Chiral diacylhydrazine ligands for modulation of exogenous genes expression by ecdysone-receptor complex

FIELD: biotechnology.

SUBSTANCE: invention relates to a method for preparation of an enantiomerically enriched compound with Formula III , wherein A is (C1-C6)alkyl-O-, phenyl- C1-C6)alkyl-O-; aryl selected from phenyl, naphthyl, benzo 1,3]dioxole, 2,3-benzo[1,4]dioxin which is optionally substituted by 1 to 3 substituents, where the substituents are selected from (C1-C6) alkyl, (C3-C7) cycloalkyl, (C1-C6)alkyl-O-, hydroxy, amino and halo; or heteroaryl having four or five carbon atoms and one heteroatom selected from oxygen, nitrogen and sulfur, which is optionally substituted by 1 to 3 substituents, where the substituents are selected from (C1-C6)alkyl, (C3-C7)cycloalkyl, (C1-C6)alkyl-O-, hydroxy, amino and halo; B is phenyl optionally substituted by 1 to 3 substituents, where the substituents are selected from (C1-C6)alkyl, (C3-C7)cycloalkyl, (C1-C6)alkyl-O-, hydroxy, amino and halo; and R1 and R2 independently represent (C1-C6)alkyl, phenyl-(C1-C6)alkyl-, hydroxy-(C1-C6)alkyl, (C3-C7)cycloalkyl, (C2-C6)alkenyl or (C2-C6)alkynyl; provided that R1 differs from R2; where the absolute configuration of the asymmetric carbon atom carrying R1 and R2, is an R-configuration; including (a) reaction of Formula XI acylhydrazine with Formula XII ketone to form a compound of Formula XIII , where R1 differs from R2, (b) reduction of the Formula XIII compound in the presence of a chiral catalyst to form a Formula R-XIV compound and (c) reaction of the Formula R-XIV compound with the Formula B-CO-LG compound, wherein LG is a leaving group, forming a compound with Formula III.

EFFECT: chiral diacylhydrazine ligands for genome modulation.

6 cl, 25 dwg, 11 tbl

 



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention relates to biochemistry, particularly to an isolated nucleic acid molecule which codes a polypeptide, having delta-9-elongase activity, as well as a purified polypeptide having delta-9-elongase activity, which codes said isolated nucleic acid molecule. The invention also discloses an expression vector containing said isolated nucleic acid molecule, as well as a host cell, a transgenic plant and a transgenic seed containing same.

EFFECT: invention provides efficient production of polyunsaturated fatty acid-enriched oils.

18 cl, 9 dwg, 9 tbl, 6 ex

FIELD: agriculture.

SUBSTANCE: invention relates to the field of agricultural biotechnology. Method of producing dihaploid plants of barley from cultured microspores in vitro, comprising: growing donor plants at reduced air temperature of 15-20°C, light regime: 16 h day/8 h night, relative humidity of 60-70%, lighting intensity of 10000-15000 lux, with carrying out phytosanitary treatment, at that growing donor plants is carried out to the stage from opening of the sheath, when the inflorescence is in the flag leaf, - stress treatment of ears at 4°C, in tubes with a poor environment containing KCl - 1.5 g/l, MgSO4×7H2O - 0.25 g/l, CaCl2×2H2O - 0.1 g/l, mannitol - 60 g/l, potassium phosphate buffer - 1 ml/l, pH 7.0, for 7 days for shifting from gametophytic development path of microspore to sporophytic path - microspore isolation from spikelets in sterile conditions, - culturing the isolated microspores in a modified environment for embryogenesis induction, consisting of 6% maltose, 10 sets per 1.5 ml of the culture, and plant growth regulators in amount of 1 mg/l 2,4-D, 0.2 mg/l zeatin, and adding the aforementioned components is carried out before the addition of microspores, - regenerating plants from embryoids by culturing on solid nutrient Murashige and Skoog medium without the adding of plant growth regulators, - processing the barley haploid plants with antimitotic agent N-diacetyl-N-(β,γ-epoxypropyl) aminocolchicine for doubling chromosomes and obtaining dihaploid plants.

