N-(2,4,6-trimethylphenylsulfonyl)-n-allylnormorphine bromide, showing anti-ischemic and anti-arrhythmic effect in ischemic heart disease and method thereof
(57) Abstract:A new chemical compound is N-(2,4,6-trimethylphenylsulfonyl)-N-allylnormorphine bromide formula 1 shows the experimental animals and in clinical conditions anti-ischemic and anti-arrhythmic effect in ischemic heart disease and can be used to create a promising drug for the treatment of coronary heart disease. A method of obtaining compound 1, which consists in the interaction of N-(2,4,6-trimethylphenylsulfonyl) research with methyl-allyl at a molar ratio of 1:1,4-1,6, respectively, in the environment of isopropyl alcohol at a temperature of 55-65oWith subsequent separation of the target product after cooling the reaction mass to room temperature. Yield 90%, the content of the basic substance is not less than 99%. 2 C. p. F.-ly, 9 PL. The invention relates to medicine, specifically to medicines used in the treatment of ischemic heart disease, and arrhythmias complicating her.The problem of prevention and treatment of coronary heart disease is very relevant, because the death of patients suffering from diseases of the cardiovascular system, occupies the first place in Loznitsa severe arrhythmia, in the treatment of this disease it is necessary to apply a combination of drugs with anti-ischemic and anti-arrhythmic effect, which does not always give a positive result.The aim of the invention is the creation of medicines for the treatment of ischemic heart disease and arrhythmias complicating her, and the development of a method of obtaining high output.This goal is achieved by N-(2,4,6-trimethylphenylsulfonyl)-N-allylnormorphine bromide of formula (1):
< / BR>The study of pharmacological activity 1.1. Anti-ischemic activity 1.The effect of 1 was studied on white nonlinear rats weighing 250-300 g by well-known methods, which allows to estimate the influence of the test substance on the sizes of the zones of ischemia and necrosis in the acute period of myocardial infarction. As the comparison drug used obzidan, anti-ischemic effect of which is known (Mashkovsky M. D. Medicines. M. Medicine, 1993, H. 1, S. 330-332).The results of these studies are presented in table.1.From the presented data it follows that 1 reduces the size of the zone of necrosis in relation to the area of ischemia and the effect of the preparation according to the influence of 1 on coronary blood flow was performed by well-known methods N. C. Kaverina on narcotized eleminal-sodium (50 mg/kg intraperitoneally) cats, translated into controlled breath. After opening the chest and kanalirovaniya coronary sinus blood flow out of it was sent to the jugular vein so that with the tee at the right period of time it was possible to carry out the sampling of venous blood from the coronary vessels in a measuring Cup. Each time the fence flowing blood continued for 15 C. the amounts Collected blood was multiplied by 4 and got the volumetric rate of flow for 1 min After introduction 1 the study of coronary blood flow produced in 5, 15, 30 and 60 minutesThe results are presented in table.2.The data show that 1 in a dose of 1 mg/kg and even more in the dose of 2 mg/kg increases the volumetric rate of coronary blood flow during the first 10 min of observation.3. Antiarrhythmic activity 1 in the acute phase of experimental myocardial infarction.Research carried out on mongrel dogs weighing 8-25 kg and cats weighing 2-4 kg Violation of coronary circulation caused anesthetized with geksenal (50 mg/kg intraperitoneally) animals by applying ligatures on the upper third of the descending branch of the left crown of choice for treatment of arrhythmias in the acute phase of myocardial infarction.The results of study 1 in cats is shown in table.3, the dogs table.4.The results are shown in table.3, show that 1 is superior to lidocaine for antiarrhythmic activity on the model of ventricular arrhythmia in cats caused by ligation of the coronary artery, and protivopellargnoe step 1 does not differ from the comparison drug.It is important to note that 1 not only prevents the onset