The method of producing sidaction
(57) Abstract:The invention relates to the synthesis of biologically active substances, in particular to the synthesis of ecdysteroids, specifically to the synthesis of SIDACTION found in very small amounts in some species, for example Blehnum niponicum and Vitex canescens. The method is realized by the interaction of the 20-hydroxyecdysone (1) c triperoxonane anhydride. Under the action of a suspension of the compound (1) in chloroform three times molar excess of the reagent, after 30 min was observed homogenization of the reaction mixture, after evaporation of which the chromatography was carried out was selected SIDACTION with the release of 42%. The method is simple to perform and gives a higher yield of the target product. The invention relates to the synthesis of biologically active substances, in particular to the synthesis of ecdysteroids, specifically to the synthesis of SIDACTION found in very small amounts in some species, for example Blehnum niponicum [Takemoto, T. Okuyama, S. Arihara, Y. and H. Hikino Hikino. Chem. Pharm. Bull., 1969, 17, 1973] and Vitex canescens [A. Suksamrarn, N. Promrangsan, Century Chitkul, S. Homvisasevonsa and A. Sirikate. Ecdysteroids of the root bark of Vitex caescens. // Phytochemistry, 1997, 45, 6 1149-1152].Ecdysteroids are widely distributed in the animal and vegetable world and perform the function regulator analogues are of interest to medicine. Recently in this regard, there is a considerable interest derived ecdysteroids with a heterocycle in a side chain, some of which are expected, in particular, antitumor activity. Know about getting SIDACTION semisodium synthesis (22,25-anhydrous-20-hydroxyecdysone) [Roussel P. G., Turner N. J., Dinan L. N. Synthesis of Shidasterone and the Unambiguous Determination of its Configuration at C-22//J. Chem. Soc. , Chem. Commun. , 1995, 933-934.] 20-hydroxyecdysone. When interacting 20-hydroxyecdysone 1 with phenylboric acid in a medium of dimethylformamide (DMF) was obtained 20,22-phenylboronate-20-hydroxyecdysone 2. In the interaction of compound 2 with acetone in the presence of 2,2-dimethoxypropane (DMP) and TsOH was obtained 2,3-acetonide-20,22-phenylboronate-20-hydroxyecdysone 3. Treatment of compound 3 in a 30% solution of hydrogen peroxide in the alkaline environment of tetrahydrofuran led to selective removal boronates protection with obtaining 2,3-monoacetate 4, the total output of which amounted to 65%. Interaction acetonide 4 methylchloride in the presence of (i-Pr)2NEt in dichloromethane was obtained (22/R)-mesilate 5 (50%). Under the action of dry KF or anhydrous acetonitrile (tetrabutylammonium fluoride (F)) in THF mesilate 5 was converted into 20R,22S-epoxide 6 (50%). Effect on connection 6 targetrate of triethylamine n is from 8 to exit 91%, identical to natural object (scheme 1).The disadvantages of this synthesis is a multi-stage, the use of specific reagents, incomplete conversion of the starting reagents at each stage, which requires additional separation, the low yield of the final product (about 10%).The aim of the invention is to simplify the way with a simultaneous increase in the yield of the final product.A distinctive feature of the proposed method, which allows to solve tasks, is the use of triperoxonane anhydride (TFW) as a dehydrating agent. When studying the interaction of 20-hydroxyecdysone (1) with TFW we found that under the action of a suspension of compound 1 in chloroform three times molar excess of the reagent after 30 min was observed homogenization of the reaction mixture, after evaporation of which the chromatography was carried out was allocated 22,25-anhydrous-20-hydroxyecdysone (8) with the release of 42%, identical (IR, UV, NMR1H and13(C) SIDACTION obtained in the above-mentioned 7-stage synthesis [Roussel P. O., V. Sik, Turner N. J. and Dinan L. N. Synthesis and biological activity of side-chain analogues of ecdysone and 20-hydroxyecdysone//J. Chem. Soc., Perkin Trans. 1, 1997, 2237].Bore which opens the way to the final product and provides a higher yield of the final product (42%) in comparison with the known.The synthesis is carried out as follows.An example of the method. A mixture of 0.53 g (2.49 mmol) of TFW and 0.4 g (0.83 mmol) of 1 in 5 ml SNS3(scheme 2) stirred 30 min at room temperature (up to homogenization of the reaction mixture). The reaction mass was evaporated, the residue was chromatographically on a column with SiO2(eluent l3-Meon, 5:1) with 0.17 g of SIDACTION (22,25-anhydrous-20-hydroxyecdysone but also or (20R, 22R)-22,25-anhydrous-2, 3, 14, 20 tetrahydroxy-5-cholesterol-7-EN-6-she (8)). The method of producing SIDACTION of 20-hydroxyecdysone but also characterized in that 20-hydroxyecdysone is subjected to interaction with triperoxonane anhydride, taken in a 3-molar excess in the environment of chloroform at room temperature for 30 minutes
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FIELD: organic chemistry, medicine, pharmacy.
