Deemed 4,6-desulfurisation acid as a monomer to obtain a heat-resistant polymers
(57) Abstract:Usage: as a monomer to obtain a heat-resistant polymers. The inventive product - deemed 4,6-desulfurisation acid f-crystals I. BF C8H4O4N2S4exit 96,25% so pl. 218 22°C. Reagent 1: deemed 4,6-desulfosarcina acid. Reagent 2: P2S5. Reaction conditions: reagent ratio 1 (1 2) in the environment of pyridine at boiling point. The structure of f-crystals I: The invention relates to the production of heterocyclic compounds containing two cyclic selftimer grouping in a single aromatic nucleus such as diimide 4,6-Desulfovibrio acid (dithio-m-bisharin), formulas
which can be used as a monomer for the synthesis of new geterotsiklicheskikh heat-resistant polymers, new polymers with a system of conjugate relations, as well as new reactive oligomers.Known deemed 4,6-disulfonate - left acids HNNH on the basis of which to obtain polymers with-SO2- and-CO - groups in imenom cycle [E. P. Melnikov, A. B. Tagiev. Synthesis of polyimides with-SO2- and-CO-groups in imenom cycle. Azerb.chem.W. 1974, No. 2, S. 65]
You know Paul who / Europe. chem. W. 1976, No. 4, S. 46]
However, this monomer has limited solubility in common organic solvents and low reactivity in reactions of polycondensation. The polymers obtained based on it, are low molecular weight and mostly insoluble products.The purpose of the invention, a new monomer having high reactivity and improved solubility.This goal is achieved diimide 4,6-desulfurisation acid as a monomer to obtain a heat-resistant polymer, which is obtained by processing diimide 4,6-desulfosarcina acid pentasulfide phosphorus, taken in a molar ratio of 1:(1-2) in the environment heteroaromatic tertiary amine at the boiling temperature of the reaction mass within 1-3 hoursThe reaction is carried out by addition with stirring of the dry powder pentasulfide phosphorus to a thin suspension of diimide 4,6-desulfosarcina acid in pyridine at 75-80aboutWith gradual increase of temperature up to 110-115aboutWith continued heating at this temperature for 1-3 h, then cooled the reaction mass to room temperature 15-20aboutAnd allocation of target prodnum way in contrast to the known analogue of the two carbonyl (C=0) group is replaced by a thiocarbonyl (C=S) group, it allows you to increase the reactivity and to improve the solubility of the target product.The interaction of diimide 4,6-desulfurisation acid with 4,4"-diaminodiphenyl in the environment of the polar aprotic solvent at a temperature of 60-65aboutWith synthesized polymer with high molecular weight (logand 0.46 DL/g). It is well soluble in polar aprotic solvents and has a heat resistance up to 350aboutC.P R I m e R 1. In a round-bottom three-neck flask with a capacity of 250 ml, equipped with a mechanical stirrer (through the gate), thermometer and reflux condenser, download a thin slurry 5,76 g (0.02 mol) of m-bisharin in 150 ml dry pyridine and the flask placed in an oil bath, the temperature was then raised to 75-80aboutC. With constant stirring to a thin suspension in one step add 9.80 g (0,042 mol) of pentasulfide phosphorus (in the form of finely pulverized dry powder) and continue heating. When 90-95aboutWith the reaction mixture dissolves and turns a dark orange homogeneous solution. Next, the temperature was raised to 110-115aboutWith and with stirring, boil for another 2 hours After cooling to room temperature the reaction mass becomes those who in the song data of the upper layer is separated from the dark brown of the lower layer. From light brown filtrate the solvent is distilled off under reduced pressure (3-4 mm RT.CT.) dry, and dark yellow solid residue is recrystallized from dry ethanol. Fallen light orange crystals are collected, filtered and dried in vacuum at 60-70aboutC to constant weight. The selected substance is a light orange powder product. Output 6,16 g (96,25% of theoretical), so pl. 218-220aboutC.Found, 30,38; N 