EFFECT: invention enables to obtain dihaploid homozygous lines of barley for breeding new varieties and hybrids with improved properties.

1 dwg, 2 tbl, 6 ex

FIELD: chemistry.

SUBSTANCE: invention relates to biochemistry, providing a method for introducing a sequence specific nuclease (SSN) into a plant cell. The method comprising: providing the plant cell having a cell wall; coating a gold nanoparticle with a SSN; placing the cell having a cell wall and the coated nanoparticle in contact with each other; incubating the cell having a cell wall with a coated nanoparticle to allow uptake of the nanoparticle and the SSN into the plant cell comprising a cell wall.

EFFECT: invention provides a method for efficient introduction of SSN into a plant cell comprising a cell wall.

14 cl, 7 dwg, 5 ex

FIELD: chemistry.

SUBSTANCE: invention relates to biochemistry, particularly to use of a protein-coding gene, which consists of an amino acid sequence represented in SEQ ID NO.2, to obtain transgenic rice with long, large and multiple grains and increased yield, more grains per panicle and rolled leaves. Disclosed is use of a transgenic cell line of rice and a recombinant vector to obtain transgenic rice with long, large or multiple grains and increased yield, more grains per panicle and rolled leaves.

EFFECT: invention enables to efficiently obtain transgenic rice with long, large or multiple grains and increased yield, more grains per panicle and rolled leaves.

5 cl, 16 dwg, 4 tbl, 2 ex

FIELD: chemistry.

SUBSTANCE: invention refers to biochemistry, particularly to a method for weed control near sunflower plants. The method involves applying an effective amount of any of the herbicides specified in a group consisting of imidazolinone herbicide, sulphonylurea herbicide, triazolopyrimidine herbicide, pyrimidinyloxybenzoate herbicide and their mixture, on weeds and sunflower plants. The above sunflower plant contains in its genome at least one copy of at least acetohydroxyacid synthase (AHAS) gene coding a herbicide-resistance protein having an amino acid sequence presented by SEQ ID NO:2.

EFFECT: invention enables controlling weeds near sunflower plants effectively.

9 cl, 13 dwg, 14 tbl

Farnesene-synthase // 2546877

FIELD: chemistry.

SUBSTANCE: invention relates to the field of biotechnology. Claimed are: a separated from the tomato polynucleotide, corresponding to SEQ ID NO:1, presented in the description, or a polynucleotide, which has, at least, a 70% identity with the nucleotide sequence SEQ ID NO:1, or their fragment, which code a polypeptide with the activity of farnesene-synthase, corresponding to SEQ ID NO:2, presented in the description, or having, at least, a 70% identity with an amino acid sequence, corresponding to SEQ ID NO:2, or their fragment. Genetic constructions, containing the said polynucleotide, where genetic constructions represent a transformation vector and an expression vector are described. Described is the transformation vector, which contains the polynucleotide which is hybridised with a polynucleotide, coding the said polypeptide. A host cell for expression farnesene-synthase, which contains a genetic construction, selected from the said ones, is described. Claimed is a method of obtaining alpha-farnesene and/or beta-farnesene, including stages of the said host cell cultivation with obtaining the increased activity of alpha-farnesene synthase and/or activity of beta-farnesene-synthase and optionally obtaining a cell with farnesyldiphosphate; and the separation of the obtained alpha-farnesene and/or beta-farnesene. Described is a method of modulating the production of alpha-farnesene and beta-farnesene by a plant, which includes an increase or reduction of expression of the said farnesene-synthase, where the said increase or reduction is achieved by means of genetic modification to change the expression of polynucleotide, coding the said polypeptide. Claimed is the application of the polynucleotide in accordance with the claimed invention for coding a molecular (DNA) marker, bound with the said nucleotide sequence.

EFFECT: invention makes it possible to obtain alpha-farnesene and beta-farnesene in the host cell.

16 cl, 8 dwg, 1 tbl, 1 ex

FIELD: medicine.