of ventricular fibrillation and ventricular fibrillation, but it is able to remove an already existing arrhythmia. This is evidenced by the second series of experiments conducted with the drug that was introduced on the background of already existing arrhythmias (table.3,series 2).The same data obtained in the study of antiarrhythmic activity 1 in acute disorders of the coronary circulation in dogs (table.4). Intravenous administration of 1 after applying ligatures on coronary vessel can prevent the onset of arrhythmia in most animals during the 10 o'clockAntiarrhythmic effect of lidocaine at a dose of 15 mg/kg in the same experimental conditions is less than 30 minutes 1 also has a pronounced antiarrhythmic effect in later periods after nanosensornyh experimental conditions antiarrhythmic effect of lidocaine lasts 5-10 minutesThus, 1 has a pronounced antiarrhythmic activity in the cardiac arrhythmias resulting from myocardial ischemia. 1 differs from lidocaine higher activity and longer antiarrhythmic effect.An important feature of 1 is the combination of antiarrhythmic and antiischemic action, what makes this tool the drug of choice for treatment of arrhythmias in the acute phase of myocardial infarction.4. Antiarrhythmic activity 1 in patients with ischemic heart disease.Antiarrhythmic activity of 1 was investigated in the form of acute drug test. Evaluation of antiarrhythmic action 1 was produced using the apparatus of the Ribbon-MT, which allows dynamic electrocardiography with subsequent analysis of the recording. Background Holter ECG monitoring was performed in patients in whom there were no indications for emergency relief of arrhythmia, and if any type and class of arrhythmia was determined by means of kardiomonitorami for 30-120 min or recording ECG-12.In table. 6 shows comparative data antiarrhythmic actions 1 and lidocaine when arrhythmias complicating coronary artery disease.Intravenous administration of 1 caused a complete and stable suppression of ventricular arrhythmias in 39 patients with acute myocardial infarction and one patient had a significant (more than 50%) reduction in the incidence of ventricular arrhythmia. The other 42 patients with ischemic heart disease antiarrhythmic effect 1 was observed in 38 patients. These data indicate high antiarrhythmic activity 1 with ventricular arrhythmias ischemic Genesis.Lidocaine, which is antiaritmikom of choice for treatment of arrhythmias ischemic origin, especially in the acute phase of myocardial infarction, showed full antiarrhythmic effect in arrhythmias complicating acute myocardial infarction in 10 patients out of 17, which was significantly lower when compared with 1 (P < 0,05).In 73% of patients with CHD who had chest pain introduction 1 was accompanied by either a complete disappearance of pain, or a noticeable reduction.5. Antianginal activity (AAA) 1.Surveyed 11 men aged 30 to 60 years with angina II and III functional classes.To identify and objectification AAA 1 used the method of paired Bicycle exercise test (VEM). Cardamine second VEM intravenously was administered 1 dose of 1.5 mg/kg Loading was stopped when ST-segment depression of 1 mm or more at a distance of 0.08 to point j in combination with angina. Criterion AAA believed to increase the duration of the load on the background of the drug for at least 2 minutesIn 7 (64%) patients registered anti-ischemic effect 1. Although the remaining patients, 1 was ineffective on the adopted criteria, all of the observed increase in tolerance to physical activity: increase the time or power load and total work performed from 8 to 125% (average 40%).Nitrosorbid, which is the reference drug of these studies, the dose of 10 mg is not inferior to the severity of antianginal action 1. In only one case 1 was more effective nitrosorbid. It should be noted that two patients both drugs in the tested doses were ineffective.From these results, it follows that 1 has anti-ischemic effects, corresponds roughly to nitrosorbid.The presented results strongly suggest that 1 has anti-ischemic and antianginal activity. These effects are 1, found experimental and clinical