1,40; N Of 8.47, S 39,55.WITH8H4ABOUT4N2S4.Calculated With 30,02; N 1,26; 8,75 N; S 40,04.In the infrared spectrum has absorption bands at 2980-2840 cm-1(NH), 1480-1440 and 1420 cm-1(C=S), 1390-1360 and 1180-1140 cm-1(SO2-), 1320-1280 cm-1(C-N), which correspond lit. data.P R I m m e R 2. The conditions of the reaction and selection of the target product similar to example 1, but at 110-115aboutWith the stirring is continued for 3 hours Output dithio-m-bisharin is 96% of theoretical so pl. 218-220aboutC.In the infrared spectrum has absorption bands at 2980-2840 cm-1(NH), 1480-1440 and 1420 cm-1(C=S), 1390-1360 and 1180-1140 cm-1(SO2-) 1320-1280 cm-1(C-N).P R I m e R 3. Unlike the 16-219aboutC.In the infrared spectrum has absorption bands at 2980-2840 cm-1(NH), 1480-1440 and 1420 cm-1(C=S), 1320-1280 cm-1(C-N), 1390-1360 and 1180-1140 cm-1(SO2-).P R I m e R 4. Acquisition and allocation of dithio-m-bisharin carried out under conditions analogous to example 1, with the only difference that the pyridine take in 200 ml. Exit 94% of theoretical, so pl. 218-220aboutC. the infrared spectrum has absorption bands at 2980-2840 cm1(NH), 1480-1440 and 1420 cm-1(C=S), 1390-1360 and 1180-1140 cm-1(-SO2-) 1320-1280 cm-1(WITH-N).P R I m e R 5. Conditions of the acquisition and allocation analogously to example 1, the only difference is that the pyridine take in the amount of 100 ml. Output 90% so pl. 218 to 221aboutC.In the infrared spectrum has absorption bands at 2980-2840 cm-1(NH), 1480-1440 and 1420 cm-1(C=S), 1390-1360 and 1180-1140 cm-1(SO2-), 1320-1280 cm-1(C-N).P R I m e R 6. Unlike example 1, pentasulfide phosphorus charge in the amount of 4.90 g (0,021 mol). The yield is 85% of theoretical so pl. 216-218aboutC.In the infrared spectrum has absorption bands at 2980-2840 cm-1(NH), 1480-1440 and 1420 cm-1(C=S), 1390-1360 and 1180-1140 cm-1(SO2-), 1320-1280 cm-1(C-N).P R I m e R 7. the ndimethylacetamide (DMAA) with vigorous stirring once added 1.20 g of (3.75 mmole) dithio-m-bisharin (tankomaster powder). Get a homogeneous solution was yellowish-orange color, which persists for 20 min stirring at 18-20aboutC. Then the reaction mass is painted in a light brown color. Next, the temperature of the reaction mass was raised to 60-65aboutWith and continue stirring for 2 hours By the end of the experience obtained viscous solution turns brown, it is cooled to 18-20aboutC and poured into 400 ml of water. The reaction product precipitated as a dark yellow powder, which is collected, filtered, washed with water and dried in vacuum at 60-70aboutC to constant weight. The resulting substance is a yellowish brown solid product. Output -1,15 g (96% of theoretical).logand 0.46 DL/g (0.5 g of polymer in 100 ml of DMAA in the 30aboutC). According to TGA, thermal degradation of the polymer in air begins at 350aboutC.Found, With 54,48; N. Of 2.54; N, 14.24 From; S 15,18.[ C20H12O4N4S2n< / BR>Calculated With 55,04; N 2,77; N 14,66; S 14,60.In the infrared spectrum has absorption bands at 1645-1625 cm-1(C=N), 3000-2800 cm-1(NH), 1340-1300 and 1180-1150 cm-1(SO2-) that correspond lit.data.The monomer (dithio-m-bisharin) obtained above OPI high reactivity, due to the substitution of two carbonyl (C=O) groups on more mobile thiocarbonyl (C=S) group;
improved solubility, due to the disappearance of hydrogen bonds, as in contrast to the carbonyl (C=O) groups, thiocarbonyl (C=S) group does not form hydrogen bonds with the NH-group;
low melting point (so pl. 218-220aboutFor dithio-m-bisharin, and for Matricaria so pl. 410aboutC) due to the disappearance of hydrogen bonds;
the polymer obtained on its basis is a high molecular weight (logand 0.46 DL/g), has a high solubility in polar aprotic solvents and heat resistance up to 350aboutCompared to the low molecular weight (logof 0.2 DL/g) and insoluble polymers derived from m-bisharin. < / BR>as the monomer for heat-resistant polymers.
FIELD: organic chemistry, medicine, pharmacy.