SUBSTANCE: invention relates to the substituted 4-benzylaminoquinolines and their heteroanalogs of the general formula (I): P-L-G (I) wherein G means compound of the formula: G(I) wherein K means -OR(7), -NH-CH2-CH2-SO3H, -NH-CH2-CO2H wherein R(7) means hydrogen atom, CH3; R1-R6 mean independently of one another hydrogen atom, -OR(10), -R(10) being one of residues R1-R6 means a bond with L always; R(10) means hydrogen atom, (C1-C4)-alkyl; L means (C1-C15)-alkyl being one or some structural CH2-fragments can be replaced for -C≡C-, -NR(11)-, -CO-, -O- wherein R(11) means hydrogen atom; P means: or wherein A means nitrogen atom (N); B means CH; D means CH; E means CH; R16-R24 mean independently of one another hydrogen atom, F, Cl atoms, (C1-C4)-alkyl being alkyl residues can be mono- or multiple-substituted with fluorine atom, NR(25)R(26), OR(25), COR(25), COOR(25), CONR(25)R(26) being one of residues R16-R(24) means a bond with L always; R25 and R26 mean independently of one another hydrogen atom, (C1-C4)-alkyl or benzyl. Also, invention relates to their pharmaceutically acceptable salts. Also, invention relates to a method for their preparing and to a drug based on thereof for prophylaxis of supersaturation of bile with cholesterol. Invention provides preparing new compounds and a drug based on thereof that can be used for prophylaxis and treatment of patients suffering with gallstones.
EFFECT: improved preparing method, valuable medicinal properties of compounds and drugs.
10 cl, 32 ex
FIELD: medicine, endocrinology, pharmacy.
SUBSTANCE: invention relates to a pharmaceutical composition comprising drospirenone as the first active agent in the amount corresponding to daily dose from 2 to 4 mg in administration of the composition, and ethynylestradiol as the second active agent in the amount corresponding to daily dose from 0.01 to 0.05 mg in combination with one or some pharmaceutically acceptable vehicles or additives. Drospirenone as a component of the pharmaceutical composition is in the finely divided form. The preparation comprises some separately packages and individually taken medicinal units placed in the unit package and designated for oral administration for at least 21 days at a time and indicated daily medicinal units comprise the combination of drospirenone and ethynylestradiol. The preparation can comprise 7 and less daily doses no containing any active agent or containing ethynylestradiol only. The combination of ethynylestradiol and drospirenone provides the safety contraceptive activity due to using the maximal dose of drospirenone being without adverse effects, in particular, excessive diuresis.
EFFECT: improved and valuable properties of combination.
34 cl, 5 dwg, 5 ex
SUBSTANCE: method involves carrying out laparoscopy and administering Danazol at a dose of 400 mg twice a day for 6 months. Danazol treatment being over and normal prolactinemia being observed in biphasic menstrual cycle, Parlodel is administered at a dose of 2.5 mg twice a day for three menstrual cycles long period.
EFFECT: enhanced effectiveness in normalizing hormone background and pregnancy taking place.
FIELD: pharmaceutical industry, medicine.
SUBSTANCE: method relates to composition containing estrogen as the first active ingredient in amount sufficient to treatment of diseases, disorders, and symptoms associated with deficit of endogen estrogen levels in women; and drospyrenon as the second ingredient in amount sufficient to endometrium protection from unfavorable estrogen effects. Methods for treatment also are disclosed. Preparations of present invention are useful in combination therapy for continuous, subsequent or intermittent administration.
EFFECT: method for replacement hormonotherapy in women of improved efficiency.
46 cl, 7 ex
FIELD: organic chemistry, steroids, biology.
SUBSTANCE: invention relates to steroid compounds of the general formula (X):
wherein in fragment of the formula XA:
each bond between C6 and C7, between C7 and C8, between C8 and C9, between C8 and C14 and between C14 and C15 is a single or double bond under condition that each atom C6, C7, C8, C9, C14 and C15 is bound with adjacent C-atom by a single bond or one double bond; CR3 means -CHOH; A means methylene or ethylene group; R4 and R4' mean (C1-C4)-alkyl, hydrogen atom (H); R20 means (C1-C4)-alkyl; R23 and R23' mean in common piperidine-1-yl, morpholine-4-yl, pyrrolidine-1-yl, piperazinyl possibly substituted with -OH, benzene, pyridine, pyrimidine, phenyl, alkoxycarbonyl group, or R23 means H and R23' means substituted alkyl. These compounds can be used for stimulation of meiosis in human oocytes. In proposed compounds steroid differs specifically as nitrogen atom of amino-group is bound with C17-atom of steroid skeleton by spacer A.
EFFECT: improved methods of synthesis, valuable biological properties of compounds.
16 cl, 8 dwg, 2 tbl, 30 ex
FIELD: organic chemistry, steroids, medicine, pharmacy.