SUBSTANCE: invention refers to biochemistry, particularly to a gene expression construct containing: (a) an expression enhancer sequence produced of RNA-2 genome segment of two-component RNA-virus of the family Comoviridae, b) a polylinker for facilitating a gene insertion into a gene expression system. What is disclosed is a gene expression vector containing the above construct and heterologous gene. What is also described is the gene expression vector containing: (a) the expression enhancer sequence produced of RNA-2 genome segment of two-component RNA-virus of the family Comoviridae, (b) the heterologous gene, which codes a protein of interest, as well as a method for expressing the protein of interest with using it. A method for increasing translation enhancement activity of the heterologous protein of interest from the heterologous gene coding the above protein, a method for translation enhancement of the heterologous protein of interest from the heterologous gene or a heterologous open reading frame coding the above protein are disclosed. There are also described a host organism transformed by the above vector, as well as a method for producing the protein of interest, involving collection of the host organism tissue.

EFFECT: invention enables enhancing translation of the heterologous protein of interest from the heterologous gene.

26 cl, 15 dwg, 4 tbl, 6 ex

FIELD: chemistry.

SUBSTANCE: invention relates to the field of biochemistry, in particular to a method of increasing biomass or improvement of cell proliferation, leaf development and/or reproductive development of a plant, which includes increasing expression in the plant of nucleic acid, coding the ubiquitin-specific protease, as well as to the plant, a part of the plant and a seed of the plant, biomass of which is increased, or cell proliferation, leaf development and/or reproductive development of which are increased by the said method. A vector for application in the method of obtaining plants with increased biomass or improved cell proliferation, leaf development and/or reproductive development, as well as the plant and the part of the plant, transformed with the said vector, are described. Application of nucleic acid, coding the ubiquitin-specific protease is disclosed. Also disclosed is a method of obtaining a transgenic plant with increased biomass or improved cell proliferation, leaf development and/or reproductive development, as well as the transgenic plant with increased biomass or improved cell proliferation, leaf development and/or reproductive development in comparison with the control plants, obtained as a result of increased expression of nucleic acid, coding the ubiquitin-specific protease.

EFFECT: invention makes it possible to efficiently obtain the plant with increased biomass or improved cell proliferation, leaf development and/or reproductive development.

17 cl, 11 dwg, 3 tbl, 28 ex

Transgenic plants // 2515927

FIELD: chemistry.

SUBSTANCE: invention relates to field of biochemistry, in particular to genetic construction for expression of threonine-insensitive aspartate kinase in plant, where construction contains promoter, specific for phase of aging, functionally connected with coding sequence, which codes polypeptide, possessing activity threonine-insensitive aspartate kinase, and in which specific to aging promoter is selected from group, consisting of SAG12, SAG13, SAG101, SAG21 and SAG18, or their functional variants or fragments. Described are vector, plant cell, transgenic plant, material for plant reproduction, collected leaves, smoking tobacco, which contain claimed genetic construction. Also described is method of obtaining transgenic plant, which possesses ability to accumulate threonine in fading leaves in larger amount than in leaves of corresponding plant of wild type, and method of increasing the level of threonine in leaves of aging plant to the level of threonine, higher than the content of threonine in leaves of plant of wild type without impairing plant adaptation with application of said genetic construction.

EFFECT: invention makes it possible to obtain transgenic plant, which possesses ability to accumulate threonine in fading leaves in larger amount than in leaves of plant of wild type.

22 cl, 16 dwg, 2 tbl, 4 ex

FIELD: chemistry.

SUBSTANCE: invention relates to field of biochemistry, in particular to methods of targeted change of duplex acceptor DNA-sequence and improvement of efficiency of targeted mutagenesis in plant protoplasts. Claimed methods include introduction into protoplasts of plant cells of single-stranded mutagenic oligonucleotide, which in its composition has, at least, one wrong nucleotide with respect to duplex acceptor DNA-sequence, which is to be changed with application of PEG-mediated transformation.

EFFECT: invention makes it possible to increase frequency of targeted mutagenesis.

