Derivatives of 6,7-dihydro-5h-dibenz (c, e)azepin-7-it manifesting garmentindustry activity

 

(57) Abstract:

Usage: as substances with garmentindustry activity. The inventive product: derivatives of 6,7-dihydro-5h-dibenz/C,e/azepin -7 - it General formula where R = F or CI, Reagent 1: substituted benzoyl chloride. Reagent 2: 6,7 - dihydro-5h - dibenz/C,e/azepin - 7 he. Reagent 3: pyridine. Reaction conditions: boiling under reflux for 4 hours at 120°C.

The invention relates to new chemical compounds with biological activity, particularly to derivatives of dibenzazepine-6,7-dihydro-5H-dibenz [c, e] azepin-7-it is a General formula

R (I)where R is F, Cl, which have garmentindustry activity against microsomal cytochrome P-450-dependent monooxygenase system, liver, metabolizing foreign compounds - xenobiotics. This property allows the use of these compounds in medicine as inducers of metabolism of xenobiotics.

The closest structural analog - 6,7-dihydro-5H-dibenz[c,e]azepin-7-it - has weak garmentindustry activity. As basic compounds taken reference garmentindustry drug - phenobarbital - 5-ethyl-5-panelbar the m views pharmacological activity and low toxicity.

The goal is achieved by introducing substituted with halogen sensornogo residue at the N-position.

P R I m m e R. Synthesis of N-o-chlorobenzoyl-6,7-dihydro-5H-dibenz[c,e]azepin-7-it.

to 5.2 g (0,025 mol) of 6,7-dihydro-5H-dibenz[c,e]azepin-7-OA, 0.03 mol o-chlorine substituted of benzoyl chloride and 20 ml of pyridine is boiled in odnogolosy flask, equipped with reflux, for 4 hours at 120aboutC. Then the reaction mass is then cooled, add to it 10% solution of hydrochloric acid until no odor of pyridine. The precipitation is filtered off, washed on the filter with water, dried and recrystallized from a mixture of ethanol:acetone = 4: 1. When TLC shows the presence of a source of 6,7-dihydro-5H-dibenz[c,e]azepin-7-it is after cleaning, repeat it again. Rfbenzoylpropionic of 0.7-0.8; Rfsource dibenzazepine 0.37 system benzene:ethanol = 8:2. Characteristics of the obtained N-o-chloro-benzoyl-6,7-dihydro-5H-dibenz[c, e] azepin-7-it is presented in a table. 1.

The synthesis of other halogen derivatives of N-benzoyl-6,7-dihydro-5H-dibenz[c,e] ATAPI Nona carried out analogously to example. The experimental and calculated data on these compounds are also presented in table. 2.

Biological testing of the compounds NN 10210791-10211091, EN zymes the soup xenobiotics, conducted baseline drug phenobarbital on white outbred mice-males and Wistar rats. The activity of compounds was evaluated by the test geksenalovy sleep, the content of cytochrome P-450 in liver microsomes, the metabolic rate of substrate type I - amidopirina and substrate type II - aniline. Was determined daily acute toxicity in mice.

Biological tests were carried out on outbred mice-males weighing 18-22 g, the group consisted of 6-12 animals and rats male Wistar rats weighing 150-200 g of tested compound was administered in equimolar doses of 110 mg/kg inside three times once a day in the form of a suspension in 1% starch mucus. Comparison drug phenobarbital inside in equimolar dose of 80 mg/kg according to the same scheme. Control animals were injected equiano amount of starch mucus. Geksenal were injected with intraperitoneal dose of 80 mg/kg every 24 h after the last injection of inductors. The duration of drug-induced sleep was assessed by the absence of reflex turning of animals. Shortening the duration geksenalovy sleep proves the induction of monooxygenase systems in the liver, which metabolism geksenala and other xenobiotic coming and aboratory animals conducted biochemical studies of microsomal fraction of the liver of Wistar rats, obtained by differential centrifugation of the homogenate. In microsomes was determined by the level of cytochromes P-450 and5metabolism amidopirina was assessed by the formation of formaldehyde in the incubation media, the p-hydroxylation of aniline - education p-aminophenol. The content of microsomal cytochromes P-450 and5the activity of N-demethylase amidopirina and p-aniline hydroxylase was calculated per 1 mg of microsomal protein. Protein was determined by micromethod Lowry. The obtained results were processed by the criterion Student. The results of the biological tests are given in table. 1, 3 and 4.

