A di (pyrimidine nucleoside 5'-)polyphosphate of Formula I (see formula I) is synthesized by converting a pyrimidine nucleoside 5'-triphosphate into a pyrimidine nucleoside 5'-cyclic triphosphate by use of a condensing agent, and subsequently reacting the pyrimidine nucleoside 5'-cyclic triphosphate with a pyrimidine nucleotide in the presence of a salt of a metal selected from among magnesium, manganese, and iron. Through the method of the invention, a di(pyrimidine nucleoside 5'-)polyphosphate can be synthesized from an unprotected pyrimidine nucleoside 5'-phosphate serving as a starting material at a synthesis yield of 50% or higher. Therefore, the method of the invention is suitable for large-scale synthesis of a di(pyrimidine nucleoside 5')polyphosphate.
Among commonly known 3',3'-cGAMP is a lyophilized product. The lyophilized product needs a lyophilizer during the manufacture. This, itself, causes a limitation in scale-up for mass production. Thus, it has been desired to develop and obtain a large amount of their crystals in a simple manner without using a special apparatus such as a lyophilizer. In addition, conventionally known lyophilized products or ethanol precipitates are highly hygroscopic. Hence, the present invention addresses the problem of providing an easy-to-handle crystal with excellent shelf life. A hydrate crystal of 3',3'-cGAMP according to the invention may be either a crystal of alkali metal salt or a crystal of free acid. Either is less hygroscopic than existing powder. Thus, each is easy to handle in various purposes and is thus useful as a pharmaceutical raw material or the like.
A61K 31/7084 - Composés ayant deux nucléosides ou nucléotides, p. ex. dinucléotide de la nicotinamide-adénine, dinucléotide de la flavine-adénine
A61K 39/39 - Préparations médicinales contenant des antigènes ou des anticorps caractérisées par les additifs immunostimulants, p. ex. par les adjuvants chimiques
C07H 21/02 - Composés contenant au moins deux unités mononucléotide comportant chacune des groupes phosphate ou polyphosphate distincts liés aux radicaux saccharide des groupes nucléoside, p. ex. acides nucléiques avec le ribosyle comme radical saccharide
3.
CROSSLINKED NUCLEOSIDE INTERMEDIATE CRYSTAL AND METHOD FOR PRODUCING SAME, AND METHOD FOR PRODUCING CROSSLINKED NUCLEOSIDE AMIDITE
Disclosed herein is a crystal of a compound represented by the formula 5 in which R1 represents a protecting group for a hydroxyl group which is 4-halobenzyl group or 4- nitrobenzyl group, and R2 represents a leaving group which is 4-toluenesulfonyloxy group, methanesulfonyloxy group, chloromethanesulfonyloxy group, trifluoromethanesulfonyloxy group or halogeno group. Methods for producing a crystal of a compound represented by formula 5 are also disclosed. The described crystal is useful as a crosslinked nucleoside intermediate capable of being stably stored for a long period of time.
The invention provides a method for producing 3'- phosphoadenosine 5'-phosphosulfate (PAPS), the method including subjecting ATP to sulfation and phosphorylation by use of adenosine 5'-triphosphate sulfurylase (ATPS) and adenosine 5'-phosphosulfate kinase (APSK), wherein an adenosine 5'-triphosphate (ATP) supply/regeneration system including adenosine 5'-monophosphate (AMP), polyphosphate, polyphosphate-driven nucleoside 5'-diphosphate kinase (PNDK), and polyphosphate:AMP phosphotransferase (PAP), or an adenosine 5'-triphosphate (ATP) supply/regeneration system including adenosine 5'-monophosphate (AMP), polyphosphate, polyphosphate-driven nucleoside 5'-diphosphate kinase (PNDK), and adenylate kinase (ADK) is employed instead of ATP.
C12P 19/32 - Nucléotides avec un système cyclique condensé, contenant un cycle à six chaînons, comportant deux atomes d'azote dans le même cycle, p. ex. nucléotides puriques, dinucléotide de la nicotinamide-adénine
5.
METHOD FOR PRODUCING P1,P4-DI(URIDINE 5'-)TETRAPHOSPHATE
A method for producing P1,P4-di(uridine 5'-)tetraphosphate (UP4U) is developed, which does not require the use of free UTP and does not undergo the decrease in synthesis efficiency. A method for producing UP4U, characterized by reacting a phosphoric-acid-activating compound represented by formula [II] or [III] with a phosphoric acid compound selected from the group consisting of UMP, UDP, UTP and pyrophosphoric acid or a salt thereof (excluding free UTP) in water or a hydrophilic organic solvent in the presence of a metal ion selected from the group consisting of an iron (II) ion, an iron (III) ion, a trivalent aluminum ion, a trivalent lanthanum ion and a trivalent cerium ion. (Each of R1, X and n in formula [II] and X in formula [III] is as defined in claim 1.)
A61K 31/7072 - Composés ayant des radicaux saccharide et des hétérocycles ayant l'azote comme hétéro-atome d'un cycle, p. ex. nucléosides, nucléotides contenant des cycles à six chaînons avec l'azote comme hétéro-atome d'un cycle contenant des pyrimidines condensées ou non-condensées ayant des groupes oxo liés directement au cycle pyrimidine, p. ex. cytidine, acide cytidylique ayant deux groupes oxo liés directement au cycle pyrimidine, p. ex. uridine, acide uridylique, thymidine, zidovudine
A61K 31/7105 - Acides ribonucléiques naturels, c.-à-d. contenant uniquement des riboses liés à l'adénine, la guanine, la cytosine ou l'uracile et ayant des liaisons 3'-5' phosphodiester
A61P 11/00 - Médicaments pour le traitement des troubles du système respiratoire
The present invention provides a 4'-C-substituted-2--haloadenosine derivative represented by the following formula [I], [II], or [III]: (see formula I)(see formula II)(see formula III) (wherein X represents a halogen atom, R1 represents an ethynyl group or a cyano group, and R2 represents hydrogen, a phosphate residue, or a phosphate derivative residue). The present invention also provides a pharmaceutical composition containing the derivative and a pharmaceutically acceptable carrier therefor.
