The dihydrochloride of 1-diethylaminopropyl-2-phenylimidazo[1,2-a] benzimidazole with a local anesthetic action

 

(57) Abstract:

The dihydrochloride of 1-diethylaminopropyl-2-phenylimidazo-[1,2-a] benzimidazole of formula I has mestnoanesteziruushim action in terminal, wiring and spinal anaesthesia. table 2.

The invention relates to a new derivative 1H-imidazo[1,2-a]benzimidazole, namely water-soluble dihydrochloride 1-diethylaminopropyl-2-phenylimidazo[1,2-a]benzimidazole of the formula I

< / BR>
with mestnoanesteziruushim effect when the terminal wires or spinal anesthesia.

Mestnoanesteziruyuschie funds depending on the indication for use is classified according to the N. N. Karkishchenko (Pharmacological basis of therapeutics (a guide for physicians and students). GMR-M, Medicine, 1996, 559 (C) with some modifications as follows:

1. The tools used for surface anesthesia: cocaine, tetracaine, leakin, benzocaine, piromekain.

2. Drugs used mainly for infiltration and block anesthesia: novocaine, trimekain, lidocaine, rihlokain.

3. Drugs used for spinal and epidural anesthesia: Savkin, marcain.

4. Residuum action and found practical application in terminal anesthesia, was cocaine. However, due to the high toxicity of this drug has limited application (M. D. Mashkovsky. Medicines, 15th ed., Rev. and more. - M.: Medicine, 1998, H. 1, S. 371 - 382).

Subsequently widely used is less toxic anesthetic - novocaine, which is mainly used for infiltration and block anesthesia and not used for surface anesthesia (L. A. Melekhov, S. E. Mitin. Procaine blockade of the round ligament of the liver in the treatment of some diseases of abdominal cavity organs. Vestn. hir. them. I. I. Grekova, 1988, I. 141, No. 10, S. 134; M. D. Mashkovsky, 1998).

Widely known anesthetic for terminal anesthesia - tetrakis (dikain), which has analgesic activity in 2 - 3 times that of cocaine and 10 - 12 times novocaine, however, like cocaine has a high toxicity (M. D. Mashkovsky, 1998). In addition, side effects (tachycardia, convulsions, loss of consciousness, paralysis of the respiratory center), called (B. M. beavers. Our experience of applying the solution trimekainom for surface anaesthesia for ENT surgery. The honey.sister, 1990, N 9, p. 14 - 17), hinder its widespread use (O. F. Konovaltsev, N. P. Field. The action of aqueous solutions of dick is theanesthesiology means a new generation was lidocaine, which finds wide application in infiltration, conduction, spinal and sometimes terminal methods of pain relief (A. I. Levchenkov, A. L. Kostyuchenko, E. T. Rostomashvili and other Caudal epidural anesthesia during operations on the lower extremities in traumatology and orthopedics. Anestesiol. and Reanimator., 1992, No. 5 - 6, S. 15 - 17; M. D. Mashkovsky, 1998).

Lidocaine is usually well tolerated, but may sometimes cause the collapse, anaphylactic reaction, changes in the contents of cytoplasmic proteins, the surface and shape of erythrocytes (,And. Kurizki, A. N. The Kuybida, etc. Withdrawal from anaphylactic shock from clinical death after injection of lidocaine. Vestn. hir. them. I. Grekov,, 1987, N 4, 131 S.; N. X.Vahidov, I. A. Abdullaev, M. P. Muradov. Successful resuscitation of patients after adverse toxic reactions to lidocaine. Journal of the ear, nose and throat diseases, 1986, No. 6, S. 60 - 61; E. Nidhiguchi et al. Factors of the share change of human erythrocytes induced with lidocain Cell. struct. and Funct., 1989, Vol. 14, N, p. 569 - 577; M. D. Mashkovsky, 1998).

Great attention is given local anesthetic marcain (bupivacain), which has practical application as a tool for spinal, epidural, caudal, intra-articular anestes the n of plain and hyperbarric solutions administered to seated pateints Brit. J. Anaesrth., 1988, Vol. 61, N 4, p. 385 - 389; A. R. Wolf, R. D. Valley, D. W. Fear et al. Bupivacaine for caudal analgesia in infants and children: the optimal effective concentration. Anaesthesiology, 1988, Vol. 69, No. 1, p.101 - 105).