confirmation, combined with a pronounced is the rhythm action 1 is shown, as in experiment and clinic in the acute phase of myocardial infarction.The combination of pharmacological properties listed 1 makes the product very promising to improve the pharmacotherapy of acute period of myocardial infarction.The method of obtaining 1 lies in the interaction of N-(2,4,6-trimethylphenylsulfonyl)research (II) with methyl-allyl (III) in isopropyl alcohol at a molar ratio of II:III 1:1,4-1,6, respectively, at a temperature of 55-65oC. Target product are filtering dropped 1 after cooling the reaction mass to room temperature. Get 1 in the form of almost white crystalline powder with a yield of 90% counting on II, so pl. 172-176oWith (in the range of two degrees). After recrystallization from isopropyl alcohol get Pharmacopoeia 1.The method according to the invention is illustrated by the following example.Example. Mix 400 ml of isopropyl alcohol, to 100.3 g of 99.7%, 100 g (0.38 mol) of 100% II and 50 ml (0.58 mol) III. The mixture is maintained at 55-65oC for 7 h, then cooled to room temperature. The precipitation 1 is filtered off, washed with isopropyl alcohol. Get 132,3 g 99,4% or 131, 5mm g 100% 1 that ascout Pharmacopoeia 1.The connection I easily soluble in water, insoluble in ether, chloroform.Found, N 7,6; Br 20,6.WITH18H27N2O2Br.Calculated, N 7,31; VG 20,84.The purity and identity of the products of the reaction is checked by thin-layer chromatography on plates "Silufol UV-254 in the solvent system chloroform ethanol 95% acetic acid, 95 4,5 0,5 with the manifestation of the camera to chlorine over a mixture of 3% solution of potassium permanganate 15% solution of hydrochloric acid. Plate after drying spray the solution on tolidine.The PMR spectrum is cleared on the device Hitachl Perkin elmer, the operating frequency of 90 MHz, internal standard hexamethyldisiloxane, the temperature of the 35oC. the Solvent is deuterated dimethylsulfoxide and acetone. Chemical shifts of protons (M. D. ) is shown on the scale . The signals of protons: 3,75-4,10 m D. M(CH2)48H of the research; to 4.52 M. D. (CH2) 2N allyl; 4,81 m D. C (CH2)-2N acetic acid; 5,56 5,91 m D. M(CH2)-2H allyl; 5,91 6,5 m D. M(SN)-1H allyl; for 6.81 M. D. (2H)- 3.5 N aromatics; 10,38 M. D. (NH).The following example parameters of the process of obtaining 1 was found experimentally and are optimal, as evidenced by the results is the atur reaction. The experiments showed that the optimum temperature range 55-65oC. At lower temperatures the reaction until the end comes, decreases the yield of the target product 1. At higher temperatures there is the resinification of the reaction mixture, the target material 1 is subjected to degradation with the formation of the original product II, the result is the target product 1, does not satisfy the requirements for color, extraneous impurities.As follows from the table.8, the optimum molar ratio of the reactants II:III if the reaction 1:1,4-1,6, respectively. Reducing the number III leads to a significant reduction of output, and the increase is unacceptable because of the deteriorating quality of the target product 1.As can be seen from the table.9, the optimal temperature selection connection 1 room temperature is 18-25oC. temperature Reduction does not lead to any significant increase in output, at elevated temperatures observed loss in output.In addition, in the process of obtaining 1 has been tested using other solvents. The yield of 1 was lower. than in the proposed method, and in some cases lower quality 1. 1. N-(2,4,6-Trimetazidine action in ischemic heart disease.2. The method of obtaining N-(2,4,6-trimethylphenylsulfonyl)-N-allylnormorphine bromide of the formula I, wherein N-(2,4,6-trimethylphenylsulfonyl)morpholine is subjected to interaction with methyl-allyl environment of isopropyl alcohol at a molar ratio of N-(2,4,6-trimetilfenil carbamoylmethyl)the research and allyl bromide 1 1,4 1,6 respectively, and a temperature of 55 to 65oC, followed by cooling the reaction mixture to room temperature and excretion of N-(2,4,6-trimethylphenylsulfonyl)-N-allylnormorphine bromide.