SUBSTANCE: invention describes compounds of the formula (I) , their pharmaceutically acceptable salts, solvates, stereoisomers wherein in each case R1 and R2 mean independently hydrogen atom, possibly substituted alkyl, aryl, heteroalkyl wherein heteroatom means nitrogen atom, heteroaryl wherein a heteroatom means nitrogen, oxygen or sulfur atom; or R1 and R2 in common with N-atom to which they are bound can form a heterocyclic structure as a moiety of organic group comprising 6-12 carbon atoms and comprising optionally 1-6 heteroatoms chosen from nitrogen and oxygen atoms; R3 and R4 mean hydrogen atom or a protective group under condition that R and/or R4 represents part of the hydroxyl protective group; № from 1 to 17 mean carbon atoms wherein C-atoms at № 1, 2, 4, 11, 12, 15 and 16 can be substituted with two from R5 groups; C17-atom can be substituted with one of the following groups: =C(R5)(R5), =C=C(R5)(R5) or two from groups - R5 and -OR6; C-atoms at № 5, 8, 9, 10, 13 and 14 can be substituted with group R5 wherein R means hydrogen atom (H), (C1-C6)-alkyl, (C1-C6)-hydroxyalkyl, (C1-C6)-halogenalkyl; R6 means H, protective group, such as -OR6-protected OH-group wherein the group -OR6 can form cyclic protective structure for vicinal -OH groups. Proposed compounds can be components of pharmaceutical composition and useful in treatment and/or prophylaxis of different states including inflammation, asthma, allergic disease, chronic obstructive pulmonary disease, allergic dermatitis, solid neoplasms, ischemia and cardiac arrhythmia.
EFFECT: improved treatment method, valuable medicinal properties of substances and pharmaceutical composition.
53 cl, 10 tbl, 24 ex
FIELD: organic chemistry, steroids, medicine, pharmacy.
SUBSTANCE: invention describes novel halogen- and pseudohalogen-substituted 17-methylene-4-azasteroids of the general formula (I) wherein each R20 and R20a means independently fluorine, chlorine, bromine atom, (C1-C4)-alkyl, hydrogen atom (H), cyano-group; R4 and R10 mean hydrogen atom or methyl group; both R1 and R2 represent hydrogen atom and form an additional bond. Compounds are inhibitors of 5α-reductase and can be used in treatment of diseases caused by the enhanced blood and tissue testosterone and dihydrotestosterone level.
EFFECT: valuable medicinal and biochemical properties of compounds.
9 cl, 5 dwg, 1 tbl, 10 ex
SUBSTANCE: method involves applying Sarsasapogenin in combination with one or several compounds taken from group consisting of Smilagen and Anzurogenin-D, for preparing composition for treating Parkinson disease or for treating postural hypotension, autism, chronic fatigue syndrome, heavy myasthenia gravis, Lambert-Eaton disease, Gulf War Syndrome and syndrome caused by professional contact with organophosphorous compounds. Sarsasapogenin selectively increases muscarinic receptors M1 activity, contributing to stimulating synaptic transmission, without М2 receptors activity being influenced (which evoke negative feedback and muscarinic transmission interruption).
EFFECT: enhanced effectiveness of treatment.
3 cl, 8 tbl
FIELD: medicine, chemical-technological industry.
SUBSTANCE: the present innovation deals with applying the antagonist of glucocorticoid receptor (11β,17β)-11-(1,3-benzodioxol-5-il)-17-hydroxy-17-(1-propynyl)estra-4,9-dien-3-on (Org 34517) for obtaining a medicinal preparation in the form applied for peroral intake for treating patients suffering with considerable depressive disorder and, also, the corresponding method of therapy. The suggested Org 34517 initiated quicker onset of antidepressive action against paroxetin.
EFFECT: higher efficiency of application.
6 cl, 3 dwg, 1 ex
FIELD: organic chemistry, steroids.
SUBSTANCE: invention discloses derivatives of steroid sapogenins of the general formula (I): wherein R means alkylcarbonyl, alkoxycarbonyl substituted possibly with amino-group and others under condition that R is not acetyl and R is not ethoxycarbonyl if C3 is in S and C25 in R-configurations simultaneously; R is nor succinyl if C3 and C25 are in S-configuration simultaneously, or C3 R(α) or S(β), and C25 in R-configuration. Also, invention discloses using these compounds in treatment of cognitive dysfunction, noncognitive neurodegeneration, noncognitive neuromuscular degeneration and loss of receptors in absence of cognitive, nervous and neuromuscular insufficiency. Also, invention discloses methods for synthesis of these compounds, treatment and pharmaceutical composition containing thereof.
EFFECT: improved method of synthesis, valuable medicinal properties of compounds and pharmaceutical compositions.
30 cl, 2 tbl, 5 dwg, 16 ex
FIELD: organic chemistry, natural compounds, medicine.
SUBSTANCE: invention describes a glycoside derivative of 4-methylergost-7-ene-3-ol of the formula (I): , method for its preparing and composition for correction of hyperglycemia. The composition represents extract from plant of Liliaceae family, preferably, from Aloe vera. Also, invention describes a medicinal agent used for correction of hyperglycemia, foodstuffs and beverages.
EFFECT: valuable medicinal and nutrient properties of derivative and composition.
14 cl, 2 tbl, 4 dwg, 8 ex