Crystalline 3-cyan-2-morpholino-5-(pyrid-4-yl)-pyridine with a bulk density between 220-360 g/l
(57) Abstract:The inventive crystalline 3-cyan-2-morpholino-5-(pyrid-4-yl)-pyridine F.-ly (I) with a bulk density of 220 - 360 g/l table 4. The structure of f-crystals 1:
The invention relates to a compact, crystalline 3-cyan - 2-morpholino-5-(pyrid-4-yl)-pyridine with high apparent (bulk) density and the method of its production. 3-Cyan-2-morpholino-5-(pyrid-4-yl)-pyridine can be used as a cardiotonic means simultaneously with vasodilator properties.Known to produce 3-cyan-2-morpholino-5-(pyrid-4-yl)-pyridine by reacting 3-cyan-2-chloro-5-(pyrid-4-yl)- pyridine with an excess amount of research and recrystallization of the crude product from ethanol [1,2] While the recrystallized product precipitates in the form of a thin, "stringy" needles, which have only a small apparent density of 150 g/l and creating galenical significant processing difficulties.Therefore there is an urgent need in a compact, crystalline 3-cyan-2-morpholino-5-(pyrid-4-yl)-Piri dine with high apparent density and in a manner that allows it to receive.The basis of the invention p is high apparent density and how it is received.This is because 3-cyan-2-morpholino-5-(pyrid-4-yl)-pyridine or:
a) is dissolved in acid and the obtained solution it is precipitated by using reason, either:
b) is dissolved in the chlorohydrocarbons and precipitated from its solution by adding aliphatic hydrocarbons, either:
b) recrystallized from aliphatic esters of carboxylic acids.You can use 3-cyan-2-morpholino-5-(pyrid-4-yl)-pyridine in the form of the crude product and purified condition.A special variant of the invention consists in the fact that the solutions of 3-cyan-2-morpholino-5-(pyrid-4-yl)-pyridine before precipitation or crystallization is subjected to treatment with adsorbents as activated carbon or silica gel, which especially has the advantage of using the crude 3-cyan-2-morpholino-5-(pyrid-4-yl)-pyridine.If 3-cyan-2-morpholino-5-(pyrid-4-yl)-pyridine need to besiege of its acidic solutions using bases, respectively, of the present invention, it is preferable to carry it out at temperatures 15-40aboutWith, preferably, however, at the 30aboutC.For implementing the method according to the variant: a) suitable Neorganicheskie is full of metals, solutions of ammonia or a solution of carbonates of alkali metals.A special variant of the invention, in the case of the method according to variant a) is that of solutions of 3-cyan-2-morpholino-5-(pyrid-4-yl)-pyridine in inorganic acids by adding another inorganic acid, is separated, dissolved in water and, if necessary, after treatment with adsorbents precipitated with reason.If 3-cyan-2-morpholino-5-(pyrid-4-yl)-pyridine need to besiege of chlorinated hydrocarbons with aliphatic hydrocarbons by way of option b), then for this purpose, suitable as a chlorinated hydrocarbon, e.g. chloroform or dichloromethane, at the same time as aliphatic hydrocarbons are preferably used with any of 5-10 C-atoms, or mixtures thereof, for example, hexane or petroleum ether.If 3-cyan-2-morpholino-5-(pyrid-4-yl)-pyridine according to the method according to option b), you need to be recrystallized, the particular variant embodiment of the invention is that the deposition is carried out by rapid and intensive cooling, especially when mixing. As aliphatic esters of carboxylic acids suitable pH is mi with one to four carbon atoms, preferably butyl acetate.Obtained accordingly to the method of the present invention is compact, crystalline 3-cyan-2-morpholino-5-(pyrid-4-yl)-pyridine, depending on the selected reaction conditions, precipitates three, still unknown crystal modifications, which are here referred to as-and-form.While none of the three modifications cannot be included in the methods a), b) or C). Moreover, even minor changes in these mentioned methods, such as