where R1group cyclic amide, such as 2H-3,4-dihydro-1,3-benzoxazin-2-she, 2H-3,4-dihydro-1,3-benzoxazin-2,4-dione, and 1,2,3,4-tetrahydroquinazoline-2,4-dione, and 1,2,3,4-tetrahydroquinazolin-2-it, 1,2,3,4-tetrahydropyrido(3,2-d)-pyrimidine-2,4 - dione, and 1,2,3,4-tetrahydropyrido(3,2-d)pyrimidine-2-it, 1,2,3,4-tetrahydropyrimidine-2,4-dione, pyrrolidin-2-it, 1,2,3,4 - tetrahydropyridine-2-it, 5H-6,7,8,9-tetrahydropyrido(3,2-b)azepin-6-she N-5,6,7,8-tetrahydropyrido(2,3-b)azepin - 8-she, 2H-3,4-dihydropyrido(2,3-e)-1, 3-oxazin-2-thione or 2-she pyrrolidine (3,4-b)-pyrazin-5-she 1H-2,3,4,5-tetrahydrothieno(2,3-b)indol-2-it, 8H-4,5,6,7-tetrahydrothieno(2,3-b)thiophene-7-she 4H-pyrazolo(5,4-f)benzazepin-9-it, isoindoline-1,3-dione, benzoxazolyl-2-it, unsubstituted or substituted lower alkyl, lower alkoxy, halogen, the nitro-group, carboxy, benzoyl or benzyl, n is zero or an integer from 1 to 6, Z is a group of formula (A) or (B):
N-(CH2)mR2(A) or -(CH2)p, dioxolane, furan, tetrahydrofuran, methylfuran or thiophene, m is an integer from 1 to 3; R3is lower alkyl; R4is phenyl or a radical of dioxolane, furan or thiophene, p = 1, provided that when R1radical 1,2,3,4-tetrahydrobenzo-2-or 1,2,3,4-tetrahydroquinazoline-2,4-dione, R2and R4are not phenyl or substituted by a halogen phenyl, or their pharmacologically acceptable salts with antiacetylcholinesterase activity
FIELD: organic chemistry, chemical technology, medicine, biochemistry, pharmacy.
SUBSTANCE: invention relates to new derivatives of sulfonamides of the formula (I) or their pharmaceutically acceptable salts wherein R1 means -OH or -NHOH; R2 means hydrogen atom; R3 means alkyl, alkoxyalkyl, arylalkyl, pyridylalkyl or morpholinylalkyl; A means piperidyl or tetrahydrofuranyl; n = 0; E means a covalent bond; (C1-C4)-alkylene, -C(=O)-, -C(=O)O- or -SO2-; X means hydrogen atom, alkyl, aryl, arylalkyl, alkoxyalkyl, morpholinyl or tetrahydropyranyl; each among G and G' means -C(R5)=C(R5') wherein R5 and R5' mean hydrogen atom; M means the group -CH-; z means the group -(CR7R7')a-L-R8 wherein a = 0 and each among R7 and R7' means hydrogen atom; L means a covalent bond; R8 means halogen atom or alkoxy-group. Compounds of the formula (I) are inhibitors of metalloproteases and can be used for treatment of arthritis, cancer tumors and other diseases.
EFFECT: valuable medicinal properties of compounds.
15 cl, 7 tbl, 56 ex
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, medicine, pharmacy.
