl; or bicycling radical of formula (C-4-a)
Gwhere G2- CH=CH-CH=CH-, -S-(CH2)3,- -S-(CH2)/2-, -S-CH=CH - or-CH=C(CH3)-O-;
R6- C1-C6-alkyl, pyridinyl optionally substituted by nitro; pyrimidinyl; feast R7- C1-C6-alkyl; halophenol; 1-methyl-1H-pyrrolyl; furanyl, thienyl, or aminopyrazine;
Y is O or NH;
Z1or Z2each independently NH or a direct link X-O
each Аlk independently - C1-C6alcander
NNAlK where Alk is methyl or ethyl, with improved anthelminthic activity
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: medicine, oncohematology.
SUBSTANCE: the present innovation deals with treating elderly patients with chronic lympholeukosis accompanied with cardiovascular failure. The method deals with applying chemopreparations and cytoprotector. Moreover, 1 wk before the onset of chemotherapeutic therapy one should prescribe preductal at the dosage of 105 mg daily. At this background one should sample blood out of elbow vein at the volume of 200 ml into a vial with glugicir to centrifuge it, isolate plasma, divide into two portions, add into the 1st vial - cyclophosphan 600-800 mg/sq. m, vincristin 1.4 mg/sq. m, into the 2nd vial - adriamycin 50 mg/sq. m to be incubated for 30 min at 37 C and intravenously injected by drops for patients. Simultaneously, the intake of prednisolone should be prescribed at the dosage of 60 mg/sq. m since the 1st d and during the next 5 d and preductal at the dosage of 105 mg daily during a week, and then 2 wk more at the dosage of 60 mg daily. All the procedures should be repeated in above-mentioned sequence 4-6 times. The method enables to decrease toxic manifestations of chemotherapy while applying adequate dosages of cytostatics, anthracycline antibiotics, among them, at no great manifestations of their toxicity due to preductal's cardioprotective action.
EFFECT: higher efficiency of therapy.
1 ex, 5 tbl
FIELD: medicine, cardiology.
SUBSTANCE: it is suggested to apply cortisol antagonists in addition to clonidine while manufacturing preparation to treat heart failure. Moreover, one should introduce cortisol antagonist or a product that includes cortisol antagonist along with the second medicinal preparation being a combined preparation to be applied either simultaneously, separately or successively. The present innovation provides decreased symptoms of heart failure at decreasing cardiac muscle's fibrosis and heart sizes due to preferable impact upon glucocorticoid receptors in patient's heart and/or kidneys.
EFFECT: higher efficiency of application.
12 cl, 2 ex
SUBSTANCE: the present innovation deals with medicinal preparations designed as solution and indicated for therapeutic needs. Eye drops contain ciprofloxacin hydrochloride monohydrate being equivalent to 0.3% free foundation, a buffer system that keeps pH within 3.5-5.5 interval, as a conserving agent - benzalconium chloride and a s a stabilizer - the salt of disodium ethylenediamine tetraacetic acid, moreover, their range of osmolality values correspond to 150-450 mM/kg H2O. Eye drops should be obtained by preparing buffer system in which mannitol should be dissolved followed by the salt of disodium ethylenediamine tetraacetic acid, benzalconium chloride, ciprofloxacin hydrochloride. Then one should perform the control for the quality of obtained solution to be then filtered by applying sterilizing elements and packed. This innovation provides treatment of eyes at creating the pressure in an eye and at certain desired osmolality.
EFFECT: higher efficiency of therapy.
4 cl, 1 ex
SUBSTANCE: invention relates to endoparasitic agent containing cyclic depsipeptide of general formula 1 and piperazine of formula 2 .
EFFECT: endoparasitic agent with synergetic agent.
6 cl, 7 ex, 7 tbl
FIELD: medicine, oncology.
SUBSTANCE: the present innovation deals with treating oncological diseases. It is suggested to apply bisdioxopiperazine (previously known as cardioprotector) to either treat or prevent tissue lesions caused due to sporadic transudation of cytotoxic poison for topoisomerase II (represented by anthracyclines, etoposide, teniposide, mitoxantrone daunorubicin, doxorubicin, etc.), medicinal remedies and pharmaceutical set of the same indication. It is, also, suggested to apply the method to treat or prevent tissue lesions caused by sporadic transudation of topoisomerase II poison. BisdioxopiperazineICRF-187 has impact due to catalytic inhibiting topo II. Signs for possible transudation of topoisomerase II poison (of local toxicity) usually include the availability of acute pain, erythema, development of ulcerations in area of transudation; due to the action of ICRF-187 the quantity of wounds is reduced, or the development of side effects is not observed.
EFFECT: higher efficiency of therapy.
59 cl, 12 dwg, 13 ex, 10 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
SUBSTANCE: at performing curative endoscopy one should apply pneumoapplication of granulated sorbent - diovine at the quantity of 0.2 g, the pressure being 15 atm. at the distance of 1.5 cm against the defect onto the surface of bleeding rupture of gastric mucosa. Diovine's coarse-grained structure enables to keep the integrity of mucous-bicarbonate barrier due to providing normal vapor exchange and moisture medium in the defect. Moreover, diovine's antimicrobial action helps to suppress gram-positive and gram-negative microflora that enables to shorten terms for defects healing and decrease the frequency of repeated hemorrhages.
EFFECT: higher efficiency of therapy.
FIELD: medicine, pharmacy.
SUBSTANCE: invention proposes a medicinal formulation consisting of a core and the stomach-dissolving envelope. The core comprises trimetazidine dihydrochloride as an active component, and starch, mannitol, povidone, magnesium stearate, croscarmelose and microcrystalline cellulose as accessory substances. The envelope comprises hydroxypropylmethylcellulose, polyethylene glycol, titanium dioxide, magnesium stearate and acid red as a dye. Also, invention describes a method for making the trimetazidine medicinal formulation. Trimetazidine tablets show high mechanical strength in the low pressing strength (3.5-5 kH). The composition of the medicinal formulation provides releasing 80% of trimetazidine for 30 min.
EFFECT: improved and valuable properties of formulation.
3 cl, 1 tbl, 1 ex
FIELD: medicine, neurology, pharmacy.
SUBSTANCE: invention proposes using levetiracetam and the corresponding levetiracetam-base pharmaceutical composition used in treatment of bipolar disorders, mania and migraine. Also, invention relates to a pharmaceutical composition based on levetiracetam and at least one inhibitor of GABA type A neuronal receptors that is used in treatment of epilepsy, alcohol withdrawal syndrome, tremor, bipolar disorders, obsessive-compulsive disorder, panic state, depression, headache, pain, ischemia and head trauma, to corresponding methods for treatment, to a method for selective enhancing the therapeutic effect of inhibitors of GABA type A neuronal receptors, to a method for treatment of patient with inhibitor of GABA type A neuronal receptors involving the combined administration of indicated inhibitor of GABA type A neuronal receptors with levetiracetam. Invention shows the possibility for using levetiracetam for treatment of chronic and neuropathic pain in lower doses as compared with doses causing secondary effects, and shows its property to enhance activity of inhibitor of GABA type A neuronal receptors.
EFFECT: improved and valuable medicinal properties of agent.
18 cl, 18 tbl, 7 ex