The results presented in table. 1 and 3, indicate that the three-time ingestion of all of the compounds I is a significant shortening of the duration geksenalovy sleep laboratory animals - mice and rats, comparable to the action of a reference preparation of phenobarbital. The most active is the compound N 10210791 - o-ftoroproizvodnykh of dibenzazepine, which is more active than phenobarbital. Do not yield garmentindustry activity phenobarbital, judging by the duration geksenalovy sleep, connection N 10210891 and N 10210991 (PL. 3). From table. 4 shows that these compounds in equimolar the N-demethylation amidopirina and n-hydroxylation of aniline, that also indicates the induction of monooxygenase systems in the liver, developing under the impact of the proposed connection.

Thus, compounds I - halogenated derivatives of dibenzazepine are strong inducers of microsomal system of the liver and do not yield on this type of biological activity of phenobarbital. In addition, compounds I are significantly less toxicity compared with phenobarbital LD50for mice, the oral administration is for all connections over 1500 mg/kg of phenobarbital - 320 mg/kg

Thus, for the first time among benzoylpropionic of dibenzazepine detected inducible monooxygenase system of the liver, with significant garmentindustry activity and low toxicity.

DERIVATIVES OF 6,7-DIHYDRO-5H-DIBENZ (C, E)AZEPIN-7-IT MANIFESTING GARMENTINDUSTRY ACTIVITY.

Derivatives of 6,7-dihydro-5H-dibenz(C,e)azepin-7-it General formula

< / BR>
where R is F or Cl,

showing garmentindustry activity.

 

Same patents:

The invention relates to medicine, namely to Pediatrics, and can be used for the treatment of musculoskeletal disorders in children

FIELD: medicine, neurology.

SUBSTANCE: the present innovation describes arylalkylamines that specifically affect certain types of receptor-operated Ca2+-canals, their application and pharmaceutical compositions for treating neurological disorders or diseases.

EFFECT: higher efficiency.

55 cl, 29 ex, 11 tbl

FIELD: medicine.

SUBSTANCE: method involves rectally introducing mixture produced on base of 5% Novocain solution containing isoniazid, rifamycin, ethambutol in therapeutic doses daily during 21 days. The mixture is pretreated in ultrasonic field during 5 min at 2 MHz frequency.

EFFECT: improved bacteriostatic blood and prostate secret activity.

1 tbl

FIELD: medicine.

SUBSTANCE: method involves applying cannabinoid receptor agonists for treating for transitory relaxation of lower esophageal sphincter and states like gastroesophageal reflux disease, regurgitation, preventing reflux or insufficient mass increase caused by the relaxation.

EFFECT: enhanced effectiveness of treatment.

18 cl, 3 tbl

FIELD: medicine, phthisiology.

SUBSTANCE: method involves firstly the achievement of lymphotropicity of three chemopreparations by addition of 5% glucose and aloe to solutions of these chemopreparations. Then the conduction paravertebral anesthesia is carried out at the level and at side of administration of preparations. Then three chemopreparations are administrated separately in different intercostals sites, 1-3 times per a week, course of 4-12 injections by subcutaneous paravertebral route, parasternal route in I-X intercostals - in projection of regional lymphatic collectors. Method allows reducing the duration of intensive phase in tuberculosis treatment up to 1-3-6 months, to prevent the development of drug-resistant tuberculosis and adverse effects of chemopreparations and to relieve the residual changes of tuberculosis. Invention can be used in treatment of infiltrative, destructive and drug-resistant pulmonary tuberculosis.

EFFECT: improved and enhanced method of treatment.

2 ex

FIELD: medicine; physiotherapy.

SUBSTANCE: two to here days after surgical operation, vibration massage is made by means of vibration apparatus on thorax area of root of lung being opposite to that one which was subject to operation. Vibration massage is made daily at frequency of 90-100 Hz and amplitude of 0,4-0,5 mm during 3-5 minutes for 13-14 days. Starting from the fourth f the fifth day after operation, when both drainages are removed from post-resection pleural cavity, electric-vibration acupressure is made in parallel on skin covers all around total area of thorax by means of massaging device. Vibration-acupressure is made daily at the second part of day after I-II row chemical preparations are given to patient. Frequency of procedure is 35-40 Hz and amplitude 0,5-0,6 mm. Duration of influence is increased gradually from 3 to 13-14 minutes during 11-12 days.

EFFECT: reduced number of pleural-pulmonary complications; uniform ventilation of all parts of segments of lung subjected to operation.

2 ex, 3 tbl

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel ester compounds represented by the formula (1): wherein values for R1, R2, A, X, R3, R4, Alk1, Alk2, l, m, D, R8 and R9 are determined in the invention claim. Also, invention relates to inhibitor of matrix metalloproteinase (MTP), a pharmaceutical composition able to inhibit activity of MTP selectively, agents used in treatment or prophylaxis of hyperlipidemia, arteriosclerosis, coronary artery diseases, obesity, diabetes mellitus or hypertension wherein the pharmaceutical composition is prepared in capsulated formulation, and to a biphenyl compound of the formula (100) given in the invention description.