SUBSTANCE: invention describes 2-phenyl-substituted imidazotriazinones of the general formula (I): wherein R1 and R2 mean independently linear (C1-C4)-alkyl; R3 and R4 are similar or distinct and represent hydrogen atom or linear or branched (C1-C4)-alkenyl or (C1-C4)-alkoxy-group, linear or branched (C1-C6)-alkyl chain that can be broken by oxygen atom, and/or it can comprise from to some similar or different the following substitutes: methoxy-, hydroxy-, carboxyl, linear or branched (C1-C4)-alkoxycarbonyl, and/or residues of formulae -SO3H, -(A)a-NR7R8, -O-CO-NR7'R8', and/or wherein A means a number 0 or 1; A means residue -CO or -SO2; R7 and R8 mean hydrogen atom (H), cyclopentyl, cyclohexyl, cycloheptyl, phenyl, piperidinyl or pyridyl that can be substituted with different substitutes, methoxy-, (C1-C6)-alkyl and others; R7' and R8' mean (C1-C6)-alkyl. Also, other values of radicals R3 and R4 are given, a method for their preparing and a pharmaceutical composition. Described compounds are inhibitors of phosphodiesterases and can be used in manufacturing agents showing an anti-thrombosis, anti-proliferative, anti-vasospastic and vasodilating effect.
EFFECT: improved preparing method, valuable biochemical and medicinal properties.
10 cl, 6 tbl, 337 ex
FIELD: organic chemistry, chemical technology, biochemistry, medicine, pharmacy.
SUBSTANCE: invention relates to new derivatives of propene carboxylic acid amidooximes of the formula (I):
wherein R means phenyl that is substituted optionally with 1-3 substitutes wherein substitute means (C1-C2)-alkyl or (C1-C2)-alkoxy-group; R' means hydrogen atom (H); R4 and R5 mean independently of one another H, (C1-C5)-alkyl, phenyl that is substituted optionally with 1-3 substitutes wherein substitute means (C1-C2)-alkyl or (C1-C2)-alkoxy-group; or R4 and R5 in common with adjacent nitrogen atom form 5- or 6-membered saturated or unsaturated heterocyclic group that can comprise additional nitrogen atom or oxygen atom as a heteroatom and it can be condensed with benzene ring, and heterocyclic group and/or benzene ring can comprise one or two substitutes wherein substitute means (C1-C2)-alkyl or (C1-C2)-alkoxy-group; R1 and R2 mean H; R3 means H, OH; or R1 in common with R2 forms carbonyl group wherein carbon atom is joined with oxygen atom adjacent with R1 and with nitrogen atom adjacent with R2; R3 means H, OH; or R2 means H; and R1 in common with R3 form a valence bond between oxygen atom adjacent with R1 and carbon atom adjacent with R3; and its geometric isomers and/or optical isomers, and/or its pharmaceutically acceptable acid-additive salts. Compounds of the formula (I) inhibit activity of poly(adenisone diphosphate ribose) polymerase and can be used in pharmaceutical composition in treatment of states based on inhibition of this enzyme activity, and in treatment of states associated with oxygen insufficiency of heart and brain. Also, invention describes methods for preparing compounds of the formula (I).
EFFECT: improved preparing method, valuable medicinal properties of compounds and compositions.
9 cl, 1 tbl, 41 ex
FIELD: medicine, pharmacology.
SUBSTANCE: the present innovation deals with applying pharmaceutical composition as an antagonist of NPY Y5 receptor that contains the compound of formula I
, moreover, it deals with compounds of formula I and method for treating obesity and suppressing food intake, as well.
EFFECT: higher efficiency of therapy.
18 cl, 13 ex, 6 tbl
FIELD: organic chemistry, chemical technology, medicine, pharmacy.