It should be noted that marcain, like dikaina not only highly active but also very toxic anesthetic (N. B. Raciborska. Mestnoanesteziruyuschie properties of some new derivatives of piperidine and indole. Abstract. dis. ...candles. the honey. Sciences. Rostov-on-don, 1991; J. Kambarn, B. Mets, R. Hickman et al. Comparative systemic toxicity of intravenously infused bupivacoune (B) cocaine (C) and lidocaine (L) inpigs: [Abstr.] Int. Anesth. Res. Soc. 66thCongr., San Francisco, Calif., March 13 - 17, 1992, anesth. and the play mode display., 1992, Vol. 74, No. 25, p.87), which requires special attention when used in practical medicine. In addition, marcain can cause with generalized rash, angioedema, laryngeal stridor, bronchospasm (H. Gacl, V., Reichert, R. Kaufmann. Localanastheticaintoleranz auf Leitungsanasthesia mit Prilocain und Bupivacain. Allergologie, 1992, Bd. 15, N 3, S. 89 - 91).

A relatively new anesthetic is ralation, which is a derivative of piperidine and with a pronounced analgesic effect and low toxicity. At block anesthesia 1% solution of rihanana causes a more rapid onset anesthesia, depth and duration of analgesic action exceeds 1.3 and 1.5 times, respectively, 2% Rana in surgical practice. Journe. experiment. hir. and anestesiol., 1974, No. 4, S. 56 - 58; K. of Kurakbaev. The use of anesthetic ikanaina during surgery in the maxillofacial region. Abstract. dis. ... candles. the honey. Sciences. Alma-ATA, 1976), and in case of infiltration and spinal anesthesia rihlokain used most often in combination with inulin, causes a pronounced analgesic effect, conceding, however, the effect of tetracaine and marcaine.

In a series of 1-substituted, imidazo[1,2-a]benzimidazole unknown compounds with mestnoanesteziruushim action.

The closest structure substance among the derivatives of imidazo[1,2-a] benzimidazole is the dihydrochloride of 1-diethylamino-ethyl-phenylimidazo[1,2-a] benzimidazole with hypotensive and antiarrhythmic effect (C. A. Anisimov, Y. A. Zhdanov, G. C. Kovalev and other Dihydrochloride 1-diethylaminoethyl-2-phenylimidazo[1,2-a]benzimidazole with hypotensive and antiarrhythmic effect. Auth. mon. N 1483894 (1989)).

The technical result of the invention is a new connection in a series of 1H-2-phenylimidazo[1,2-a] benzimidazole, showing unknown for this class local anesthetic action that is more effective than known mestnoanesteziruyuschie drugs the AI hydrochloride 2-phenyl-1-(3-chlorpropyl)imidazo[1,2-a] benzimidazole with diethylamine (method A) or 1-phenyl-2-chloro-benzimidazole with N, N-diethylaminopropylamine (method B) and the subsequent translation of the obtained 1-diethylaminopropyl-2-phenylimidazo[1,2-a] benzimidazole in water-soluble dihydrochloride I

< / BR>
The following is the procedure for the synthesis of the proposed connection.

Example. The dihydrochloride of 1-diethylaminopropyl-2-phenylimidazo[1,2-a] benzimidazole.

A. a Mixture of 3.46 g (10 mmol) of the hydrochloride of 2-phenyl-1-(3-chlorpropyl)imidazo[1,2-a]benzimidazole (C. A. Anisimov, A. A. Spasov, M. C. Levchenko, E. A. Alexandrov. Chem.-Pharm. J., 1995, No. 10, S. 18) and 12 ml of diethylamine heat 5 to 6 hours in a sealed ampoule at 145 - 150oC. and Then cooled, the ampoule is opened, its contents poured into 100 ml of water and extracted with chloroform (3 x 15 ml). The extract was washed with water (2 x 30 ml), dried with anhydrous Na2SO4, evaporated to a volume of 10 to 15 ml and passed through a layer of alumina (diameter 4 cm, height 3 cm), elwira 1-(3-diethylaminopropyl)-2-phenylimidazo[1,2-a] benzimidazole chloroform. After evaporation of the eluate is oil, which is dissolved in dry ether or acetone and the solution acidified with ethereal HCl solution or a saturated solution of HCl in isopropyl alcohol. Precipitated white precipitate is filtered off and recrystallized from isopropyl alcohol. Dried/P>C22H26N42HCl.

