The way to obtain a 6-substituted orallow
(57) Abstract:The invention relates to an improved process for the preparation of 6-substituted orallow General formula I, where R = CH3WITH6H5CH2, 2,6-F2WITH6H3CH2that can be used in the pharmaceutical industry to obtain drugs. The method consists in the interaction of 6-substituted 2-thiouracil, selected from the group comprising 6-methyl-2-thiouracil, 6-benzyl-2-thiouracil, 6-(2,6-diferensial)-2-thiouracil, 2-methyloxirane in the presence of an aqueous solution of sodium hydroxide at a molar ratio of 6-substituted 2-thiouracil : 2-methyloxiran : sodium hydroxide is 1:1,0-1,2: 1, followed by acidification and isolation of the target product. The method allows to carry out the process under mild conditions, using cheap raw materials, excluding the presence of acidic waste and obtaining the target product with practically quantitative yield.The present invention relates to the field of synthesis of heterocyclic compounds, specifically to a method for producing 6-substituted uracil derivative of the formula
< / BR>where R = CH3WITH6H5CH2, 2,6-F2C
< / BR>where R = CH3WITH6H5CH2, 2,6-F2C6H3CH2using 6-substituted 2-thiouracil in the presence of an aqueous solution of sodium hydroxide, characterized in that as a 6-substituted 2-thiouracil use 6-methyl-2-thiouracil, 6-benzyl-2-thiouracil or 6-(2,6-diferensial)-2-thiouracil, which is subjected to interaction with 2-methyloxirane at a molar ratio of 6-substituted 2-thiouracil : 2-methyloxiran : sodium hydroxide is 1:1.0-1.2:1, followed by separation of the target product.The essence of the proposed method is currency ekzoticheskogo the sulfur atom of 2-thiouracil on oxygen 2-methyloxirane with the formation of the target uracil with practically quantitative yield
< / BR>Using 2-methyloxirane for desulphurization derivatives of 2-thiouracil is unconventional. While the reaction with oxirane similarly behave Rodney, thiocarbamide and thiosulfate, Wei obtaining substituted S-(2-hydroxyethylene) derivatives. The use of sodium hydroxide in the proposed process, it is necessary to convert the original 6-substituted 2-thiouracil in the water-soluble sodium salt. In addition, the anion of 2-thiouracil is a particle, which in the first stage carries out a nucleophilic attack on the three oxiranyl cycle. The use of a small excess of 2-methyloxirane due to the need to achieve complete conversion of the initial derivative of 2-thiouracil in the derivative of uracil due to the significant volatility 2 methyloxirane.The advantage of this method is the possibility of obtaining almost any derivatives of uracil, many of which are used as intermediates for the synthesis of medicinal substances in a single phase with a quantitative yield, as well as preparative ease of synthesis and ease of separating pure reaction products.The proposed method is as follows.To aqueous sodium hydroxide solution was added 6-substituted 2-thiouracil and stirred at a temperature of 40-50oWith up to dissolution. To the resulting solution was cooled to room temperature, with stirring, was added 2-methyloxiran at a molar ratio of 6-substituted 2-teature. After this time the reaction mixture was adjusted with concentrated hydrochloric acid to pH 5, stirred and filtered. The precipitate is washed with water and air-dried to constant weight.The invention is illustrated by the following examples.Example 1.