replacement of the acid and/or base option a), or the replacement of chlorinated hydrocarbon and/or an aliphatic hydrocarbon in option b), or even changes during cooling and crystallization rate lead to the occurrence of different crystalline modifications or mixtures thereof.It is important that whatever is received, according to the invention, the crystalline modifications, or their mixtures, it is always possible to obtain a compact crystalline 3-cyano-2-morpholino-5-(pyrid-4-yl)-pyridine high in comparison with the prior art bulk density of about 220-360 g/l, which in combination with pharmaceutical carriers and excipients are well and high quality processed into pharmaceuti forms, such as, for example, tablets or pills, as this can be ensured by a large number of biologically active substances in these solid forms.When a certain quantity per tablet or per core drops can significantly increase the amount of active substance due to the higher bulk density of the latter.In table. 1-4 describes important to identify data, and modification of 3-cyan-2-morpholino-5-(pyrid-4-yl)-pyridine.In table. 1 presents some of the studies of x-ray diffraction data for crystals and modifications to this connection.Below shows the molecule 1 with atom numbering scheme:
< / BR>Table. 2 and 3 contain the coordinates of the atoms 1 and 1-.In table. 4 presents calculated from the data of a single crystal powder chart values and relative intensity) 1 - 1- , as well as some using the Guinier method experimental powder chart 1-.P R I m e R 1. a) 3-Cyan-2-morpholino-5-(pyrid-4-yl)-pyridine - hydrochloride-monohydrate.5,0 kg 3-cyan-2-morpholino-5-(pyrid-4-yl)-pyridine is mixed with 25 l of water and 2.0 l technical hydrochloric acid and heated to approximately the 50aboutC. To the yellow solution on the 20aboutC. Centrifuged and washed with a mixture of 5.4 liters of water and 0.6 l of hydrochloric acid.Output: 5.3 kg (88% of theory).b) 3-cyan-2-morpholino-5-(pyrid-4-yl)-pyridine ( -option).5,3 kg 3-cyan-2-morpholino-5-(pyrid-4-yl)-pyridine-hydrochloride-monohydrate are suspended in 40 l of water, the suspension is heated to 50aboutWith add 0.5 kg of activated charcoal, after stirring for 15 min sucked off and washed with water. The filtrate is cooled to 30aboutC and under stirring for one hour at this temperature, poured about 2.7 l of concentrated solution of hydroxyl sodium until pH 8-9. Centrifuged and washed in the whole 30 l of water.Output: 4.1 kg (93,2% of theory).So pl. 126-128aboutC.The apparent density of the crushed in a mortar samples: approximately 360 g/lP R I m m e R 2. 3-Cyan-2-morpholino-5-(pyrid-4-yl)-pyridine ( -option).1 g of purified 3-cyan-2-morpholino-5-(pyrid-4-yl)-pyridine any modification dissolved in 4 ml 1A HCl by heating at about 50aboutC and under stirring at 30-40aboutWith precipitated by mixing with about 4 ml 1A NaOH. Sucked off, washed with water and dried at 110aboutC.Yield: 0.95 g (95% of theory>P R I m e R 3. 3-Cyan-2-morpholino-5-(pyrid-4-yl)-pyridine ( -option).4.0 kg pre-purified 3-cyan-2-morpholino-5-(pyrid-4-yl)-pyridine are suspended in 40 l of water and add 5.5 kg of lactic acid. Heated to 50aboutWith add 0.2 kg of activated charcoal and after stirring for 15 minutes and filtered. Washed with warm water, cooled to 30aboutWith and added dropwise to about 1.25 l of concentrated sodium hydroxide solution until pH 8-9. Stirred for further 1 h, centrifuged, washed in General, 30 l of water and dried.Output: 3,74 kg (93,5% of theory), slightly yellowish crystals.So pl. 127-129aboutC. the Apparent density of the crushed in a mortar samples: approximately 230 g/lP R I m e R 4. 3-Cyan-2-morpholino-5-(pyrid-4-yl)-pyridine ( and modifications).100 g of pre-purified 3-cyan-2-morpholino-5-(pyrid-4-yl)-pyridine are suspended in 1.2 l of water, add 39 ml technical hydrochloric acid and 5 g of activated charcoal. Heated to 50aboutC and filtered. To the filtrate was added dropwise 26 ml of concentrated ammonia solution at about 30aboutC, stirred for further 1 h, sucked off and washed 6 times with 50 ml water.Output: 96,2 g 00 g/L.P R I m e R 5. 