Calculated,%: C 60,4; H 6,9; Cl 16,2; N 12,8.

Range PMR (DMSO-d6+ CCL4), , M. D.: of 1.23 (6H, m, 2CH3), and 2.27 (2H, q, CH2), of 3.13 (6H, m, (CH2)2NCH2), and 4.40 (2H, m, N-CH2), 7,40 - 8,35 (10H, m, aromatics), of 11.15 (1H, user. s, NH), 13,50 - 17,00 (1H, broad stripe, NH).

IR-spectrum (Wesel. oil), cm-1: 2500 - 27300 (NH, broad band), 3200 - 3470 (NH, broad band).

B. a Mixture of 1.35 g (5 mmol) 1-phenacyl-2-chlorobenzimidazole (P. M. Kochergin, V. S. Sexton. The method of obtaining derivatives of imidazo[1,2-a]benzimidazole. Auth. mon. N 230827 (1968)) and 1.95 g (15 mmol) of 3-diethylaminopropylamine heated to 150oC and kept at this temperature for 1 hour, cooled, poured into 25 ml of water, extracted with chloroform (3 x 10 ml). The chloroform extract is washed with water, dried with anhydrous sodium sulfate, evaporated to a small volume (10 ml) and passed through a column (diameter 2 cm, height 20 cm) with alumina elwira chloroform and collecting the first fraction. The oil remaining after evaporation of the chloroform from the eluate, and represents a 1-diethylaminopropyl-2-phenylimidazo[1,2-a] benzimidazole translate to dihydrochloride I, as described above in the methodology And, receiving 1.5 g (72%) of salt.

The value of acute toxicity (, who and whom observed within 48 hours. LD50to connect with I equal of 41.8 mg/kg

Screening mestnoanesteziruyuschee action of salt I showed that it possesses analgesic effects in terminal (experiments on the cornea of rabbits using the method Rainier-Jack), infiltration (experiments on Guinea pigs) and conductor (experiments on the sciatic nerves of frogs) methods of anesthesia.

The in-depth study of local anesthetic activity under terminal anesthesia in the cornea of rabbits (Iskrev N. A. Stereo-isomers and properties pharmacological activity in a series kokinov: Dis. ... candles. the honey. of Sciences, Minsk, 1959; N. Pryanishnikov.T., Balls N.A. Trimekain. Pharmacology and clinical use. - L. : Medicine, 1967) found that the threshold local anesthetic concentration (MIC) for connection I is equal 0,0156%, and for rihanana, lidocaine and tetracaine Comparators, - of 0.25, 0.25 and 0,0156%, respectively. The index of the Rainier respectively 117,3 13,5, 72,0 14,5, 98,5 24,3 and 11,8 1,8. Based on the mapping PMK and indexes Rainier investigated substances can be arranged in the following descending series: the connection I > tetracaine > lidocaine rihlokain.

In terms of infiltration anesthesia in the skin of Guinea pigs using the method described Bulbring E., J. Wajda (J. Pharmacol. and Exp. Therap., 1945, Vol. 85, No. 1, p. 78 - 84) and Icarium N. A. (1959), compound I and marcain showed mestnorazdrajayuschie action, since the concentration 0,0156%, rihlokain - 0,0312%, novocaine - with 0,0625%, while the index Bullring and Wade for these substances are respectively equal to 7,0 (5,3 - 8,7), 6,4 (4,8 - 8,0), 6,8 (5,2 - 8,4) and 3.6(2,6 - 4,6). Full anesthesia (100%, the index of which is equal to 36) compound I and marcain caused, since the concentration 0.125%, rihlokain - 0,25% novocaine - from 0.5%.

Comparison of local anesthetic activity of the investigated substances in the EU50expressed in mm/l, showed that compound I in 8,42 and 2.39 times higher than novocaine and rihlokain, respectively, and comparable with marcaine.

In the study block anesthesia on the tibial nerves of mice (Ignatov Y. D., Vasiliev, Y. N., Beetles C. N. and other Methodological recommendations for ex the Agen local anesthetic action shows the connection I, its minimum effective concentration (ECmis 0,030 (0,027 - 0,034)% or 0,73 mm/l, whereas EUmnovocaine, rihanana and marcaine Comparators, - 0,182 (0,161 - 0,026), 0,120 (0,113 - 0,129) and 0.036(0,032 - 0,040)% or 6,69, 3.89 and 1.15 mm/l, respectively. Mapping EUm(mm/l) of the investigated substances showed that compound I is superior in 9,16 times novocaine, 5,33 times rihlokain and 1.57 times marcain.