SUBSTANCE: invention relates to compounds of the formula (I)
or their pharmaceutically acceptable salts or esters hydrolyzing in vivo and possessing activity inhibiting the cellular cycle and selective with respect to CDK-2, CDK-4 and CDK-6. Compounds can be used in cancer treatment. In the formula (I) R1 represents halogen atom, amino-group, (C1-C)-alkyl, (C1-C6)-alkoxy-group; p = 0-4 wherein values R1 can be similar or different; R2 represents sulfamoyl or group Ra-Rb-; q = 0-2 wherein values R2 can be similar or different and wherein p + q = 0-5; R3 represents halogen atom or cyano-group; n = 0-2 wherein values R3 can be similar or different; R4 represents hydrogen atom, (C1-C6)-alkyl, (C2-C6)-alkenyl, (C2-C6)-alkynyl, (C3-C8)-cycloalkyl, phenyl or heterocyclic group bound with carbon atom wherein R4 can be optionally substituted at carbon atom with one or some groups Rd; R5 and R6 are chosen independently from hydrogen, halogen atom, (C1-C)-alkyl, (C2-C6)-alkenyl or (C3-C8)-cycloalkyl wherein R5 and R6 can be substituted at carbon atom independently of one another with one or some groups Re; Ra is chosen from (C1-C6)-alkyl, (C2-C6)-alkenyl, (C2-C6)-alkynyl, (C3-C8)-cycloalkyl, (C3-C8)-cycloalkyl-(C1-C6)-alkyl, phenyl, heterocyclic group, phenyl-(C1-C)-alkyl or (heterocyclic group)-(C1-C6)-alkyl wherein Ra can be substituted optionally at carbon atom with one or some groups Rg and wherein if indicated heterocyclic group comprises residue -NH- then its nitrogen atom can be optionally substituted with group chosen from the group Rh; Rb represents -N(Rm)C(O)-, -C(O)N(Rm)-, -S(O)r-, -OC(O)N(Rm)SO2-, -SO2N(Rm)- or -N(Rm)SO2- wherein Rm represents hydrogen atom or (C1-C6)-alkyl, and r = 1-2. Also, invention relates to methods for synthesis of these compounds, a pharmaceutical composition, method for inhibition and using these compounds.
EFFECT: improved preparing method, valuable medicinal properties of compounds and pharmaceutical compositions.
24 cl, 3 sch, 166 ex
SUBSTANCE: the present innovation deals with surgical, antiseptic, antiphlogistic and wound-healing glue that contains collagen hydrolyzate, sodium salt of alginic acid, catapol, dioxidin, poviargol; additionally, it contains glycerol, nipagin, nipasol and aqueous solution of sodium hypochlorite. The innovation provides increased antimicrobial activity and regulation of biodegradation rate of covering depending upon the level of inflammatory process in the wound that leads to faster wound healing.
EFFECT: higher efficiency of application.
FIELD: organic chemistry, medicine, pharmacy.
SUBSTANCE: invention proposes using the compound (R/S)-(-/+)-2-[5-(4-fluorophenyl)-3-pyridylmethylaminomethyl]-chroman or (S)-(+)-2-[5-(4-fluorophenyl)-3-pyridylmethylaminomethyl]-chroman or their salts for preparing a medicinal agent. This agent is used in treatment of extrapyramidal motor disorders, in particular, in treatment of unfavorable effects of anti-parkinsonic preparations and using (S)-(+)-2-[5-(4-fluorophenyl)-3-pyridylmethylaminomethyl]-chroman in combination with an anti-parkinsonic preparation for preparing the combined medicinal agent. Also, invention relates to a pharmaceutical composition for treatment of extrapyramidal disorders and a set of the same designation. Proposed compounds are able to prevent catalepsy caused by usual anti-dopaminergic preparations and they are strong agonists of 5-HT1A-receptors in combination with antagonism to dopamine D2-receptors and interaction with D3-receptors that provides positive effects on extrapyramidal system in treatment of dyskinesia.
EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.
26 cl, 10 ex
FIELD: organic chemistry, medicine, pharmacy.