SUBSTANCE: invention relates to novel soluble pharmaceutical salts formed from salt-forming active compound of the general formula (I) or (II) and sugar substitute that can be used in preparing medicinal agents useful in pain and enuresis treatment. Salt-forming active substance represents a salt-forming compound among 1-phenyl-3-dimethylaminopropane compounds of the general formula (I) wherein X means -OH, F, Cl, H or group -OCOR6; R1 represents (C1-C4)-alkyl group; R2 represents H or (C1-C4)-alkyl group; R3 represents H or (C1-C4)-alkyl group with a direct chain, or R2 and R3 form in common (C4-C7)-cycloalkyl group and if R5 means H then R4 represents group O-Z in meta-position wherein Z means H,(C1-C3)-alkyl, -PO-(O-C1-C4-alkyl)2, -CO-(O-C1-C5-alkyl), -CONH-C6H4-(C1-C3-alkyl), -CO-C6H4-R7 wherein R7 represents -OCO-C1-C3-alkyl in ortho-position or group -CH2N(R8)2 in meta- or para-position and wherein R8 means (C1-C4)-alkyl or 4-morpholino-group, either R4 represents S-(C1-C3)-alkyl in meta-position, meta-Cl, meta-F, group -CR9R10R11 in meta-position wherein R9, R10 and R11 mean H or F, group -OH in ortho-position, O-(C2-C3)-alkyl in ortho-position, para-F or group -CR9R10R11 in para-position wherein R9, R10 and R11 mean H or F, or if R5 means Cl, F, group -OH or O-C1-C3-alkyl in para-position then R4 means Cl, F, group -OH or O-(C1-C3)-alkyl in meta-position, or R4 and R5 form in common group 3,4-OCH=CH- or OCH=CHO-; R6 means (C1-C3)-alkyl, or salt-forming active substance represents a salt-forming compound among 6-dimethylaminomethyl-1-phenylcyclohexane compounds of the general formula (II) wherein R1' represents H, -OH, Cl or F; R2' and R3' have similar or different values and represent H, (C1-C4)-alkyl, benzyl, -CF3, -OH, -OCH2-C6H5, O-(C1-C4)-alkyl, Cl or F under condition that at least one among radicals R2' either R3' means H; R4' represents H, -CH3, -PO-(O-C1-C4-alkyl)2, -CO-(O-C1-C5-alkyl, -CO-NH-C6H4-(C1-C3)-alkyl, -CO-C6H4-R5', CO-(C1-C5)-alkyl), -CO-CHR6'-NHR7' or unsubstituted either substituted pyridyl, thienyl, thiazolyl or phenyl group; R5' represents -OC(O)-(C1-C3)-alkyl in ortho-position or -CH2N(R8')2 in meta- or para-position and wherein R8' means (C1-C4)-alkyl, or both radicals R8' in common with nitrogen atom (N) form 4-morpholino-group, and R6' and R7' have similar or different values and represent H or (C1-C6)-alkyl under condition that if both radicals R2' and R3' represent H then R4' doesn't mean -CH3 when R1' represents additionally H, -OH or Cl, either R4' doesn't mean H when R1' represents additionally -OH. Also, invention relates to a medicinal agent based on indicated salts.
EFFECT: valuable medicinal properties of salts and drug.
14 cl, 1 tbl, 8 ex
SUBSTANCE: invention relates to novel derivatives of diaryl compounds with formulae given below ,
, in which M is S(O)2, Rx represents alkyl, R1, R2, R3 and R4 are each independently selected from OH and -NR7S(O)2R8, R5 and R7 each independently represents hydrogen or alkyl, R8 is alkyl; and their pharmaceutically acceptable derivatives, as well as to pharmaceutical compositions containing said compounds and their use in making a medicinal agent with inhibitory activity on Aβ, IAPP amyloid fibrils or synuclein fibrils.
EFFECT: substituted n-arylbenzamide and related compounds for treating amyloid diseases and synucleinopathy are disclosed.
11 cl, 19 ex, 6 tbl
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention relates to novel compounds, which possess qualities to estrogen modulators, of general formula (1) or its pharmaceutically acceptable salt, where R1 represents hydrogen atom or (C1-C6)alkyl, -SO2NR7R8, phenyl (C1-C3)alkyl or (C1-C3)alkyl, substituted with 5-8-member heterocyclic radical, containing nitrogen atom; R2 and R3 each independently represents hydrogen atom or hydroxyl, halogen atom or (C1-C6)alkoxy; X represents O, S, SO, SO2 or NR4; R4 represents hydrogen atom or (C1-C6)alkyl, phenyl, phenyl(C1-C3)alkyl, (C1-C3)alkyl, substituted with 5-8-member saturated heterocyclic radical, containing one nitrogen atom, or group -COR7, -CO2R7 or -SO2NR7R8, where phenyl is not substituted or is substituted with at least one substituent, selected from group which includes hydroxyl, halogen atom or phenyl(C1-C3)alkoxy; Y represents direct bond, -(CR10R11)n- or -R10C=CR11-; R7 and R8 each independently represents hydrogen atom or (C1-C6)alkyl group; R10 and R11 each independently represent hydrogen atom or cyano, or group CONR7R8; n equals 1 or 2; A represents (C3-C12)cycloalkyl or phenyl, where phenyl is not substituted or is substituted with at least one substituent, selected from group which includes hydroxyl, halogen atom, (C1-C3)alkyl, (C1-C3)alkoxy; when X represents NR4, Y and R2 together with containing them indazole cycle can also form 1H-pyrano[4,3,2-cd)indazole; on condition that: 1) when X represents O, S or NR4, R1 represents hydrogen atom or (C1-C6)alkyl, and Y stands for direct bond, then A is not optionally substituted phenyl; 2) when X represents O, R1O represents 6-OH or 6-OCH3, Y represents direct bond and A represents cyclopeptyl, then (R2, R3) or (R3, R2) are different from (H, CI) in position 4, 5; 3) when X stands for O, R1O represents 6-OH, R2 and R3 represent H, and Y represents CH=CH, then A is not phenyl or methoxyphenyl; 4) when X represents SO2, A represents phenyl and R1O represents 5-or 6-OCH3, then (R2, R3) or (R3, R2) are different from (H, OCH3) in position 6- or 5-, compound not being one of the following: 3-phenyl-5-(phenylmethoxy)-1H-indazole; n-hydroxy-3-phenylmethyl-7-(n-propyl)-benz[4,5]isoxazole; 3-(4-chlorphenylmethyl)-6-hydroxy-7-(n-propyl)-benz[4,5]isoxazole; 6-hydroxy-3-(2-phenylethyl)-7(n-propyl)-benz[4,5]isoxazole; 3-cyclopropyl-6-hydroxy-3-phenylmethyl-7-(n-propyl)-benz[4,5|isoxazole; 3-cyclohexylmethyl-6-hydroxy-3-phenylmethyl-7-propyl-benz[4,5]isoxazole. Invention also relates to pharmaceutical composition, application and method of prevention and treatment of disease, where modulation of estrogen receptors is required.