10 cl, 3 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of general formula III and their pharmaceutically acceptable salts, A represents (C1-C6)alkyl-O-, phenyl-(C1-C6)alkyl-O-; aryl, selected from phenyl, naphthyl, and which is possibly substituted by 1-3 substituents, given in the invention formula; or heteroaryl, which has four or five carbon atoms and one heteroatom, selected from oxygen, nitrogen and sulphur, which is possibly substituted by 1-3 substituents, given in the invention formula; B represents phenyl, possibly substituted by 1-3 substituents, where substituents are selected from (C1-C6)alkyl, (C3-C7)cycloalkyl, (C1-C6)alkyl-O-, hydroxy, amino and halogeno; and R1 and R2 independently represent (C1-C6)alkyl, phenyl-(C1-C6)alkyl-, hydroxy-(C1-C6)alkyl, (C3-C7)cycloalkyl, (C2-C6)alkenyl or (C2-C6)alkynyl; on condition that R1 is different from R2; where absolute configuration of asymmetric R1 and R2 -carrying carbon atom is mainly R-configuration. Invention also relates to pharmaceutical composition, possessing ability to modulate gene expression, methods of modulation of gene expression in host cell, method of regulating expression of endogenous or heterologous gene in transgenic subject, method of regulating transgenic expression in transgenic subject, method of polypeptide production and to method of obtaining formula IV compound. Method includes stages: a) interaction of formula V compound with formula IV compound with obtaining formula VII compound; b) reduction of formula VII compound with obtaining formula VIII compound, b) interaction of formula VIII compound with formula B-CO-LG compound, where B has values, given above, and LG is leaving group representing -F, -Cl or -Br, with formation of formula IX compound, d) removal of group R7CO2- from formula IX compound with obtaining formula X compound, e) interaction of formula X compound with formula A-CO-LG compound, where A has values, given above, and LG is leaving group, representing -F, -Cl or -Br, with obtaining formula IV compound ( compounds of formulas V, VI, VII, VIII, IX, X are given in the invention formula).

EFFECT: obtaining formula III compounds, possessing ability to modulate gene expression.

19 cl, 4 ex, 2 tbl, 78 ex

FIELD: chemistry.

SUBSTANCE: invention relates to organic chemistry and specifically to novel biologically active substances of the class of 4-aryl-2,4-dioxobutanoic acids. Disclosed is 4-(4-bromophenyl)-4-oxo-2-{[3-ethoxycarbonyl)-4,5-dimethylthien-2-yl]amino}-2-butenoic acid, having anti-inflammatory and analgesic activity, of formula (1): .

EFFECT: obtaining a compound with high output, having marked anti-inflammatory and analgesic activity as well as low toxicity.

1 cl, 1 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: declared method refers to preparing 4-methyl-3-[2-(N-propylamino)propionylamino]thiophene-2-carboxylic acid methyl ether hydrochloride (articaine) which is implemented by a reaction of 3-(2-chloropropionyl)amino-4-methyl-2-methoxycarbonylthiophene and n-propylamine, transformation of the reaction product into an aqueous solution in the form of hydrochloride which is used to recover 4-methyl-3-[2-(N-propylamino)propionylamino]thiophene-2-carboxylic acid methyl ether hydrochloride by introducing sodium chloride in the amount to provide the concentration of the latter in the reaction mass within the range of 10.0 to 15.0%. The technical effect consists in the fact that there is developed the method for preparing high-yield and high-purity 4-methyl-3-[2-(N-propylamino)propionylamino]thiophene-2-carboxylic acid methyl ether hydrochloride.

EFFECT: prepared product is a local anaesthetic found a wide application in dentistry and surgical practice.

1 cl, 1 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing 3-(2-chloropropionyl)amino-4-methyl-2-methoxycarbonylthiophene by acylation of 3-amino-4-methyl-2-methoxycarbonylthiophene with 2-chloropropionyl chloride through simultaneous addition to a reaction mixture containing 3-amino-4-methyl-2-methoxycarbonylthiophene, 2-chloropropionyl chloride and an alkaline component with relative speed which enables to maintain pH of the medium in aqueous phase in the range of 4.0-8.0.