SUBSTANCE: invention relates to cyclopentyl compounds of the general formula (I): wherein X means carbon (C), nitrogen (N) or oxygen (O) atom; Y means O; Z means C; R1 means hydrogen atom, -(C0-C6)-alkyl-W-(C1-C6)-alkyl-, -(C0-C6)-alkyl-W-(C0-C6)-alkyl-(C3-C7)-cycloalkyl-(C0-C6)-alkyl wherein alkyl and cycloalkyl are optionally substituted with 1-7 independent substitutes chosen from hydroxy-group, -O-(C1-C3)-alkyl, trifluoromethyl, (C1-C3)-alkyl; W means a simple bond, -O-, -CO-, -CO2-, -CONR10- or -NR9-; R2 means -(C0-C6)-alkyl, (C0-C6)-alkyl-W-(C1-C6)-alkyl or (C0-C6)-alkyl-W-(C3-C7)-cycloalkyl wherein (C1-C6)-alkyl, (C3-C7)-cycloalkyl are optionally substituted with 1-6 substitutes chosen from halogen atom, trifluoromethyl, -(C1-C6)-alkyl; R3 means hydrogen atom, -(C0-C6)-alkyl-phenyl, -(C0-C6)-alkyl-heterocycle, -(C0-C6)-alkyl-(C3-C7)-cycloalkyl, -(C0-C6)-alkyl-CO2R10, -(C0-C6)-alkyl-(alkene)-CO2R10, -(C0-C6)-alkyl-SO3H, -(C0-C6)-alkyl-W-(C0-C4)-alkyl, -CONR10N10- or -NR10CO2R10-, -NR10-(C0-C3)-alkyl-CO2R10- wherein phenyl and heterocycle, cycloalkyl or (C0-C6)-alkyl are optionally substituted with 1-5 independent substitutes chosen from halogen atom, trifluoromethyl, hydroxy-group, (C1-C3)-alkyl, -O-(C0-C3)-CO2R10, -CN, =O, -NR10R10, -CONR10R10, -SO3-R10 or -(C0-C3)-alkyl-heterocycle and wherein phenyl can be condensed with heterocycle that the latter can be substituted with 1-2 hydroxyl groups; R4 is absent if X represents O or N, or if a double bond joints carbon atoms to which R3 and R6 are added, or R4 means hydroxy-group, -(C0-C6)-alkyl, -CN, -(C0-C3)-CO2R10; or R3 and R4 are combined and form 1H-indenyl, 2,3-dihydro-1H-indenyl, cyclopentanyl or cyclohexanyl ring wherein this obtained cycle is optionally substituted with 1-5 substitutes chosen independently from hydroxy-group, (C1-C3)-alkyl, -O-(C1-C3)-alkyl and -(C0-C3)-CO2R10; or R3 and R5, or R4 and R6 are combined and form phenyl or heterocyclic ring wherein this ring is optionally substituted with 1-7 independent substitutes chosen from hydroxy-group, (C1-C3)-alkyl, -O-(C1-C3)-alkyl, -CO2R10; R5 and R6 mean independently hydrogen atom, hydroxy-group, (C1-C6)-alkyl or (C0-C6)-alkyl-CO2R10; if Z means C then R7 means hydrogen atom, (C1-C6)-alkyl; R8 means hydrogen atom; R10 means hydrogen atom, -(C1-C6)-alkyl, benzyl, phenyl or -(C0-C6)-alkyl-(C3-C6)-cycloalkyl; n1 and n2 = 0, 1 or 2 independently and the sum n1 + n2 = 0, 1, 2 or 3; a dotted line represents a simple or double bond, and other
compounds of this series. Also, invention relates to a pharmaceutical composition modulating activity of chemokine receptors, a method for modulation of activity of chemokine receptors in mammals, and to a method for treatment, improving, regulating or decreasing risk of inflammatory and immunoregulatory disorder or disease. Invention provides synthesis of novel compounds possessing valuable biological properties.
EFFECT: valuable medicinal and biological properties of compounds and pharmaceutical composition.
21 cl, 4 tbl, 81 ex
FIELD: organic chemistry, medicine, pharmacy.