3-Cyan-2-morpholino-5-(pyrid-4-yl)-pyridine ( -option).3 g of purified 3-cyan-2-morpholino-5-(pyrid-4-yl)-pyridine any modification dissolved in 5 ml SIST3with light heating and under stirring precipitated by mixing with 10 ml of hexane. Sucked off and dried.Output: 2,82 g (94% of theory).So pl. 127-128aboutC. the Apparent density of the pulverized with stupke samples: approximately 230 g/lP R I m e R 6. 3-Cyan-2-morpholino-5-(pyrid-4-yl)-pyridine (-option).1 g of purified 3-cyan-2-morpholino-5-(pyrid-4-yl)-pyridine any modification when heated, dissolved in 4 ml of CH2CL2and under stirring precipitated by mixing with 5 ml of hexane. Sucked off and dried.Yield: 0.97 g (97% of theory).So pl. (124) 127-130aboutC. the Apparent density of the crushed in a mortar samples: about 220 g/lP R I m e R 7. 3-cyan-2-morpholino-5-(pyrid-4-yl)-pyridine (a mixture of - and-modification).125 g of the crude product 3-cyan-2-morpholino-5-(pyrid-4-yl)-pyridine with 1 l of butyl acetate is refluxed until dissolution. Filter the hot solution, when heated, stirred for 10 min with 10 g of activated charcoal. Suck goracinova dissolved in 900 ml of butyl acetate when heated, treated with 7 g of activated charcoal, filtered and heated to approximately 70aboutWith the solution with vigorous stirring and cooling is brought to crystallization. Then further stirred for 2 hours at room temperature, left to stand overnight in the refrigerator, sucked off, washed with methanol and dried at 110aboutC.Output: 80 g (67% of theory).So pl. (124) 128-130aboutC.Apparent density pounded in a mortar samples: approximately 245 g/L.By concentrating the mother liquor and recrystallization of the resulting product in the manner described it is possible to increase the output.P R I m e R 8. 3-Cyan-2-morpholino-5-(pyrid-4-yl)-pyridine (a mixture of - and-modifications).The example is carried out analogously to example 5, however, the deposition is carried out by addition of 60 ml of 45% potassium carbonate solution at 30aboutC.Output: 46.6 g (93.2% of theory).So pl. 121-123aboutand 126-128aboutC.Apparent density pounded in a mortar samples approximately 330 g/L. Crystalline 3-cyan-2-morpholino-5-(pyrid-4-yl)-pyridine of the formula
< / BR>with a bulk density of 220 - 360 g/L.
where R1group cyclic amide, such as 2H-3,4-dihydro-1,3-benzoxazin-2-she, 2H-3,4-dihydro-1,3-benzoxazin-2,4-dione, and 1,2,3,4-tetrahydroquinazoline-2,4-dione, and 1,2,3,4-tetrahydroquinazolin-2-it, 1,2,3,4-tetrahydropyrido(3,2-d)-pyrimidine-2,4 - dione, and 1,2,3,4-tetrahydropyrido(3,2-d)pyrimidine-2-it, 1,2,3,4-tetrahydropyrimidine-2,4-dione, pyrrolidin-2-it, 1,2,3,4 - tetrahydropyridine-2-it, 5H-6,7,8,9-tetrahydropyrido(3,2-b)azepin-6-she N-5,6,7,8-tetrahydropyrido(2,3-b)azepin - 8-she, 2H-3,4-dihydropyrido(2,3-e)-1, 3-oxazin-2-thione or 2-she pyrrolidine (3,4-b)-pyrazin-5-she 1H-2,3,4,5-tetrahydrothieno(2,3-b)indol-2-it, 8H-4,5,6,7-tetrahydrothieno(2,3-b)thiophene-7-she 4H-pyrazolo(5,4-f)benzazepin-9-it, isoindoline-1,3-dione, benzoxazolyl-2-it, unsubstituted or substituted lower alkyl, lower alkoxy, halogen, the nitro-group, carboxy, benzoyl or benzyl, n is zero or an integer from 1 to 6, Z is a group of formula (A) or (B):
N-(CH2)mR2(A) or -(CH2)p, dioxolane, furan, tetrahydrofuran, methylfuran or thiophene, m is an integer from 1 to 3; R3is lower alkyl; R4is phenyl or a radical of dioxolane, furan or thiophene, p = 1, provided that when R1radical 1,2,3,4-tetrahydrobenzo-2-or 1,2,3,4-tetrahydroquinazoline-2,4-dione, R2and R4are not phenyl or substituted by a halogen phenyl, or their pharmacologically acceptable salts with antiacetylcholinesterase activity
FIELD: organic chemistry, chemical technology, medicine, phthisiology.