EFFECT: preventing or minimising secondary reactions of alkaline hydrolysis of 2-chloropropionyl chloride during acylation of 3-(2-chloropropionyl)amino-4-methyl-2-methoxycarbonylthiophene and achieving high output and quality of the product, which is used in synthesis of biologically active compounds and is particularly a key intermediate product in synthesis of hydrochloride of methyl ether of 4-methyl-3-[2-(n-propylamin)propionylamino]thiophene-2-carboxylic acid - one of the best local anaesthetics, known as articaine or ultracaine.

1 cl, 1 ex

FIELD: medicine.

SUBSTANCE: invention refers to a compound of formula (I) or to its pharmaceutically acceptable salt: formula (I) wherein; R1 represents hydrogen; R2 represents phenyl, benzothienyl, benzofuranyl or the group -CH2CH2-phenyl; wherein R2 is optionally substituted by 1 or 2 substitutes optionally specified in F, O, Br, I, -CN, -NO2, -OR8, C1-C6alkyl and -N(R9)2; R4 represents phenyl substituted by 1 or 2 substitutes optionally specified in F, CI, Br, I, -CP3, -OH, -OR8 and C1-C6alkyl; each R8 is optionally specified in C1-C6alkyl; and each R9 is optionally specified in H and C1-C6alkyl. The invention also refers to a pharmaceutical composition for activity modulation of depot-controlled calcium channels (SOC-channels) containing such compounds.

EFFECT: there are produced new compounds and based pharmaceutical compositions which can find application in medicine for treating the diseases or conditions, such as rheumatoid arthritis, psoriasis, inflammatory intestinal disease, asthma and multiple sclerosis.

12 cl, 21 dwg, 1 tbl, 14 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel substituted cyclohexylmethyl derivatives, having serotonin, noradrenaline or opioid receptor inhibiting activity, optionally in form of cis- or trans-diastereomers or mixture thereof in form of bases or salts with physiologically compatible acids. In formula (1): R2 denotes H or OH; R1 and R2 together denote or =N-OH, R3 denotes a phenyl residue which is unsubstituted or monosubstituted with a halogen atom or a heteroaryl residue selected from a five-member sulphur-containing heteroaryl such as a thienyl residue or an unsubstituted phenyl residue bonded through a C1-C4alkyl group, R4 and R5 independently denote an unsubstituted C1-C3alkyl or R4 and R5 together denote (CH2)3-6, R8 denotes a linear saturated C1-C4 alkyl group bonded with an aryl, which is unsubstituted or monosubstituted with halogen atoms, R9 denotes a saturated C1-C8alkyl; values of radicals R1, m, n, R6, R7, R10-R13 are given in the claim. The invention also relates to methods of producing compounds of formula (I), a medicinal agent containing said compounds, use of compounds of formula (I) to prepare a medicinal agent for anaesthetic treatment during sharp, neuropathic or chronic pain and for treating depression, urinary incontinence, diarrhoea and alcoholism.

EFFECT: high efficiency of using the compounds.

32 cl, 501 ex, 21 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of general formula

, where X denotes a 5-member heterocylic group bonded through a carbon atom, selected from thiophenyl, furanyl, pyrazolyl and pyrrolyl, which can be substituted with 1-3 Ra groups; T denotes O, S; B is as indicated in the claim; Z1 denotes an unsubstituted cyclopropyl; Z2 denotes a hydrogen atom, C1-C8alkyl; or C1-C8alkoxycarbonyl; Z3 independently denotes a hydrogen atom. The invention also relates to a fungicidal composition containing a compound of formula (I) as an active ingredient, and a plant pathogenic fungus control method in agricultural plants.

EFFECT: obtaining compounds of formula (I), having fungicidal activity.

9 cl, 3 dwg, 255 ex

FIELD: chemistry.

SUBSTANCE: pharmaceutical compositions containing at least one compound of formula (IIIa) or (IIIb) or (IVa) or (IVb), where -X- and Y are described in the claims, or pharmaceutically acceptable salts, esters or amides thereof and a pharmaceutically acceptable carrier, which can be used in processes with modulation or E- and P-selectin expression.

EFFECT: obtaining low-molecular non-glycoside and non-peptide compounds, capable of creating antagonism to selectin-mediated processes.