SUBSTANCE: invention relates to novel compounds of the formula (IA) or (IB) given in the invention description wherein R1 means hydrogen atom, (C1-C7)-alkyl, -(CH2)n-OH, -(CH2)n-N(R6)2; R2 means (C1-C7)-alkyl, -(CH2)n-N(R6)2, -NR6C(O)C(O)O-(C1-C7)-alkyl, -NR6-(CH2)n-OH, -NR6C(O)-(C1-C7)-alkyl, -NH-benzyl; R3 means hydrogen atom or amine; or R2 and R3 in common with carbon atoms to which they are bound mean the group -N(R6)-CH2-O-CH2-; R4 means hydrogen atom or (C1-C7)-alkyl; R5 means hydrogen atom; R6 means independently of one another hydrogen atom or (C1-C7)-alkyl; R' means hydrogen atom or (C1-C7)-alkyl; n = 0, 1, 2 or 3. Also, invention relates to a medicinal agent possessing the selective blocking activity with respect of subspecies of NMDA-receptors and containing one or more compounds of the formula (IA) or (IB) or their pharmaceutically acceptable acid-additive salt or inert carrier. Invention provides preparing novel compounds possessing the high affinity to NMDA-receptors that can be used as components of a medicinal agent for treatment of diseases mediated by these receptors.
EFFECT: valuable medicinal properties of compounds and drug.
13 cl, 35 ex
FIELD: organic chemistry, chemical technology, medicine, pharmacy.
SUBSTANCE: invention relates to a new biologically active compound. Invention describes quaternary ammonium derivative of lidocaine of the formula:
eliciting anti-arrhythmic activity. Also, invention describes a method for preparing quaternary ammonium derivative of lidocaine of the formula (1). Method involves interaction of N-(2,6-dimethylphenylaminocarbonylmethyl)-morpholine with allyl bromide in isopropyl alcohol medium at temperature 58-62°C followed by cooling the reaction mixture to room temperature and isolation of N-allyl-(2,6-dimethylphenylaminocarbonylmethyl)-morpholinium bromide. Invention provides preparing new compound eliciting useful biological properties.
EFFECT: improved preparing method.
2 cl, 4 tbl, 4 ex
FIELD: chemistry of metalloorganic compounds, agriculture.
SUBSTANCE: invention describes derivatives of mepiquate borate of the general formula (I): wherein DMP means N,N-dimethylpiperidinium (mepiquate); M means metal cation acceptable for agriculture and chosen from a series comprising sodium, potassium, magnesium, calcium, zinc, manganese or copper, hydrogen atom or NH4 +; O means oxygen atom; A means chelate of complex-forming fragment bound with one boron atom and representing (lower)-alkylglycols or sugars; n and m mean similar whole numbers in the range from 1 to 6; x means a whole or fraction number in the range from 0 to 10; y means a whole or fraction number in the range from 1 to 48; z means a whole or fraction number in the range from 0 to 48; v means a whole or fraction number in the range from 0 to 24, and w means a whole or fraction number in the range from 0 to 24. Also, invention describes methods for preparing compound of the formula (I) by interaction of N,N-dimethylpiperidinium hydroxide with boric acid and/or boron-containing oxides and optionally with metal hydroxides acceptable for agriculture indicated above or electrochemical method involving interaction of N,N-dimethylpiperidinium halide in the presence of water and boric acid and in the presence metal hydroxides acceptable for agriculture by bipolar electrodialysis. Invention describes electrochemical method for preparing N,N-dimethylpiperidinium hydroxide and a suspension concentrate possessing the plant growth-regulating effect prepared by mixing N,N-dimethylpiperidinium hydroxide, boron-containing compound chosen from boric acid and borate salt with a thickening agent and water, or by mixing compound of the formula (I) with Na2B8O13 x 4 H2O, a thickening agent and water. Prepared derivatives of mepiquate borate possess the improved indices of hygroscopicity and corrosion activity.
EFFECT: improved preparing methods, valuable properties of derivatives.
22 cl, 7 tbl, 16 ex