EFFECT: valuable medicinal properties of compounds.

53 cl, 78 tbl, 17 ex

FIELD: medicine, phthisiology.

SUBSTANCE: method involves the combined oral and rectal administration of chemopreparations. Ethambutol and pyrazinamide are administrated by oral route in the doses 1.2 g and 1.5 g, respectively. Mixture of chemopreparations as an ultraemulsion is used for rectal administration that is prepared 1 h before administration. The mixture comprises isoniazid (10 mg/kg), rifampicin (600 mg), kanamycin (1 g) and lecithin (20 ml). Therapy is carried out in intensive treatment phase 5 times per a week up to three months and in supporting phase 2 times per a week up to closing destruction cavities. Method provides rapid regression of pulmonary tuberculosis process, to improve tolerance of chemopreparations based on their selective accumulation in lymphatic system of lungs and specific schedule of administration of these chemopreparations. Invention can be used in treatment of destructive form of pulmonary tuberculosis.

EFFECT: improved method of treatment.

1 tbl, 1 ex

Biocidal gel // 2305544

FIELD: pharmaceutical industry, in particular biocide agent.

SUBSTANCE: claimed gel includes hydroxyethyl cellulose, polyguanidine compound (e.g. polyhexamethylene guanidine succinate or poly-(4,9-dioxadodecan guanidine) succinate), glycerol, trilon B, polyethylene glycol, citric acid, perfume composition, and water. Additionally it contains neonol, calcium pantothenate and chamomile extract in specific component ratio.

EFFECT: gel with increased biocidal action.

3 tbl, 3 ex

FIELD: medicine, chemical-pharmaceutical industry, pharmacy.

SUBSTANCE: invention relates to using compound of the formula Z-linker-Z' (1) representing antagonist of chemokinine receptor CXCR4 for preparing a medicinal agent used in mobilization and collection of cell-precursors and/or stem cells in subject. The claimed invention describes also methods for increasing amount of cell-precursors and stem cells in animals using compounds that bind chemokinine receptor CXCR4. Using compound of the formula (1) allows enhancing effectiveness in treatment of HIV and to alleviate unfavorable effects on bone marrow in the process of chemotherapy carrying out.

EFFECT: improved methods for activation.

19 cl, 12 tbl, 1 dwg, 4 ex

FIELD: pharmaceutical industry and technology, pharmacy.

SUBSTANCE: invention relates to development of method for preparing rifabutin-containing antibacterial composition. Method involves separate mixing one part of rifabutin with special additives and filling agent and another part of rifabutin with lacking amount of filling agent and their following combining, powdering the mixture with magnesium stearate at stirring and making capsules. Method allows simplifying technology in preparing the preparation in capsulated form owing to optimal technological indices of the prepared composition mixture. The composition shows high stability in storing and therapeutic effectiveness.

EFFECT: valuable pharmaceutical and medicinal properties of composition.

2 tbl, 1 ex

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

SUBSTANCE: invention relates to compounds of the formula (I): wherein both X1 and X2 represent methylene; R3 represents -CR5=CHR6, and R5 and R6 in common with atoms to which R5 and R6 are bound form (C6-C12)-aryl wherein R3 is substituted optionally with 1-5 radicals of the formula: -X4OR9 wherein X4 represents a bond; R9 represents halogen-substituted (C1-C3)-alkyl, and R4 represents -C(O)X5R11 wherein X5 represents a bond, and R11 represents hetero-(C6-C6)-cycloalkyl-(C0-3)-alkyl; X3 represents group of formulae (a) , (b) or (c) wherein n = 0, 1 or 2; R20 represents hydrogen atom (H); R21 is chosen from group consisting of H, -C(O)R26, -S(O)2R26 wherein R23 is chosen from H and (C6-C12)-aryl-(C0-C6)-alkyl; R25 is chosen from H, (C6-C12)-aryl-(C0-C6)-alkyl or -X4S(O)2R26 wherein X4 has above given values; R26 is chosen from group consisting of H, (C6-C12)-aryl-(C0-C6)-alkyl; wherein X3 comprises optionally, except for, one substitute that being in alicyclic or in aromatic ring system represents a radical chosen independently from group consisting of -X6OR17 wherein R17 represents H, (C1-C6)-alkyl, and X represents a bond or (C1-C6)-alkylene; and its N-oxide derivatives, protected derivatives, individual isomers and mixtures of these isomers; and pharmaceutically acceptable salts and solvated of such compounds, its N- oxide derivatives, protected derivatives, individual isomers and mixtures of these isomers. Also, invention describes a pharmaceutical composition possessing inhibitory activity with respect to cathepsin S-proteases based on compounds of the formula (I), and compound of the formula (Ix) given in the invention description. Invention provides preparing novel compounds possessing useful biological properties.