SUBSTANCE: 4-thioureidoiminomethyl-pyridinium perchlorate is prepared from 4-pyridine aldehyde and thiosemicarbazide in the presence of 48-55% perchloric acid for a single stage. The parent reagents - 4-pyridine aldehyde : thiosemicarbazide are taken in the ratio = 1.3:1.0, reaction period is 3-4 h, and reaction temperature is maintained in the range 80-85°C. Invention provides increasing yield and purity of the end product, simplifying technology and reducing cost in its preparing.
EFFECT: improved preparing method.
7 cl, 8 ex
SUBSTANCE: invention refers to new compounds of general formula (I) where R1 stands for hydrogen or linear, branched, saturated or unsaturated hydrocarbon radical; D stands for nitrogen atom or C-R2; E stands for nitrogen atom or C-R3; F stands for nitrogen atom or C-R4; G stands for nitrogen atom or C-R5; R2, R3, R4 and R5 are identical or different and individually represent hydrogen, halogen, alkoxy, linear or branched, saturated or unsaturated hydrocarbon radical; W stands for oxygen atom; X stands for radical of formula radical -(CH2)k-C(O)-(CH2)m-, -(CH2)n- or -(CH2)r-O-(CH2)s-, where k, m, r and s are equal to integers 0 to 6, and n is equal to an integer 1 to 6. Said radicals are optionally substituted with one or more substitutes independently chosen from the group consisting of R7; Y stands for radical of formula radical -(CH2)i-NH-C(O)-(CH2)j-, -(CH2)n-, -(CH2)r-O-(CH2)s-, -(CH2)t-NH-(CH2)u-, where i, j, n, r, s, t and u are equal to integers 0 to 6. Said radicals are optionally substituted C1-3alkyl, or C1-3alkyl-C1-3alkylsulphonylamino; radicals R7, B, R8, A, R9 are as it is presented in the patent claim. The invention also describes the pharmaceutical composition possessing inhibitory activity of receptor tyrosine kinase to KDR receptor including described compounds.
EFFECT: compounds possess inhibitory activity of receptor tyrosine kinase to KDR receptor and can be effective in therapy of the diseases associated uncontrolled angiogenesis.
29 cl, 746 ex, 6 tbl
SUBSTANCE: in formula (1) compound, cysteinprotease is cathepsin K, cathepsin S, cathepsin L or cathepsin B. In formula (I) R is , AA1 is a bond, AA2 is a bond, R7 and R8 each independently represents hydrogen, C1-8 alkyl, CycA or C1-8 alkyl, substituted CycA, R9 is hydrogen, values of the rest of the radicals are given in the formula of invention. The invention also relates to a pharmaceutical composition, containing a formula (I) compound as an active ingredient, to a cysteinprotease inhibitor, method of inhibiting cysteinprotease, use of formula (I) compound in obtaining cysteinprotease inhibitor.
EFFECT: compound has inhibitory activity towards cysteinprotease.
10 cl, 16 tbl, 8 dwg, 224 ex
SUBSTANCE: invention relates to methods of producing formula I compounds and their salts, , where R1 is H or F; and Boc is tert-butoxycarbonyl. These compounds are useful as intermediate products during production of tryptase inhibitors.