< / BR>Synthesis of 6-methyluracil.To 16 ml of 0.25 M aqueous sodium hydroxide solution added, the original 6-methyl-2-thiouracil (0,57 g, 4 mmole) and stirred at a temperature of 40-50oWith up to almost complete dissolution. To the resulting solution was cooled to room temperature, with stirring, was added 2-methyloxiran (2.55 g, 4.4 mmole), the ratio of the initial reagents: 6-methyl-2-thiouracil : 2-methyloxiran : sodium hydroxide = 1:1.1:1. The reaction mass is stirred for 24 hours at room temperature. After this time the reaction mixture was adjusted with concentrated hydrochloric acid to pH 5, stirred for another 10 minutes and filtered. The precipitate was washed with water (10 ml) and air-dried to constant weight. Output 6-methyluracil - quantitative.So pl. = 300oWith decomposition, which corresponds to literature data (The Merck Index, 12-th Ed., 1996, p. 6212).Example 2.< / BR>Synthesis of 6-benzylurea.Output 6-benzylurea - quantitative.So pl. = 261-262oS, which corresponds to literature data (Johnson T. C., Ambelang J. C., J. Am. Chem. Soc., 1938, v. 60, R. 2941).Example 3.< / BR>Synthesis of 6-(2,6-diferensial)uracil.Is carried out analogously to synthesis 1, except for use as 6-substituted 2-thiouracil 6-(2,6-diferensial)-2-thiouracil (1,02 g, 4 mmole). The ratio of initial reagents 6-(2,6-diferensial)-2-thiouracil: 2-methyloxiran: sodium hydroxide = 1:1.1:1.Yield 6-(2,6-diferensial)uracil - quantitative.Decomposes above 300oC.Mass spectrum m/e: 256 (M+ H + F, 7%), 238 (M+, 32%), 219 (M+ -F, 0,1%), 195 (M+-HNCO, 0,8%), 175 (M+ - F - HNCO, 14%), 152 (M+ -2 HNCO, 8%) 127 (2,6-F2WITH6H3CH2, 27%), 68 (M+ - 2,6 - F2C6H3CH2-HNCO, 100%).IR spectrum (KBr): 1660 cm-1 (C=0).Example 4.Synthesis of 6-(2,6-diferensial)uracil.Is similar to that for synthesis of 3, except for the ratio of initial reagents 6-(2,6-diferensial)-2-thiouracil : 2-methyloxiran : sodium hydroxide = 1:1.2:1.Yield 6-(2,6-diferensial)-2-thiouracil is illogical synthesis of 3, except for the ratio of initial reagents 6-(2,6-diferensial)-2-thiouracil : 2-methyloxiran : NaOH = 1:1:1.Yield 6-(2,6-diferensial)uracil - 92%.It follows from the presented examples, we proposed a method of obtaining a 6-substituted derivatives of orallow is a technology that allows to obtain a wide range of these compounds with quantitative yield and high purity. The way to obtain a 6-substituted orallow General formula
< / BR>where R = CH3WITH6H5CH2, 2,6-F2WITH6H3CH2< / BR>using the 6-substituted 2-thiouracil in the presence of an aqueous solution of sodium hydroxide, characterized in that as a 6-substituted 2-thiouracil use 6-methyl-2-thiouracil, 6-benzyl-2-thiouracil or 6-(2,6-diferensial)-2-thiouracil, which is subjected to interaction with 2-methyloxirane at a molar ratio of 6-substituted 2-thiouracil: 2-methyloxiran: sodium hydroxide is 1: 1,0-1,2: 1, followed by acidification and isolation of the target product.
< / BR>where R denotes cyclopropyl, cyclobutyl, cyclohexyl, phenyl, unsubstituted or mono -, di - or tizamidine group selected from hydroxy, C1-C4of alkyl, C1-C4alkoxy, halogen, trifloromethyl, ceanography and amino groups; 1-or 2-naphthyl, 9-anthracene; 2-anthrachinone, Persil, unsubstituted or substituted group selected from1-C4of alkyl, C1-C4alkoxy, ceanography and halogen; 2-, 3 - or 4-chinoline, oxiranyl, 1-benzotriazolyl, 2-benzoxazolyl, furanyl, substituted C1-C4alkoxycarbonyl; C1-C4alkylsulphonyl or benzoyl; R1denotes halogen or1-C4alkyl, R2and R3independently represent hydrogen or C1-C4alkyl; X denotes an oxygen atom and Y represents an oxygen atom, a sulfur atom or a carbonyl, or their pharmaceutically acceptable salts, method of production thereof and pharmaceutical composition having antiviral activity, containing antiviruse-effective amount of compounds of General formula I
< / BR>moreover, if the group-CH2-NR2R3located in the para-position relative to the group of SO2the rest of the sulfonylureas, R3does not mean the unsubstituted alkylsulphonyl with 1-6 carbon atoms in the alkyl part, R2and R3together mean a group of the formula (CH2)m- Or-B1-(CH2)m1-B-, where b and b
FIELD: organic chemistry, herbicides, agriculture.
