4-acetyl-3-benzyl-2-methylthiopyridine(4,5-b)indole protecting the liver from carbon tetrachloride poisoning

 

(57) Abstract:

Usage: in medicine to protect the liver from poisoning by carbon tetrachloride. The inventive product 4-acetyl-3-benzyl-2-methylthioribose-(4,5 - b)indole f-crystals I. BF C19H17N3OS, yield 88% , so pl. 172 C. Reagent 1: compound f-ly II. Reagent 2: CH3J. reaction Conditions: in the presence of bases-alkalis or carbonates of alkali metals in aqueous, aqueous-alcoholic medium or in dimethylformamide at room temperature. table 1.

The invention relates to the chemistry of condensed heterocyclic systems and specifically relates to new compounds - 4-acetyl-3-benzyl-2-methylthiopyridine(4,5-b)indole of the formula I

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Through the study of its biological activity is established that it has the property to protect the liver from poisoning by carbon tetrachloride. This property suggests the possibility of using this compound for prevention and treatment in humans acute inhalation poisoning by carbon tetrachloride.

Significant growth in the use for the different needs of technical liquids accompanied by the growth of acute poisoning. Chlorinated hydrocarbons fatty number of both regional and the risk can imagine chlorinated hydrocarbons in emergency situations, when, due to their high volatility inhalation poisoning may be a large number of people.

In all patients with severe liver damage, up to fatty degeneration of the body. Widespread use of carbon tetrachloride in industry, agriculture and military Affairs that makes urgent the search for pharmacological agents that protect the body from exposure to carbon tetrachloride.

To stimulate the regeneration of liver used derivatives of purine and pyrimidine bases Riboxin and potassium orotate (And similar) (1), but their activity is insufficient.

The purpose of the invention is a new connection of a number of imidazo (4,5-b)indole, more effectively protect the liver from poisoning by carbon tetrachloride.

This goal is achieved by the chemical structure of the new compounds of formula I, having the specified property.

The inventive compound is a yellowish-white crystalline substance, insoluble in water, easily soluble in chloroform.

The method of obtaining the claimed compounds based on known reactions alkylation of heterocyclic thiones on the sulfur atom in Melo carried out in the presence of bases - alkali or carbonates of alkali metals in aqueous, aqueous-alcoholic medium or in dimethylformamide. The reaction is carried out at room temperature (18-25aboutC).

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The structure of compound I is confirmed by the data of elemental analysis and spectral characteristics shown in example 1. The fact that methylation is carried out exactly according to the sulfur atom, confirmed the removal of mercaptan by heating the claimed compounds with hydrochloric acid.

P R I m e R 1. Mix 1 g (2,982 mmol) of 4-acetyl-3-benzimidazo(4,5-b)-indole-2-thione, 1 g (7,24 mmol) of finely ground anhydrous potassium carbonate, and 1 ml (16,06 mmol) methyl iodide and 20 ml of anhydrous dimethylformamide at 20aboutC for 1 h was Filtered, the filtrate poured into 50 ml of water, precipitated precipitate is filtered off, washed with water and dried. Obtain 0.88 g of compound I (88% ), after recrystallization from alcohol shiny white crystals, so pl. 172aboutC.

The substance is homogeneous according to TLC. The adsorbent - Silufol uv-254, a solvent for applying the acetone eluent - ethyl acetate: hexane, 1 : 3, Rf of 0.30.

Found, % : C 68,11; H 68,25; H Are 5.36, 5,17; N 12,64, 12,68; S 9,88, 9,67.

C19H17N3OS.

Calculated, % : C 68,03; H 5,11;SUB>2), 6,90-7,54 m (8H, Ar), 7,80 g (1N, N5).

The mass range 100aboutTo, m/z (1): 335 (100)M+, 293 (40)M+THE PINES2, 278 (6)M+-CH2CO-CH3, 244 (10)M+-CH2WITH6H5, 202 (100)M+THE PINES2-CH2WITH6H5, 186 (4)M+-CH2WITH6H5-NS.

UV-spectrum in alcohol, max , nm (lg E): 248 (4,00), 293 (4,16).