EFFECT: invention also relates to intermediate products, which can be used when producing said compounds, as well as to methods of producing such intermediate products and their use in production of said compounds.
20 cl, 7 ex
SUBSTANCE: invention relates to a method of producing mono-imine compounds of formula where radicals assume values given in claim 1 of the invention, involving reaction of a dicarbonyl compound with aniline in an aliphatic non-aromatic solvent. The invention also describes an asymmetric iron complex of formula , where radicals assume values given in claim 3 of the invention, as well as a catalyst system for polymerisation of olefins.
EFFECT: invention describes mono-imine compounds having electron-attracting substitutes in the ortho-position and asymmetric bis(imino)-compounds and asymmetric iron compounds obtained from said compounds, and use of the complexes in olefin polymerisation.
7 cl, 11 ex, 1 tbl
SUBSTANCE: invention relates to a method of producing 4-thioureidoiminomethyl pyridinium perchlorate, having high tuberculostatic activity by reacting 4-pyridinoaldehyde, perchloric acid and thiosemicarbazide in an aqueous medium, wherein thiosemicarbazide is added to the obtained 4-pyridine aldehyde perchlorate (concentration of 28-46%) in molar ratio 4-pyridine aldehyde: thiosemicarbazide: perchloric acid of 1:1:1.05. The technical result is a novel simple, practically feasible and ecologically clean single-reactor method of producing pharmacopoeial 4-thioureidoiminomethyl pyridinium perchlorate (PERCHLOZONE®).
EFFECT: process does not require power consumption, additional heating or cooling.
3 cl, 7 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to 1-hydroxyimino-3-phenyl-propane derivatives of formula I, wherein R1 represents -(CH2)m-phenyl, m is equal to 0, and phenyl is substituted by 1-3 groups independently specified in C1-7-alkyl or hydroxy, or -(CH2)n-heteroaryl, wherein n is equal to 0 or 1, and heteroaryl is specified in pyridine, 1H-pyridin-2-one, 1-oxy-pyridine, 1H-pyrimidin-2-one, quinoline and pyrazine, and is ubsubstituted or substituted by 1-3 groups specified in the patent claim; R2 represents hydrogen or C1-7-alkyl, or when R4 represents hydrogen, R2 represents phenyl optionally substituted by C1-7-alkyl; R3 represents hydrogen; R5 represents hydrogen or hydroxy; or R3 and R5 are substituted by a double bond; R4 is specified in a group consisting of C1-7-alkyl, C3-7-cycloalkyl, C2-7-alkenyl, halogen-C1-7-alky, optionally substituted phenyl, optionally substituted phenyl-C1-7-alkyl, 5-9-merous heteroaryl containing 1-2 heteroatoms specified in N and S optionally substituted by C1-7-alkyl or oxo, and piperidinyl optionally substituted by C1-7-alkyl, or R4 and R5 together with a carbon atom to which they are attached, form a C3-7-cycloalkyl ring; R6 represents hydrogen halogen; or R4 and R6 together with a carbon atom to which they are attached, form a cyclic group G , wherein m represents 0 or 2; R7 - R9 are those as specified in the patent claim; R10 is specified in hydrogen, halogen and C1-7-alkyl; or their pharmaceutically acceptable salts. The invention also refers to specific compounds specified in cl. 19 of the patent claim, a method for producing the compounds I, a pharmaceutical composition, a method of treating diabetes and using the compounds for producing a medicinal agent.
EFFECT: 1-hydroxyimino-3-phenyl-propane derivatives possessing GPBAR1 agonist activity and effective in treating diabetes.
26 cl, 516 ex
SUBSTANCE: invention relates to medicine and pharmaceutics, namely to use of camphor imine derivatives of general formula I, where n=0, 1, 2; X=CH or N, R – hydroxy, alkoxy group, as inhibitors of reproduction of flu virus (strain A/California/07/09(H1N1)pdm09).
EFFECT: said imine compounds exhibit evident antiviral activity along with low toxicity.