SUBSTANCE: invention relates to new derivatives of uracil of the formula [I] eliciting the herbicide effect, herbicide composition based on thereof and a method for suppression of weed growth. In the formula [I] W means oxygen (O), sulfur (S) atom or imino-group; Y means oxygen atom (O) or sulfur atom (S); R1 means (C1-C3)-alkyl or (C1-C3)-halogenalkyl; R2 means (C1-C3)-alkyl; R4 means hydrogen atom (H) or methyl; R5 means (C1-C6)-alkyl, (C1-C6)-halogenalkyl, (C3-C6)-alkenyl, (C3-C6)-halogenalkenyl, (C3-C6)-alkynyl or (C3-C6)-halogenalkynyl; X1 means halogen atom, cyano- or nitro-group; X2 means hydrogen atom (H) or halogen atom; each among X3 and X4 means independently hydrogen atom (H), halogen atom, (C1-C6)-alkyl, (C1-C6)-halogenalkyl, (C3-C6)-alkenyl, (C3-C6)-halogenalkenyl, (C3-C6)-alkynyl, (C3-C6)-halogenalkynyl, (C1-C6)-alkoxy-(C1-C6)-alkyl, (C1-C6)-alkoxy-, (C1-C6)-halogenalkoxy-, (C1-C6)-alkoxycarbonyl-(C1-C6)-alkoxy- or cyano-group. Also, invention relates to new intermediate substances used for preparing compounds of the formula [I] corresponding to formulae [VII] , [XXXIV] and [XXXIII] wherein in compound of the formula [VII] W means oxygen (O), sulfur (S) atom or imino-group; Y means oxygen (O) or sulfur atom (S); in compounds of formulae [XXXIV] and [XXXIII] W means oxygen atom (O); R17 means oxygen atom (O); R4 means hydrogen atom (H) or methyl. Also, invention relates to methyl- or ethyl-[2-(5-amino-2-chloro-4-fluorophenoxy)phenoxy]acetate not early described in the literature.
EFFECT: valuable herbicide properties of compounds.
23 cl, 17 sch, 9 tbl, 11 ex
FIELD: organic chemistry, microbiology.
SUBSTANCE: invention relates to new synthetic biologically active derivatives of pyrimidine, namely to 2,4-dioxo-5-(2-hydroxy-3,5-dichlorobenzylidene)imino-1,3-pyrimidine potassium, sodium or ammonium salt of the general formula: wherein X is taken among the group: Na+, K+, NH+ 4. The claimed substance shows expressed antibacterial activity directed mainly against different fungi, bacteria, protozoan and viruses.
EFFECT: valuable biological properties of compounds.
13 tbl, 13 ex
FIELD: organic chemistry, medicine, pharmacy.
SUBSTANCE: invention relates to novel 4-pyrimidinyl-N-acyl-L-phenylalanines of the formula (I)
or their pharmaceutically acceptable salts possessing ability to inhibit binding VCAM-1 with integrin VLA-4 (α4β1) or with cells expressing VLA-4 and useful in preparing medicinal agents used in treatment of, for example, rheumatic arthritis, cerebrospinal sclerosis, intestine inflammation and asthma. In compound of the formula (I) R1 means group of the formula (Y-1): wherein R22 and R23 mean independently hydrogen atom, lower alkyl, lower alkoxy-group, halogen atom or perfluoro-lower alkyl and at least one among R22 and R23 doesn't mean hydrogen atom; R24 means hydrogen atom, lower alkyl, lower alkoxy-group; or R1 means group of the formula (Y-3) that means 3-7-membered cycle of the formula (Y-3): wherein R25 means group of the formula: R26-(CH2)e- wherein R26 means lower alkoxy-group; Q means -(CH2)fN(R27)-, -(CH2)f- wherein R27 means hydrogen atom (H) or lower alkoxycarbonyl, and carbon atoms in cycle are unsubstituted; e means a whole number from 1 to 4; f means a whole number from 1 to 3; R2 means hydrogen atom or lower alkyl; R3 means hydrogen atom or lower alkyl; R4 means hydrogen atom, lower alkyl, lower alkyl substituted with halide; R5 means hydrogen atom or lower alkyl; R6 means hydrogen atom, lower alkyl, lower alkylcarbonyloxy-lower alkyl, or R6 means group of the formula (P-3): wherein R32 means hydrogen atom; R33 means lower alkyl; R34 means lower alkyl wherein R32 means hydrogen atom; R33 means lower alkyl; R34 means lower alkyl; h means a whole number from 0 to 2; g means a whole number from 0 to 2; h + g = 1-3; or R6 means group of the formula (P-4):
wherein R32, g and h have values given above; Q' means oxygen atom (O). Also, invention relates to pharmaceutical compositions.
EFFECT: valuable medicinal properties of compounds and compositions.
37 cl, 8 sch, 3 tbl, 42 ex
FIELD: organic chemistry, biochemistry.
SUBSTANCE: invention proposes compound of the formula (1) in free form or as a salt wherein R1, R2, R3, R4 and R5 have values given in the invention claim. The claimed compounds are selective inhibitors of enzyme PDE-5 and show the high selectivity in inhibition of activity of 3',5'-cycloguanosine monophosphate phosphodiesterase being activity of PDE-5 first of all.
EFFECT: valuable biochemical properties of derivatives.
6 cl, 3 tbl, 87 ex
FIELD: organic chemistry, medicine.