P R I m m e R 2. Mix 1 n (2,982 mmol) of 4-acetyl-3-benzimidazo(4,5-b)indole-2-thione with 4.3 ml of 1 n sodium hydroxide solution is added to 1.36 ml (to 21.8 mmol) methyl iodide and another 4.3 ml of 1 n sodium hydroxide solution and shaken for 2 h at 20aboutC. the Precipitate is filtered off, washed with water (3 x 5 ml) and dried over phosphorus pentoxide in a vacuum. Get to 0.74 (74% ) of compound I, identical with the substance obtained in example 1.

Study of the biological activity of the claimed compounds.

Experiments were performed on white rats-males weighing 170-200 g carbon Tetrachloride was administered subcutaneously daily at 50% oil solution during 4 consecutive days in the amount of 0.4 ml per 100 g mass. Simultaneously with carbon tetrachloride was administered the inventive compound in a dose of 25 mg/kg the Effect of the drug was compared with the known hepatic - produced puturi know, what is the clinical picture of poisoning by carbon tetrachloride develops slowly. The main symptoms of intoxication is manifested by the end of the second day and in 4 to 7 days, usually seen flying the outcome. In all patients with severe liver damage, up to fatty degeneration of the body. Evaluation of the protective action of the claimed compounds was performed by examining the duration geksenalovy sleep (HS), the concentration of alanine aminotransferase (Alat), aspartate aminotransferase (AST) and total bilirubin (ABOUT) in the serum. Changes in the activity of transamination enzymes in the serum, the increase of bilirubin indicate deleterious effects of carbon tetrachloride on the cell membrane. Violation process bilirubinometry, increase the length of geksenalovy sleep says about the violation of detoxification of the liver.

Data on the biological activity of the claimed compounds, in comparison with the known hepatic presented in the table.

The analyzed connection by a set of indicators than the known analogues with hepatoprotective effect of intoxication with carbon tetrachloride - ribocree reduces the duration geksenalovy sleep at 1.27 times, the concentration of serum Alat - 1.2 times, ASAT - 1.23 times, total bilirubin - 2.0 times compared to control.

Acute toxicity was determined on nonlinear white mice-males after a single injection intraperitoneally claimed compounds by known methods (3). Found that LD50investigational product exceeds 3980 mg/kg of the Obtained result shows that the inventive compound can be attributed to toxic substances. It is characterized by large pharmaceutical latitude. (56) Rychnov C. E. , Frolov C. M. Stimulants regeneration in the treatment of viral hepatitis and other liver diseases. Voronezh: Publishing house of Voronezh state University, 1984, S. 22.

Ioffe, I. S. , Tomchin A. B. , E. Zhukova N. Semicarbazone and heterocyclic thiosemicarbazones series. III. Methyl derivatives of 2-mercapto-1,3,4-Tazacorte. - Journal. Gen. chem. - 1969, 39, vol. 3 - S. 640-645.

Prozorovskiy Century B. , Prozorovsky M. P. , Demchenko, C. M. a rapid method for the determination of the average effective dose and its error // Pharmacol. and toxicol. - 1978 - N 4 - n-497-502.

4-Acetyl-3-benzyl-2-methylthymidine(4,5-b)indole of the formula

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protecting the liver from poisoning by carbon tetrachloride.

 

Same patents:

The invention relates to new derivatives of benzodiazepine, specifically tricyclic compounds of General formula Iwhere RI- phenyl, possibly substituted by fluorine,

X - CH2or CHR3where R3- C1-C4alkyl, and R2- 2-indolocarbazole; phenyl (lower) alkanoyl, which can be substituted by amino or lower alkanolamine; or R2- phenylcarbamoyl, which may be substituted with halogen or lower alkoxygroup, or their pharmaceutically acceptable salts

The invention relates to new derivatives of 2-(21-cyano-31-dialkylamino-21- enylidene)indolinone-3 of the General formula I

(I) where R= R1= CH3(Ia),

R + R1= (CH2)5(IB) having antihypertensive activity

The invention relates to medicine, namely to obstetrics

FIELD: medicine.