11 cl, 38 ex, 3 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formulae (1) and (2), where R1 is H or alkyl with 1-6 carbon atoms, R2 is H, alkyl with 1-6 carbon atoms or R1 and R2 together with a nitrogen atom form a saturated or unsaturated 5-, 6- or 7-member ring which can also include one or two heteroatoms independently selected from N, O or S. Said 5-, 6- or 7-member ring is possibly substituted with one or two OH groups or halogen groups, and said 5-, 6- or 7-member ring is possibly condensed with an aromatic or non-aromatic 5- or 6-member ring; R3 is independently selected from H, alkyl with 1-20 carbon atoms, cycloalkyl with 3-6 carbon atoms, phenyl or phenyl-alkyl, where the alkyl group has 1-4 carbon atoms, phenyl(hydroxy)alkyl, where the alkyl group has 1-4 carbon atoms, wherein said phenyl groups are possibly substituted with 1-3 groups independently selected from a group comprising halogen, alkyl with 1-6 carbon atoms, alkoxy with 1-6 carbon atoms, or R3 is CO-R7 or CO-O-R7, where R7 is H, alkyl with 1-20 carbon atoms, optionally substituted with a NH2 group or NH-CO alkyl group, where the alkyl group has 1-6 carbon atoms, phenyl or phenyl-alkyl, where the alkyl group has 1-4 carbon atoms, wherein said phenyl groups are possibly substituted with 1-3 groups independently selected from a group comprising halogen, alkyl with 1-6 carbon atoms, alkoxy with 1-6 carbon atoms, is H, alkyl with 1-6 carbon atoms or CO-R8, where R8 is alkyl with 1-6 carbon atoms; wavy lines denote bonds with carbon atoms, having an R or S configuration; dotted lines denote a bond or absence of a bond provided that the ring containing dotted lines is aromatic; m, n and q are whole numbers independently selected from 0, 1, 2 or 3, provided that the sum of m, n and q equals 2 or 3; s equals 0 or 1; W, X and Y independently denote CH, CR5, CR6 or a heteroatom independently selected from N, O and S, and R5 and R6 are independently selected from H, halogen, alkyl with 1-6 carbon atoms, halogen-substituted alkyl with 1-6 carbon atoms, alkoxy with 1-6 carbon atoms and thioxy with 1-3 carbon atoms, phenyl, or R5 and R6 together with atoms to which they are bonded form a carbocyclic ring which has 6 atoms in the ring, or a heterocyclic ring which has 5 or 6 atoms in the ring and 1-3 heteroatoms independently selected from N, O and S. Said carbocyclic or heterocyclic ring, formed jointly by R5 and R6, is possibly substituted with 1-6 R9 groups, where R9 is a halogen.

EFFECT: higher pain-killing and immune-stimulating action.

65 cl, 1 tbl, 256 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of formula (II-A) or pharmaceutically acceptable salt thereof: [in which symbols denote the following: R10-R12: are identical or different and each denotes halogen, lower alkyl, halogen-lower alkyl, -OR0, -O-halogen-lower alkyl or -CN, R13: R0, halogen, halogen-lower alkyl, -OR0, -O-halogen-lower alkyl or -CN, ring B: benzene ring or a 5-6-member heteroaromatic ring containing 1-2 heteroatoms selected from O, S and N, R14: R0, halogen or -OR0, R0: are identical or different and each denotes H or lower alkyl, Y1: a single bond, lower alkylene, lower alkenylene or O-lower alkylene-, and Z1: -CO2R0 or -C0-NH-SO2-lower alkyl]. The invention also relates to a pharmaceutical composition based on the said compound, having antagonistic effect on the EP1 receptor.

EFFECT: obtaining novel compounds and a pharmaceutical composition based on said compounds, which can be used in a medicinal agent for treating lower urinary tract symptoms.

6 cl, 56 tbl, 231 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to a novel derivative of N-acylanthranilic acid, represented by the following general formula 1, or to its pharmaceutically acceptable salt, in which R1, R2, R3, X1, X2, X3, X4 and A are determined in the invention formula.

EFFECT: invention relates to an inhibitor of collagen production, a medication for treating diseases, associated with the excessive production of collagen, containing N-acylanthranilic acid derivative Formula 1.

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