EFFECT: improved preparing method, valuable medicinal and biological properties of compounds and pharmaceutical composition.

16 cl, 3 tbl, 17 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to novel sulphonamide derivatives of general formula (I) , where R1 is phenyl, thiophenyl or furanyl, unsubstituted or substituted with one or two substitutes selected from a group consisting of halogen, lower alkyl, lower alkyl substituted with halogen, -O-lower alkyl substituted with halogen, NO2 or CN; R2-R4 and R2'-R4' is hydrogen, lower alkyl, phenyl or lower alkyl substituted with halogen; R5 is phenyl, pyridinyl, benzo[1,3]dioxolyl or benzofuranyl, unsubstituted or substituted with 1-3 substitutes selected from a group consisting of halogen, lower alkyl, lower alkyloxy, CN, nitro, amino, hydroxy, lower alkyl substituted with hydroxy, lower alkyl substituted with halogen, or substituted with -C(O)-NR"2, -(CR2)m-C(O)-R', -(CH2)m-heteroaryl, unsubstituted or monosubstituted -(CH2)m-lower alkoxy, lower alkyl, -(CH2)m-O-benzene or CH2OH, -O-C(O)-lower alkyl, -O-C(O)-NR2, -O-(CH2)m-C(O)OH, -O-lower alkynyl, -O-lower alkyl, substituted with halogen, -O-(CH2)m-heterocyclyl, -O-(CH2)m-phenyl, unsubstituted or monosubstituted hydroxy, -O-(CH2)m-heteroaryl, unsubstituted or monosubstituted with lower alkyl, -(CH2)m-NH-C(O)R', -(CH2)m-NH-S(O)2-R', -S(O)2-lower alkyl, -S(O)2-heterocyclyl, -S(O)2NH-cycloalkyl, or is C3-6cycloalkyl; R' is hydrogen, lower alkyl, lower alkynyloxy, hydroxy, C3-6cycloalkyl, heterocyclyl, which is unsubstituted or substituted with one or two substitutes selected from COOH, -C(O)O-lower alkyl, halogen or lower alkyl, or is phenyl, benzyl, heteroaryl, -(CH2)m-lower alkoxy or -(CHR)m-C(O)O-lower alkyl; R" is hydrogen, C3-6cycloalkyl, which is unsubstituted or substituted with one or two substitutes selected from halogen, or is lower alkyl, lower alkyl substituted with halogen, lower alkyl substituted with hydroxy, -(CH2)m-heterocyclyl, -NR2, heteroaryl, benzyl or -(CHR)m-C(O)O-lower alkyl; R is hydrogen or lower alkyl; X is -CHR-; m equals 0, 1, 2 or 3; and its pharmaceutically acceptable salts of an acid compound, optically pure enantiomers, racemates or diastereomeric mixtures. The invention also relates to medicine containing a formula I compound.

EFFECT: obtaining novel compounds which inhibit γ-secretase.

16 cl, 230 ex

FIELD: pharmaceutics.

SUBSTANCE: invention relates to compounds of formula I or pharmaceutically acceptable salts thereof, which have antihypertensive action. In formula I X represents O or NR7; group is bonded to any carbon ring atom, different from carbon atom to which are bonded R1 and R2; R1 represents hydrogen or together with R2 forms =O; R2 represents hydrogen or together with R1 forms =O; R4 is -C1-6alkyl; R5 and R6, which are bonded to any available carbon ring atom, independently represent hydrogen or R5 and R6 in cases when they are bonded to same carbon atom, form =O; R7 is -C1-6alkyl, -C(O)O-C-1-6alkyl, -C(O)O-C-1-6alkylene-CR8R9R10, -C(O)C1-6alkyl, -C(O)OC3-6carbocycle, -C(O)aryl, -C(O)heteroaryl, where heteroaryl is unsaturated 5- or 6-member ring containing 1-4 heteroatoms selected from N, -C(O)NHC1-6alkyl, -C(O)NH-adamantyl, -SO2C1-6alkyl, aryl or unsaturated 5- or 6-Member heteroaryl ring containing 1-4 heteroatoms selected from N, where aryl, alkyl, alkylene, carbocycle and heteroaryl are unsubstituted or substituted with 1-4 groups independently selected from -CN, halogen, -CF3, -OCF3, -C(O)NH2, -C-1-6alkyl, aryl, unsaturated 5-member heteroaryl ring with 1-3 nitrogen atoms, where R8 and R9 together with carbon atom to which they are bonded form C3-6carbocycle or 4-8-member heterocycle containing an oxygen atom, and where R10 is C1-6alkyl.

EFFECT: invention also relates to pharmaceutical compositions containing said compounds, and a method of treating hypertension.

29 cl, 43 ex

Up!