SUBSTANCE: method involves introducing 0.1-0.3 ml of photosensitizing gel preliminarily activated with laser radiation, after having removed neovascular membrane. The photosensitizing gel is based on a viscoelastic of hyaluronic acid containing khlorin, selected from group containing photolon, radachlorine or photoditazine in the amount of 0.1-2% by mass. The photosensitizing gel is in vitro activated with laser radiation having wavelength of 661-666 nm during 3-10 min with total radiation dose being equal to 100-600 J/cm2. The gel is introduced immediately after being activated. To compress the retina, vitreous cavity is filled with perfluororganic compound or air to be further substituted with silicon oil. The operation is ended with placing sutures on sclerotomy and conjunctiva areas. Compounds like chealon, viscoate or hyatulon are used as viscoelastic based on hyaluronic acid. Perfluormetylcyclohexylperidin, perfluortributylamine or perfluorpolyester or like are used as the perfluororganic compound for filling vitreous cavity.

EFFECT: excluded recurrences of surgically removed neovascular membrane and development of proliferative retinopathy and retina detachment; retained vision function.

3 cl, 5 dwg

FIELD: medicine.

SUBSTANCE: method involves making incision in conjunctiva and Tenon's capsule of 3-4 mm in size in choroid hemangioma projection to sclera 3-4 mm far from limb. Tunnel is built between sclera and Tenon's capsule to extrasclerally introduce flexible polymer magnetolaser implant through the tunnel to the place, the choroid hemangioma is localized, after performing transscleral diaphanoscopic adjustment of choroid hemangioma localization and size, under visual control using guidance beam. The implant has permanent ring-shaped magnet in the center of which a short focus scattering lens of laser radiator is fixed. The lens is connected to light guide in soft flexible envelope. The permanent implant magnet is axially magnetized and produces permanent magnetic field of 2-3 mTesla units intensity. It is arranged with its north pole turned towards the choroid hemangioma so that extrascleral implant laser radiator disposition. The other end of the implant is sutured to sclera 5-6 mm far from the limb with two interrupted sutures through prefabricated openings. The implant is covered with conjunctiva and relaxation sutures are placed over it. Light guide outlet is attached to temple using any known method. 0.1-1% khlorin solution is injected in intravenous bolus dose of 0.8-1.1 mg/kg as photosensitizer and visual control of choroid hemangioma cells fluorescence and fluorescent diagnosis methods are applied. After saturating choroid hemangioma with the photosensitizer to maximum level, transscleral choroid hemangioma laser radiation treatment is carried out via laser light guide and implant lens using divergent laser radiation at wavelength of 661-666 nm with total radiation dose being equal to 30-120 J/cm2. The flexible polymer magnetolaser implant is removed and sutures are placed on conjunctiva. Permanent magnet of the flexible polymer magnetolaser implant is manufactured from samarium-cobalt, samarium-iron-nitrogen or neodymium-iron-boron system material. The photosensitizer is repeatedly intravenously introduced at the same dose in 2-3 days after the first laser radiation treatment. Visual intraocular neoplasm cells fluorescence control is carried out using fluorescent diagnosis techniques. Maximum level of saturation with the photosensitizer being achieved in the intraocular neoplasm, repeated laser irradiation of the choroid hemangioma is carried out with radiation dose of 30-60 J/cm2.

EFFECT: enhanced effectiveness of treatment.

4 cl

FIELD: medicine.

SUBSTANCE: method involves creating tunnel between sclera and Tenon's capsule in intraocular neoplasm projection. Intraocular neoplasm localization and size is adjusted by applying transscleral diaphanoscopic examination method. 0.1-0.3 ml of photosensitizing gel based on viscoelastic of hyaluronic acid, selected from group containing chealon, viscoate or hyatulon, is transsclerally introduced into intraocular neoplasm structure using special purpose needle in dosed manner. The photosensitizing gel contains khlorin, selected from group containing photolon, radachlorine or photoditazine in the amount of 0.1-1% by mass. Flexible polymer magnetolaser implant is extrasclerally introduced into the built tunnel in intraocular neoplasm projection zone under visual control using guidance beam. The implant has permanent ring-shaped magnet axially magnetized and producing permanent magnetic field of 3-4 mTesla units intensity, in the center of which a short focus scattering lens of laser radiator is fixed. The lens is connected to light guide in soft flexible envelope. The implant is arranged with its north pole turned towards the intraocular neoplasm so that implant laser radiator lens is extrasclerally arranged in intraocular neoplasm projection zone. The implant light guide is sutured to sclera 5-6 mm far from the limb with single interrupted suture. The implant is covered with conjunctiva and relaxation sutures are placed over it. Light guide outlet is attached to temple using any known method. Visual control of intraocular neoplasm cells is carried out by applying fluorescence and fluorescent diagnosis methods. After saturating the intraocular neoplasm with the photosensitizer to maximum saturation level, transscleral intraocular neoplasm laser radiation treatment is carried out via laser light guide and implant lens using divergent laser radiation at wavelength of 661-666 nm. The treatment course being over, the flexible polymer magnetolaser implant is removed and sutures are placed on conjunctiva. Permanent magnet of the flexible polymer magnetolaser implant is manufactured from samarium-cobalt, neodymium-iron-boron or samarium-iron-nitrogen. 0.1-1% khlorin solution as photosensitizer, selected from group containing photolon, radachlorine or photoditazine, is additionally intravenously introduced in 2-3 days at a dose of 0.8-1.1 mg/kg and repeated laser irradiation of the intraocular neoplasm is carried out with radiation dose of 30-45 J/cm2 15-20 min later during 30-90 s.