As follows from the table. 2, the ratio of elimination, the corresponding speed elimination of a substance in the introduction, the connection I 1.9 and 1.2 times higher than rihlokain and novocaine, respectively, and was not materially different from such marcaine. While the half-life of compound I, novocaine, rihanana and marcaine respectively was 8.0, 9,8, and 7.6 to 15.4 minutes

Comparison of the concentrations of the investigated substances, causing motor paralysis (MP) limbs in mice for 15 min, showed that the concentration of compound I (0,111%) was in 4,73, 2,13 and 1.26 times less than novocaine, rihanana and marcaine respectively.

In conditions conductive anesthesia in the sciatic nerves of rats that I in a 0.125, 0.25 and 0.5% solutions causes mestnorazdrajayuschie effect later 2,4 0,1 substance at the time of onset of analgesic effect of 1.50 1.57 and 1,80 times respectively inferior to Marciano.

The depth of anesthesia when applying the compound I and marcaine (0,125% solution) were respectively 95,0 2,31 and 82,0 4,24%, i.e., the claimed compound according to this index of 1.16 times higher than the comparison drug.

The duration of analgesia when injecting compound I in the region of the sciatic nerve in 0,125 0,25 and 0,5% solution was equal 136,9 5,09, 175,2 5,55 and 214,6 8,66 min, while similar to the introduction of marcaine she was 93 and 5.30, 134,2 5,19 and 148,0 at 5.27 min, i.e., the claimed connection of 1.46, 1.30 and 1.45 times had a more prolonged effect than the reference drug.

When wiring the pain in the sciatic nerves of rabbits (N. Pryanishnikov.T., Balls N.A., 1967) found that the start time of anesthesia under the influence of compound I (0.25% solution) comes later (16,8 0,6 min) than under the influence of marcaine (14,0 1,0). However, the maximum duration of anesthetic effect by using the first connection was 2.18 times more than the second (246,0 of 1.9 min against level 113.0 1,2 min). The total duration of anesthesia under the influence of compound I was 408,0 2,0 min, and in the case of marcaine - 284,0 3.7 min, i.e., she was 1.44 times more.

In the study of spinal anaesthesia in rats with subarachnoidal the A. Phesiol. Behav., 1976, Vol. 17, p. 1031 - 1036) found that compound I and marcain 0.25% solution can cause the maximum analgesic effect in the first 5 min of the experiment, duration of anesthesia under the influence first made 86.2 6,4 min, second - 28,47 5,0 min, i.e., the connection I 3.03 times a more lasting than marcain. Increasing the concentration to 0.5% did not lead to changes in the time of onset of analgesia, whereas the duration of his under the influence I grew, making 118,6 of 7.5 min, and under the influence of marcaine - 48,4 of 6.7 min, i.e., compound I is 2.45 times higher than marcain.

In terms of spinal anaesthesia in rabbits with epidural introduction (Sachkov Century. And., Shoesince E. A., Kogan E. A. and other Anestesiol. and Reanimator. , 1986, No. 4, S. 7 - 12) found that in a 0.25% solution of salt I shows analgesic effect through 3,6 0,2 min, and marcain taken as ethanol, through 2,4 0,2 min, i.e., the first substance is 1.5 times inferior to the second. The use of compound I has caused a complete local anesthetic action through 4,6 0,2 min, and marcain - later 3,4 0,2, i.e. the investigated compound was superior to the comparator drug 1.35 times. The end of a full anesthesia under the influence I was observed after 77,0 2.5 minutes, and when the application times more than the second. The duration of anesthesia using the connection I was 154,0 of 1.9 min, and in the case of marcaine - 108,0 3 min, i.e., she was the first 1.43 times more than the second.

Thus, compound I may be used as a local anesthetic funds a wide range of actions in terminal, conductor and spinal anesthesia.

In a terminal anesthesia it exhibits a pronounced local anesthetic effect, surpassing activity and the breadth of therapeutic action tetracaine in 2,71 and 1.76% respectively. Unlike last connection I do not intrude on the conjunctival membranes of the eye of the rabbit. Lidocaine and rihlokain in the form of a 0.25% solution of local anesthetic action significantly inferior connection I.