EFFECT: obtaining novel compounds, which possess qualities of estrogen receptors modulators.
18 cl, 7 dwg, 8 tbl, 97 ex
SUBSTANCE: invention relates to bicyclosulphonyl acid (BCSA) compounds of formula: where: where each of -Rpw, -Rpx, -RPY, and -RPZ independently denotes H or -RRS1; each -RRS1 independently denotes -F, -Cl, -Br, -I, -RA1, -CF3, -OH, -OCF3 or -ORA1; where each RA1 independently denotes C1-4alkyl, phenyl or benzyl; and additionally, two neighbouring -RRS1 groups can together form -OCH2O-, -OCH2CH2O- or -OCH2CH2CH2O-; -RAK independently denotes a covalent bond, -(CH2)- or -(CH2)2-; -RN independently denotes -RNNN, or -LN-RNNN; the rest of the values of the radicals are given in claim 1, which act as inhibitors of inhibitors of tumor necrosis factor-α converting enzyme (TACE).
EFFECT: compounds are useful in treating TNF-α mediated conditions.
36 cl, 303 ex
SUBSTANCE: invention relates to benzothiazine derivatives represented by general formula (I): 0, where R1 is a hydrogen atom; C1-C6 alkyl; COR5; SO2R5; CO(CH2)mOR6; (CH2)mR6; (CH2)mCONR7R8; (CH2)nNR7R8; (CH2)nOR6; CHR7OR9; (CH2)mR10; m assumes values from 1 to 6; n assumes values from 2 to 6; R2 is phenyl; naphthyl, 1,2,3,4-tetrahydro-naphthalene, biphenyl, phenylpyridine or a benzene ring condensed with a saturated or unsaturated monocyclic heterocycle containing 5-7 atoms and consisting of carbon atoms and 1-4 heteroatoms selected from N, O or S, other than indole, R3 is methyl or ethyl; R4 and R′4 are identical or different and denote a hydrogen atom; a halogen atom; C1-C6 alkyl; NR7R8; SO2Me; as well as stereoisomers, salts and solvates thereof, for therapeutic use and which are capable of inhibiting 11β-HSD1 on an enzymatic and cellular level.
EFFECT: obtaining benzothiazine derivatives.
17 cl, 197 ex
SUBSTANCE: invention refers to a compound of formula 1, where R2 represents hydrogen or dimethylaminogroup; R3 represents hydrogen; R4 represents C3-10-cycloalkyl optionally substituted by C1-6-alkyl, or benzyl optionally substituted by halogen; or R3 and R4 together with nitrogen atom, to which they are attached, form piperidinyl substituted by one or more substitutes independently specified in a group consisting of hydroxyl or phenyl optionally substituted by halogen; R5 represents C1-6-alkyl or benzyl optionally substituted by halogen; R6 represents benzodioxolyl or phenyl optionally substituted by 1-3 substitutes independently specified in a group consisting of halogen, hydroxyl, C1-6-alkoxygroup optionally substituted by halogen, C1-6-alkyl, phenoxygroup optionally substituted by halogen, cyanogroup or C1-6-alkyl, and phenyl optionally substituted by C1-6-alkyl or halogen, or its pharmaceutically acceptable salt. The compound of formula 1 is applicable for producing a composition or a medicinal product for treating or controlling cell proliferative disorders.
EFFECT: sultam derivatives showing cytotoxic activity.
40 cl, 38 ex