EFFECT: complete destruction of neoplasm; excluded its further growth.

4 cl

FIELD: medicine.

SUBSTANCE: method involves applying transscleral diaphanoscopic examination method for adjusting intraocular neoplasm localization and size. Rectangular scleral pocket is built 2/3 times as large as sclera thickness which base is turned from the limb. Several electrodes manufactured from a metal of platinum group are introduced into intraocular neoplasm structure via the built scleral pocket. Next to it, intraocular neoplasm electrochemical destruction is carried out in changing electrodes polarity with current intensity of 100 mA during 1-10 min, and the electrodes are removed. Superficial scleral flap is returned to its place and fixed with interrupted sutures. 0.1-2% aqueous solution of khlorin as photosensitizer, selected from group containing photolon, radachlorine or photoditazine, is intravenously introduced at a dose of 0.8-1.1 mg/kg. Visual control of intraocular neoplasm cells is carried out by applying fluorescence and fluorescent diagnosis methods. After saturating the intraocular neoplasm with the photosensitizer to maximum saturation level, transpupillary laser radiation of 661-666 nm large wavelength is applied at a dose of 30-120 J/cm2. the operation is ended with placing sutures on conjunctiva. Platinum, iridium or rhodium are used as the metals of platinum group. The number of electrodes is equal to 4-8. 0.1-1% khlorin solution, selected from group containing photolon, radachlorine or photoditazine, is additionally repeatedly intravenously introduced in 2-3 days at a dose of 0.8-1.1 mg/kg. Visual control of intraocular neoplasm cells is carried out by applying fluorescence and fluorescent diagnosis methods. After saturating the intraocular neoplasm with the photosensitizer to maximum saturation level, repeated laser irradiation of the intraocular neoplasm is carried out with radiation dose of 30-45 J/cm2.

EFFECT: complete destruction of neoplasm; excluded tumor recurrence; reduced risk of tumor cells dissemination.

3 cl, 3 dwg

FIELD: medicine.

SUBSTANCE: method involves intravenously administering 0.1-1% aqueous solution of khlorin, selected from group containing photolon, radachlorine or photoditazine at a dose of 0.2-0.5 mg/kg or 0.2-1% aqueous solution of porphyrin like photogem at a dose of 0.2-1 mg/kg. Laser irradiation of blood is carried out 5-15 min later after beginning photosensitizer injection into cubital vein of one arm via laser light guide set in advance in the cubital vein of the other arm during 10-40 min at wavelength of 661-666 nm and power of 20-50 mW one session per day during 3-10 days with the aqueous solution of khlorin used as the photosensitizer, or laser irradiation of blood with wavelength equal to 630-633 nm during 10-45 min with power of 20-50 mW one session per day with the aqueous solution of porphyrin used as the photosensitizer. Repeated intravenous administration of photosensitizer is carried out 1-3 months later combined with repeated laser irradiation of blood.

EFFECT: reduced risk of tumor cells dissemination and metastasis development.

2 cl

FIELD: organic chemistry, medicine, chemical-pharmaceutical industry, pharmacology, pharmacy.

SUBSTANCE: invention relates to a medicinal agent used for prophylaxis and treatment of diseases and disorders associated with dysfunction of benzodiazepine receptors. This medicinal agent comprises compound of the formula (I)

. Compound of the formula (I) elicits high cardioprotective, neurotrophic, renoprotective activity and enhanced bioavailability.