1 cl, 1 tbl, 10 ex
SUBSTANCE: invention relates to O-substituted 3-pyridylketoksimes general formula I , where R1 It is 4-bromophenyl, 4-chlorophenyl, 4-fluorophenyl or cyclohexyl, R2 means hexyl, cyclohexyl or benzyl, having fungicidal activity.
EFFECT: expansion of the arsenal of agents having fungicidal activity.
3 tbl, 4 ex
SUBSTANCE: invention relates to substituted N-hydroxy-1-(3-pyridyl)prop-2-en-3-phenyl-1-imins of the general formula wherein R is benzyl, hexyl or cyclohexyl, Ar is 3-(trifluoromethyl)phenyl, 4-chlorophenyl, 4-bromophenyl or 4-fluorophenyl.
EFFECT: expansion of the arsenal of agents, which have fungicidal activity.
2 tbl, 4 ex
FIELD: organic chemistry, chemical technology, fungicides.
SUBSTANCE: invention describes derivative of benzoylpyridine of the formula (I) or its salt:
wherein X represents halogen atom, (C1-C6)-alkoxy-group optionally substituted with a substitute taken among halogen atom, phenyl, methoxy-, methylthio-, dimethylamino-group, vinyl or ethynyl; phenoxy-group, (C3-C6)-cycloalkoxy-group, hydroxyl group, (C1-C6)-alkyl group, (C2-C6)-alkenyl group, CF3, (C1-C6)-alkylthio-group, (C1-C6)-alkoxycarbonyl group, (C1-C6)-dialkylaminocarbonyl group, (C1-C6)-alkylcarbonyloxy-group, (C1-C6)-alkylcarbonyl group, amino-group, (C1-C4)-alkylamino-group or di-(C1-C4)-alkylamino-group; n represents 1, 2, 3 or 4; R1 represents (C1-C6)-alkyl group; R2 represents (C1-C6)-alkyl group, (C1-C6)-alkoxy-group optionally substituted with phenyl, phenoxy-group, (C3-C10)-cycloalkyloxy-group or hydroxyl group; m = 1, 2 or 3 under condition that if m = 2 then R2 can form ring -OCH2O- (with exception when pyridine ring is substituted with benzoyl group at 2-position; pyridine ring is substituted with (C1-C6)-alkoxy-group, hydroxyl group or benzyloxy-group; n = 1; m = 1 or 2). Also, invention describes fungicide comprising compound of the formula (I) or it salt as an active component, methods for preparing derivatives of benzoylpyridine, phenylpyridylmethanol that is an intermediate compounds used for synthesis of compound of the formula (I). Invention provides fungicide properties of compound of the formula (I) or its salt.
EFFECT: improved method for preparing, valuable properties of compounds.
17 cl, 36 tbl, 4 ex
FIELD: organic chemistry, medicine, pharmacy.
SUBSTANCE: invention relates to new derivatives of carboxylic acids of the formula: wherein Y is taken independently in each case among the group comprising C(O), N, CR1, C(R2)(R3), NR5, CH; q means a whole number from 3 to 10; A is taken among the group comprising NR6; E is taken among the group comprising NR7; J is taken among the group comprising O; T is taken among the group comprising (CH2)b wherein b = 0; M is taken among the group comprising C(R9)(R10), (CH2)u wherein u means a whole number from 0 to 3; L is taken among the group comprising NR11 and (CH2)n wherein n means 0; X is taken among the group comprising CO2H, tetrazolyl; W is taken among the group comprising C, CR15 and N; R1, R2, R3 and R15 are taken independently among th group comprising hydrogen atom, halogen atom, hydroxyl, alkyl, alkoxy-group, -CF3, amino-group, -NHC(O)N(C1-C3-alkyl)-C(O)NH-(C1-C3-alkyl), -NHC(O)NH-(C1-C6-alkyl), alkylamino-, alkoxyalkoxy-group, aryl, aryloxy-, arylamino-group, heterocyclyl, heterocyclylalkyl, heterocyclylamino-group wherein heteroatom is taken among N atom or O atom, -NHSO2-(C1-C3-alkyl), aryloxyalkyl; R4 is taken among the group comprising hydrogen atom, aryl, aralkyl, benzofuranyl, dihydrobenzofuranyl, dihydroindenyl, alkyl, benzodioxolyl, dihydrobenzodioxynyl, furyl, naphthyl, quinolinyl, isoquinolinyl, pyridinyl, indolyl, thienyl, biphenyl, 2-oxo-2,3-dihydro-1H-benzimidazolyl, pyrimidinyl and carbazolyl. Other values of radicals are given in the claimed invention. Also, invention relates to pharmaceutical composition used for inhibition binding α4β1-integrin in mammal based on these compounds. Invention provides preparing new compounds and pharmaceutical composition based on thereof in aims for treatment or prophylaxis of diseases associated with α4β1-integrin.