At block anesthesia this connection has a pronounced analgesic effect:

in experiments on the tibial nerve of mice at the minimum effective concentration (ECmin 9,16, 5,33 and 1.57 times that of procaine, rihlokain and marcain respectively. The speed of elimination in the introduction 1.9 and 1.2 times higher than rihlokain and novocaine, but not significantly ncentratio) and duration of analgesic effect in 1.16 and 1.30 and 1.46 times that of lidocaine, but 1,50 - 1,80 times inferior to him in the time of onset of anesthesia;

in experiments on the sciatic nerves of rabbits (0.25 and 0.5% solutions) at the time of onset of analgesia is slightly inferior to marcaine that have the same depth of anesthesia, and duration of the anesthetic effect by 2.18 times greater than his.

In terms of spinal anaesthesia connection I also manifests a pronounced local anesthetic effect:

in experiments on rats with subarachnoid introduction of 0.25 and 0.5% solutions of I at the time of onset of analgesia is not materially different from marcaine, and duration of anesthesia 3.03 and 2.45 times respectively surpasses it;

in experiments on rabbits with epidural introduction of 0.25 and 0.5% solutions on the time of onset of anesthesia 1.5 and 1.86 times inferior to Marciano, and the depth and duration of anesthesia 1.35 and 1.43, 1.38 and 1.40 times respectively surpasses it.

The dihydrochloride of 1-diethylaminopropyl-2-phenylimidazo[1,2-a]benzimidazole of the formula I



 

Same patents:
The invention relates to organic chemistry, particularly to a process for the preparation of secondary amines from the corresponding sulfonamides

The invention relates to a derivative pyrrolopyridine or their pharmaceutically acceptable salts, with high activity, inhibiting the secretion of gastric juice; activity, protects the mucous membrane of the stomach; and high antibacterial activity against Helicobacter pylori; and antiulcer agent containing the derivative or salt as an active ingredient

The invention relates to nitroglicerine General formula A-X1-NR2or their salts, where a and X1have the meanings indicated in the claims, as well as to pharmaceutical compositions based on them

The invention relates to new heterocyclic compounds with biological activity, more specifically, to the derivatives of benzothiophene, benzofuran, indoltiazepinone, oxazepines and diazepinone, the pharmaceutical composition having inhibitory cell adhesion or HIV activity, method of inhibition of leukocyte adhesion to endothelial cells in the treatment of diseases caused by it and the method of treating mammals infected with HIV

Substituted pyrrole // 2141960

The invention relates to a piperidine derivative of General formula (I) where Z represents the group -(CH2)m-CH(OR3) or a carbonyl group, R1is hydrogen or (C1- C3)alkyl, R2- (C1- C3)alkyl, or R1and R2together form a chain -(CH2)n, where n is the number of 3 - 5, or -(CH2)2-O-(CH2)2-, m = 0 - 1, n = 1 - 2, R3- hydrogen or-COCH3and R4- hydrogen, -CH3, -OH or-OCH3provided that when Z represents a carbonyl group, h = 2, or their pharmaceutically acceptable salts

FIELD: organic chemistry, biochemistry, medicine.

SUBSTANCE: invention proposes applying derivatives of benzopyranoimidazole and benzothiopyranoimidazole as inhibitors of activity of phosphodiesterase VII, new derivatives of benzopyranoimidazole of the general formula (I)

with radical values given in the invention claim that elicit the above said activity and a pharmaceutical preparation based on thereof. Claimed derivatives elicit specific inhibition of rolipram-insensitive cAMP-phosphodiesterase (phosphodiesterase VII) in combination with good tolerance that allows their applying in asthma treatment. Indicated compounds show activity with respect to inhibition of tumor necrosis factor (TNF) producing that allows their applying for treatment of some autoimmune diseases.

EFFECT: valuable medicinal and biochemical properties of compounds.

3 cl, 2 tbl, 9 ex

FIELD: organic chemistry, medicine, hormones.