EFFECT: valuable medicinal properties of compounds.

5 cl, 1 tbl, 1 ex

FIELD: medicine, cardiology.

SUBSTANCE: the suggested method should be performed at the background of medicinal therapy with preparations out of statins group, tevetene, polyoxidonium and conducting seances of plasmapheresis by removing 800 ml plasma twice weekly with N 5 due to additional intramuscular injection of immunophan 0.005%-1.0 with N 10 and fluimucyl 300 mg intravenously daily with N 5-10, total course of therapy lasts for 2 mo. The method provides modulation of leukocytic functional activity, moreover, due to altered cytokine profile and, thus, through disintegration of protein-lipid complexes participating in the development of atherosclerotic platelets.

EFFECT: higher efficiency of therapy.

3 ex

FIELD: medicine.

SUBSTANCE: method involves intravitreously introducing two electrodes into intraocular neoplasm after carrying out vitrectomy and retinotomy to expose the intraocular neoplasm. The electrodes are manufactured from platinum group metal. Electrochemical destruction is carried out with current intensity of 100 mA during 1-10 min or 10 mA during 10 min in changing electrodes polarity and their position in the intraocular neoplasm space, and the electrodes are removed. 0.1-1% aqueous solution of khlorin as photosensitizer, selected from group containing photolon, radachlorine or photoditazine, is intravenously introduced at a dose of 0.8-1.1 mg/kg. Visual control of intraocular neoplasm cells fluorescence is carried out by applying fluorescent diagnosis methods. After saturating the intraocular neoplasm with the photosensitizer to maximum saturation level, intravitreous laser radiation is carried out in parallel light beam of wavelength equal to 661-666 nm is applied at a dose of 30-120 J/cm2.The transformed retina and tumor destruction products are intravitreally removed. Boundary-making endolasercoagulation of retinotomy area is carried out after having smoothed and compressed retina with perfluororganic compound. The operation is finished with placing sutures on sclerotomy and conjunctiva. Platinum, iridium or rhodium are used as the platinum group metals. Another embodiment of the invention involves adjusting position and size of the intraocular neoplasm in trans-scleral diaphanoscopic way. Rectangular scleral pocket is built above the intraocular neoplasm to 2/3 of sclera thickness with its base turned away from limb. Several electrodes are introduced into intraocular neoplasm structure via the built bed. The electrodes are manufactured from platinum group metal. Electrochemical destruction is carried out with the same current intensity in changing electrodes polarity and their position in the intraocular neoplasm space, and the electrodes are removed. Superficial scleral flat is returned to its place and fixed with interrupted sutures. 0.1-1% aqueous solution of khlorin as photosensitizer, selected from group containing photolon, radachlorine or photoditazine, is intravenously introduced at a dose of 0.8-1.1 mg/kg after having carried out vitrectomy and retinotomy. Visual control of intraocular neoplasm cells fluorescence is carried out by applying fluorescent diagnosis methods. After saturating the intraocular neoplasm with the photosensitizer to maximum saturation level, intravitreous laser radiation is carried out in parallel light beam of wavelength equal to 661-666 nm is applied at a dose of 30-120 J/cm2. The transformed retina and tumor destruction products are intravitreally removed using vitreotome. Boundary-making endolasercoagulation of retinotomy area is carried out after having smoothed and compressed retina with perfluororganic compound. The operation is finished with placing sutures on sclerotomy and conjunctiva. Platinum, iridium or rhodium are used as the platinum group metals. The number of electrodes is equal to 4-8.

EFFECT: reduced risk of metastasizing.

4 cl, 13 dwg

FIELD: medicine.