SUBSTANCE: invention relates to compounds of the formula (I): and their salts, to methods for their preparing, compositions containing thereof and their using in medicine, in particular, for prophylaxis or treatment of clinical state wherein a selective agonist of β2-adrenoceptors is prescribed.
EFFECT: valuable medicinal properties of compound and compositions.
32 cl, 4 dwg, 82 ex
SUBSTANCE: claimed invention relates to benzenesulphonamide derivatives of formula I and to their salts applied in agriculture. In formula I
X1 represents hydrogen or halogen; X2 chlorine; X3 represents hydrogen; Y represents group -C(A)B; A represents oxygen; B represents oxygen; R1 represents C1-C6-alkyl, which can be optionally substituted with C1-C6-alkoxyl, C1-C6-alkylcarbonyl, C3-C7-cycloalkyl, phenyl-C1-C4-alkyl; Q represents residue Q21; A8, A9 represent oxygen; R29 represents C1-C6-alkyl; R30, R31 represent hydrogen, C1-C6-halogenalkyl.
EFFECT: elaboration of method for obtaining benzenesulphonamide derivatives of formula I, herbicidal preparation based on them, method of obtaining herbicidally active preparations, method used to fight undesirable plant growth, application as herbicides and to benzenesulphonylisocyanates of formula II.
8 cl, 4 tbl, 6 ex
SUBSTANCE: invention concerns novel compounds of formula (1a) or (1b) or their pharmaceutically acceptable salts with inhibition effect on matrix metalloproteinases (MMP). In formula
or T is absent; G1 and G2 is independently CH or N; A is C1-6alkyl; B is a link; D is a link; E is phenyl substituted by condensed heterocyclic ring in the form of nitrogen-containing ring which can be substituted by carbonyl groups; or substituted 6-membered heteroaryl or bicyclic heteroaryl where second ring in bicyclic system is benzene ring, and heteroaryl is 5-6-membered ring containing 1, 2 or 3 nitrogen heteroatoms, and heteroaryl is substituted by 1, 2 and 3 groups selected out of oxo and C1-6alkyl-; R16 is C1-6alkyl; R18 is halogeno, cyano, nitro, OR16 , OCF3, SR16 or COR16; m is 0 or integer 1 or 2; n is 0.
EFFECT: obtaining compounds and pharmaceutical composition based on them.
13 cl, 18 ex
SUBSTANCE: invention relates to an improved method of producing 5-amino-6-methyluracil of formula: , by reacting 5-bromo-6-methyluracil with aqueous ammonia in preferable molar ratio of reagents of 1:11 and temperature 110-140°C for 16-20 hours followed by extraction of the product.
EFFECT: simple process and high cost effectiveness while maintaining high output of the product.
SUBSTANCE: agent is derivatives of bis(5-methylaminomethyluracil)polymethylene of formula (I) or pharmaceutically acceptable salts thereof
The agent is specifically a compound selected from: 5-[4-(2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinylmethylamino)propylaminomethyl]-1,2,3,4-tetrahydro-2,4-pyrimidine dione (n=1); 5-[4-(2,4-dioxo-1,2,3,4-tetrahydro-5- pyrimidinylmethylamino)butylaminomethyl]-1,2,3,4-tetrahydro-2,4-pyrimidine dione (n=2);5-[4-(2,4-dioxo-1,2,3,4-tetrahydro-5- pyrimidinylmethylamino)pentylaminomethyl]-1,2,3,4-tetrahydro-2,4-pyrimidine dione (n=3) and 5-[4-(2,4-dioxo-1,2,3,4-tetrahydro-5- pyrimidinylmethylamino)hexylaminomethyl]-1,2,3,4-tetrahydro-2,4- pyrimidine dione (n=4). The disclosed compound was found to have in vitro capacity to increase activity of di- and polyamine oxidase, reduce ornithine decarboxylase activity, particularly in tumour cells, specifically tumour cells of human ovarian carcinoma. The disclosed compounds have in vitro low cytotoxicity. The invention also relates to a method of slowing down tumour cell proliferation using compounds of formula (1).
EFFECT: improved properties of inhibitor of formation of polyamines, low rate of tumour cells proliferation.
6 cl, 4 dwg, 11 tbl, 4 dwg
SUBSTANCE: nucleic base (e.g. uracil, cytosine, adenine, guanine, hypoxanthine, xanthine or similar) reacts with perfluoroalkyl halide in the presence of sulphoxide, peroxide and an iron compound to obtain a perfluoroalkyl-substituted nucleic base.
EFFECT: high cost effectiveness as an intermediate compound for producing medicinal agents.
15 cl, 6 tbl