SUBSTANCE: invention describes imidazole derivatives of the formula (I) , racemic-diastereomeric mixtures and optical isomers, pharmaceutical salts wherein ---- represents an optional bond; R1 represents hydrogen atom (H), -(CH2)m-C(O)-(CH2)m-Z1, -(CH2)m-Z1; R2 represents hydrogen atom (H), or R1 and R2 are joined with nitrogen atoms to which they are bound forming compounds represented by formulae (Ia), (Ib) or (Ic) wherein R3 represents -(CH2)m-E-(CH2)m-Z2; R4 represents hydrogen atom (H) or -(CH2)m-A1; R5 represents (C1-C12)-alkyl, (C0-C6)-alkyl-C(O)-NH-(CH2)m-Z3 and optionally substituted phenyl; R6 represents hydrogen atom (H); R7 represents (C1-C12)-alkyl or -(CH2)m-Z4; m = 0 or a whole number from 1 to 6; n is a whole number from 1 to 5. Proposed compounds bind with subtypes of somatostatin receptors selectively.

EFFECT: valuable properties of compounds.

20 cl, 13776 ex

FIELD: veterinary science.

SUBSTANCE: invention proposes a preparation for treatment and prophylaxis of mastitis in cows at onset of the lactation period and in dry cows that comprises the following components, wt.-%: furacrylin, 0.4-0.6; dioxydin, 0.8-1.2; bee wax, 4-6, and sunflower oil, the balance. The preparation is heated to 38-40°C and administrated in cow mammary gland being in damaged and healthy lobules of udder through a nipple duct by using a syringe in the dose 5 ml. Using the preparation provides enhancing therapeutic and prophylactic effectiveness, decreasing labor intensity in treatment and prophylaxis of mastitis in cows at the lactation period and in dry cows.

EFFECT: enhanced and valuable properties of preparation.

3 tbl, 3 ex

FIELD: pharmaceutical industry.

SUBSTANCE: invention relates to creation of therapeutical and prophylactic balsams, which can be used as generally restorative and tonic agents to increase resistance of organism to reduced levels of atmosphere oxygen (increase of hypoxia resistance) as well as to prevention and correction of functional disorders associated with stress and exhausting environmental factors affecting organism. Invention proposes two variants of therapeutical-prophylactic balsam producing generally restorative and tonic effects, each containing vegetable oils, vitamins, amino acids, hepatic implant cells (Hepatosan), adaptogen (Astragerm), antioxidant, odorant, and thickener.

EFFECT: achieved normalization of vitality in exhausted organism.

6 cl

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to using phenylethenyl- or phenylethynyl-derivatives as antagonists of glutamates receptors. Invention describes using compound of the general formula (I):

wherein each among R1, R2, R3, R4 and R5 means independently of one another hydrogen atom, (C1-C6)-alkyl, -(CH2)n-halogen, (C1-C6)-alkoxy-group, -(CH2)n-NRR', -(CH2)n-N(R)-C(O)-C1-C6)-alkyl, phenyl or pyrrolyl that can be unsubstituted or substituted with one or more (C1-C6)-alkyl; each among R, R' and R'' means independently of one another hydrogen atom or (C1-C6)-alkyl; A means -CH=CH- or C≡C; B means ,, , , or wherein R6 means hydrogen atom, (C1-C)-alkyl, -(CH2)n-C(O)OR, or halogen atom; R7 means hydrogen atom, (C1-C6)-alkyl, -(CH2)n-C(O)OR', halogen atom, nitro-group or oxodiazolyl group that can be unsubstituted or substituted with (C1-C6)-alkyl or cycloalkyl; R8 means hydrogen atom, (C1-C6)-alkyl, -(CH2)n-OH, -(CH2)n-C(O)OR'' or phenyl; R9 means (C1-C6)-alkyl; R10 and R11 mean hydrogen atom; R12 means -(CH2)n-N(R)-C(O)-(C1-C6)-alkyl; R13 means hydrogen atom; each R14, R15, R16 and R17 independently of one another means hydrogen atom or (C1-C6)-alkoxy-group; each R18, R19 and R20 independently of one another means hydrogen atom; R21 means hydrogen atom or (C1-C6)-alkyl; R22 means hydrogen atom, (C1-C6)-alkyl or (C1-C6)-alkyl comprising one or more substitutes chosen from groups hydroxy- or halogen atom; R23 means hydrogen atom, (C1-C6)-alkanoyl or nitro-group; each among R24, R25 and R26 independently of one another means hydrogen atom or (C1-C6)-alkyl; n = 0, 1, 2, 3, 4, 5 or 6; X means -O- or -S-; Y means -CH= or -N=, and its pharmaceutically acceptable salts used in preparing medicinal agents designates for treatment or prophylaxis of disorders mediated by mGluR5-receptors. Also, invention describes compounds of the formula (I-A), compound of the formula (I-B-1) given in the invention description, and a medicinal agent used in treatment or prophylaxis of disorders mediated by mGluR5-receptors.