SUBSTANCE: method involves building tunnel to posterior eyeball pole in inferoexterior and superexterior quadrants. The tunnel is used for implanting flexible polymer magnetolaser implant to the place, the subretinal neovascular membrane is localized. The implant has a permanent magnet shaped as a cut ring and is provided with drug delivery system and a short focus scattering lens of laser radiator connected to light guide. The permanent implant magnet is axially magnetized and produces permanent magnetic field of 5-7 mTesla units intensity. It is arranged with its north pole turned towards sclera at the place of the subretinal neovascular membrane projection with extrascleral arrangement of laser radiator lens membrane being provided in the subretinal neovascular membrane projection area. The other implant end is sutured to sclera 5-6 mm far from the limb via holes made in advance. The implant is covered with conjunctiva and retention sutures are placed thereon. Light guide and drug supply system lead is attached to temple with any known method applied. Drugs are supplied via the implant drug supply system in retrobulbary way in any order. Triombrast is given in the amount of 0,4-0,6 ml and dexamethasone or dexone in the amount of 0,4-0,6 ml during 3-4 days every 12 h. 0.1-1% aqueous solution of khlorin is intravenously introduced at the third-fourth day after setting the implant as photosensitizer, selected from group containing photolon, radachlorine or photoditazine, at a bolus dose of 0.8-1.1 mg/kg. Visual control of subretinal neovascular membrane cells fluorescence is carried out by applying fluorescent diagnosis methods. After saturating the subretinal neovascular membrane with the photosensitizer to maximum saturation level, intravitreous, transretinal laser radiation of 661-666 nm large wavelength is applied at general dose of 30-120 J/cm2. The flexible polymer magnetolaser implant is removed and sutures are placed on conjunctiva. Permanent magnet of the flexible polymer magnetolaser implant is manufactured from samarium-cobalt, samarium-iron-nitrogen or neodymium-iron-boron system material. The photosensitizer is repeatedly intravenously introduced at the same dose in 2-3 days after the first laser radiation treatment. Visual intraocular neoplasm cells fluorescence control is carried out using fluorescent diagnosis techniques. Maximum level of saturation with the photosensitizer being achieved in the subretinal neovascular membrane via laser light guide and implant lens, repeated laser irradiation of the subretinal neovascular membrane is carried out with radiation dose of 30-60 J/cm2.

EFFECT: accelerated subretinal edema and hemorrhages resorption; regression and obliteration of the subretinal neovascular membrane; prolonged vision function stabilization.

6 cl

FIELD: medicine.

SUBSTANCE: method involves administering Noliprelum in postoperative period for reducing left ventricle hypertrophy.

EFFECT: enhanced effectiveness of treatment in early postoperative period.

FIELD: organic chemistry, chemical technology, herbicides.

SUBSTANCE: invention describes a method for preparing compounds of the formula (I):

wherein each R1, R2, R3 means independently of one another (C-C6)-alkyl; R can represent also pyridyl; R4 and R5 in common with nitrogen atoms to which they are joined form unsaturated 5-8-membered heterocyclic ring that can be broken by oxygen atom; G means hydrogen atom. Method involves interaction of compound of the formula (II):

wherein R1, R2 and R3 have above given values; R6 is a group RR9N-; R7 is a group R10R11N-; each among R8, R, R10 and R11 means independently of one another hydrogen atom or (C1-C6)-alkyl in inert organic solvent being optionally with the presence of a base with compound of the formula (IV) ,

(IVa)

or (IVb) ,

wherein R4 and R have above given values; H x Hal means hydrogen halide. The prepared compound of the formula (I) wherein G represents ammonium cation is converted to the corresponding compound of the formula (I) by treatment with Brensted's acid wherein G represents hydrogen atom. Also, invention describes compound of the formula (II) wherein R1, R2, R3, R6 and R7 have above indicated values.

EFFECT: improved preparing method.

9 cl, 12 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to derivatives of benzodiazepine. Invention describes a derivative of benzodiazepine of the formula (I): wherein dotted lines show the possible presence of a double bond; R1, R2, R3, R4 and R5 are given in the invention claim; n represents 0, 1, 2, 3 or 4; X represents sulfur atom (S) or -NT wherein T is give in the invention claim; A represents hydrogen atom, (C6-C18)-aryl group substituted optionally with one or more substitutes Su (as given in the invention claim) or (C1-C12)-alkyl; or in alternative variant R4 and R5 form in common the group -CR6=CR7 wherein CR6 is bound with X and wherein R6 and R7 are given in the invention claim, and their pharmaceutically acceptable salts with acids or bases. It is implied that compounds corresponding to one of points (a)-(e) enumerated in the invention claim are excluded from the invention text. Also, invention describes methods for preparing compounds of the formula (I) and a pharmaceutical composition eliciting the hypolipidemic activity. Invention provides preparing new compounds eliciting the useful biological properties.

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

20 cl, 6 tbl, 192 ex

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