EFFECT: improved method for inhibition, valuable medicinal properties of compounds.
33 cl, 7 tbl, 42 ex
FIELD: organic chemistry, medicine, pharmacy.
SUBSTANCE: invention relates to new nitrogen-containing aromatic derivatives of the general formula:
wherein Ag represents (1) group of the formula:
; (2) group represented by the formula:
or ; (3) group represented by the formula:
; Xg represents -O-, -S-, C1-6-alkylene group or -N(Rg3)- (wherein Rg3 represents hydrogen atom); Yg represents optionally substituted C6-14-aryl group, optionally substituted 5-14-membered heterocyclic group including at least one heteroatom, such as nitrogen atom or sulfur atom, optionally substituted C1-8-alkyl group; Tg1 means (1) group represented by the following general formula:
; (2) group represented by the following general formula: . Other radical values are given in cl. 1 of the invention claim. Also, invention relates to a medicinal agent, pharmaceutical composition, angiogenesis inhibitor, method for treatment based on these compounds and to using these compounds. Invention provides preparing new compounds and medicinal agents based on thereof in aims for prophylaxis or treatment of diseases wherein inhibition of angiogenesis is effective.
EFFECT: improved treatment method, valuable medicinal properties of compounds and agents.
40 cl, 51 tbl, 741 ex
FIELD: organic chemistry, herbicides, agriculture.
SUBSTANCE: invention elates to novel derivatives of uracil of the formula [I] possessing herbicide activity, a herbicide composition based on thereof and to a method for control of weeds. In derivatives of uracil of the formula [I] the group Q-R3 represents a substituted group taken among:
wherein a heterocyclic ring can be substituted with at least a substitute of a single species taken among the group involving halogen atom, (C1-C6)-alkyl-(C1-C6)-alkoxy; Y represents oxygen, sulfur atom, imino-group or (C1-C3)-alkylimino-group; R1 represents (C1-C3)-halogenalkyl; R2 represents (C1-C3)-alkyl; R3 represents OR7, SR8 or N(R9)R10; X1 represents halogen atom, cyano-group, thiocarbamoyl or nitro-group; X2 represents hydrogen or halogen atom wherein each among R7, R8 and R10 represents independently carboxy-(C1-C6)-alkyl and other substitutes given in the invention claim; R9 represents hydrogen atom or (C1-C6)-alkyl. Also, invention relates to intermediate compounds used in preparing uracil derivatives.
EFFECT: improved preparing method, valuable properties of compounds.
40 cl, 16 sch, 12 tbl, 65 ex
FIELD: organic chemistry, medicine, pharmacy.
SUBSTANCE: invention relates to new derivatives of 4-phenylpyridine of the general formula: (I) wherein R means halogen or halogen atom; R1 means -(C≡C)mR1' or -(CR'=CR'')mR1'; X means -C(O)N(R8)-, -N(R8)C(O)- or -N(R8)-(CH2)p- wherein m = 0-4 and p = 1-2; values of radicals R1', R2, R3', R3, R4, R4', R8, R' and R'' are given above, and to their pharmaceutically acceptable acid-additive salts and a medicinal agent based on thereof. New compounds are neurokinine-1 antagonists and can be used as medicinal agents in treatment of diseases mediated by neurokinine-1 receptors.
EFFECT: valuable medicinal properties of derivatives.
13 cl, 119 ex