EFFECT: valuable medicinal properties of compounds.

44 cl, 1 tbl, 44 ex

FIELD: medicine, cardiology, chemical-pharmaceutical industry.

SUBSTANCE: invention relates to development of a complex from vegetable raw, vitamins, amino acids, trace elements and macroelements used in treatment of cardiovascular system diseases in carrying out the supporting therapy. Agent used in treatment of cardiovascular system in carrying out the supporting therapy contains as active components vitamins, bioflavonoids, trace elements, macroelements, extracts from medicinal plants, red grape polyphenol complex, broccoli concentrate, borage oil, L-cysteine, L-glutathione, D,L-methionine, and special supplements as cellulose, silicon dioxide, stearic acid, magnesium stearate and hydroxypropylcellulose, and this agent is made as a tablet formulation in the definite content of components per one tablet, in mg. Agent is designated in carrying out the supporting therapy in hypertensive disease of I-II degree, ischemic heart disease I-II of the functional class , neurocirculatory dystonia of different types. Agent is prescribed in the dose one tablet 1-2 times before eating or with food by course for one month. "AngioTonik" is agent able to provide body by all nutrient substances that are necessary for normal function of cardiovascular system.

EFFECT: valuable medicinal properties of agent.

5 cl, 5 tbl, 3 dwg

FIELD: organic chemistry, pharmaceuticals.

SUBSTANCE: invention relates to compounds of formula I , wherein substituents meanings are as defined in specification, and pharmaceutically acceptable salts or individual diastereomers thereof. Claimed compounds are useful as CGRP receptors antagonists in treatment or prophylaxis of headache, migraine, etc. Also disclosed are pharmaceutical compositions containing such compounds and uses thereof in treatment or prophylaxis of abovementioned diseases mediated by CGRP.

EFFECT: new CGRP receptor antagonists.

5 cl, 6 tbl, 40 ex

FIELD: medicine, organic chemistry.

SUBSTANCE: invention proposes a derivative of 2,9-substituted imidazo[1,2-a]benzimidazole possessing the more effective topical anesthetic effect. As this derivative the invention proposes 9-(2-pyrrolidinoethyl)-2-(4-fluorophenyl)-imidazo[1,2-a]benzimidazole of the formula (I):

EFFECT: valuable medicinal property of agent.

6 tbl

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to a novel compound of the general formula (I): wherein R means hydrogen atom (H), -OH, carbamoyl group; n = 1 or 2, or to its pharmaceutically acceptable salt. Compounds of the formula (I) are potential inhibitors of cellular adhesion mediated by integrins that allows its using as components of pharmaceutical composition used in treatment or prophylaxis of inflammatory, autoimmune or allergic state or rejection mediated by LFA-1.

EFFECT: valuable medicinal properties of compound and pharmaceutical composition.

19 cl, 2 sch, 3 dwg, 3 tbl, 7 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel compounds of the general formula (I): wherein R1 is chosen from group consisting of hydrogen atom (H), -(CH2)3-, -(CH2)4-, -CH2-S-CH2-, -S-CH2-CH2-; R2 is chosen from group consisting of nitrogen (N), sulfur (S) atom; n = 0 or 1; Z is chosen from group consisting of (C2-C10)-alkyl; R3 is chosen from group consisting of H; m = 0-2; R4 is chosen from group consisting of oxygen atom (O), -CH2-; R5 is chosen from group consisting of the following groups:

wherein R6 is chosen from group consisting of H, alkyl-(C1-C5)-alkoxyl; W is chosen from group consisting of -NH wherein each "alkyl" can be linear or branched and can be also cyclic or linear, or branched and comprises such cyclic residues, and each "aryl" comprises monocyclic aromatic group comprising 5-12 carbon atoms bound with one or some heteroatoms chosen from N, O or S atoms, and to their salts and solvates. Also, invention relates to a pharmaceutical composition, to a method for their synthesis and using compounds by claims 1-6. Invention provides synthesis of novel active compounds and pharmaceutical compositions based on thereof that possess affinity to serotonin receptors of subtype 5-HT1A.

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

10 cl, 4 tbl, 26 ex

Up!