A61K 31/7076 - Composés ayant des radicaux saccharide et des hétérocycles ayant l'azote comme hétéro-atome d'un cycle, p. ex. nucléosides, nucléotides contenant des cycles à six chaînons avec l'azote comme hétéro-atome d'un cycle contenant des pyrimidines condensées ou non-condensées contenant des purines, p. ex. adénosine, acide adénylique
The present invention provides a method for enzymatically producing uridine 5'-diphospho-N-acetylgalactosamine (UDP-GalNAc) (which is an important substrate for oligosaccharide synthesis) from uridine 5'-triphosphate (UTP) and N-acetylgalactosamine 1-phosphate (GalNAc 1-P), the method including using, as an enzyme, uridine 5'-diphospho-N-acetylglucosamine pyrophosphorylase (UDP-GlcNAc pyrophosphorylase) derived from a microorganism (exclusive of a pathogenic microorganism). The GalNAc 1-P employed can be prepared from N-acetylgalactosamine and a phosphate donor in a reaction system by use of N-acetylgalactosamine kinase. According to the present invention, uridine 5'-diphospho-N-acetylgalactosamine can be efficiently produced by use of a relatively inexpensive substrate.
A signal processing device is composed of a signal acquisition unit and a signal processing unit. The signal acquisition unit acquires a signal corresponding to a vibration propagated from a string attached to a stringed instrument from a pickup element that picks up the signal corresponding to the vibration. The signal processing unit includes a filter that performs convolution operation using a filter coefficient set in the filter, the signal processing unit applying the convolution operation to the acquired signal through the filter and outputting a processed signal. The filter is set with the filter coefficient corresponding to a transfer function which has a frequency response developing a plurality of peak waveforms corresponding to resonance of a body of another stringed instrument different from the stringed instrument within a specific frequency range and which allows components of the peak waveforms to decay more rapidly than a component of a fundamental sound in the vibration of the string in the processed signal.
G10H 3/12 - Instruments dans lesquels les sons sont produits par des moyens électromécaniques utilisant des générateurs résonnants mécaniques, p. ex. des cordes ou des instruments à percussion, dont les sons sont captés par des transducteurs électromécaniques, les signaux électriques étant alors traités ou amplifiés puis convertis en ondes sonores au moyen d'un haut-parleur ou d'un dispositif équivalent
G10L 19/02 - Techniques d'analyse ou de synthèse de la parole ou des signaux audio pour la réduction de la redondance, p. ex. dans les vocodeursCodage ou décodage de la parole ou des signaux audio utilisant les modèles source-filtre ou l’analyse psychoacoustique utilisant l'analyse spectrale, p. ex. vocodeurs à transformée ou vocodeurs à sous-bandes
A signal processing device is composed of an acquiring unit, a filter unit and a changing unit. The acquiring unit acquires a signal indicating vibration of a string. The filter unit performs convolution operation on the signal acquired by the acquiring unit according to a filter coefficient and outputs a resulting signal. The filter coefficient is set such that the resulting signal has a frequency response containing a plurality of peak waveforms associated with resonance of a body of a stringed instrument within a specific frequency range. The changing unit changes the filter coefficient so as to change a peak value of each of the peak waveforms while maintaining a width of each of the peak waveforms in the frequency response.
G10H 3/12 - Instruments dans lesquels les sons sont produits par des moyens électromécaniques utilisant des générateurs résonnants mécaniques, p. ex. des cordes ou des instruments à percussion, dont les sons sont captés par des transducteurs électromécaniques, les signaux électriques étant alors traités ou amplifiés puis convertis en ondes sonores au moyen d'un haut-parleur ou d'un dispositif équivalent
G10L 19/02 - Techniques d'analyse ou de synthèse de la parole ou des signaux audio pour la réduction de la redondance, p. ex. dans les vocodeursCodage ou décodage de la parole ou des signaux audio utilisant les modèles source-filtre ou l’analyse psychoacoustique utilisant l'analyse spectrale, p. ex. vocodeurs à transformée ou vocodeurs à sous-bandes
A crystal of free acid of 3',5'-cyclic diguanylic acid containing no metal salt with cobalt, magnesium or the like is provided. A method is sought for obtaining said crystal in a large amount and with ease. By a manufacturing method comprising a step of adding acid to an aqueous solution of 3',5'-cyclic diguanylic acid so as to lower pH to 1 to 3, crystals
of 3',5'-cyclic diguanylic acid can be obtained in a large amount with ease. Said crystals are free acid crystals which do not contain a metal salt with cobalt, magnesium or the like.
Heretofore, 3',5'-cyclicdiadenylic acid has been provided only in a lyophilized form. The present invention provides a solid form, other than a lyophilized form, of 3',5'-cyclicdiadenylic acid and a method for producing the solid form. An inclusion compound of 3',5'-cyclicdiadenylic acid can be produced by a step of adding an acid to an aqueous 3',5'-cyclicdiadenylic acid solution to decrease the pH value of the solution to 1 to 3. The production method is quite easy to carry out and does not require the use of a special machine or the like.
C07H 1/00 - Procédés de préparation des dérivés du sucre
C07H 21/02 - Composés contenant au moins deux unités mononucléotide comportant chacune des groupes phosphate ou polyphosphate distincts liés aux radicaux saccharide des groupes nucléoside, p. ex. acides nucléiques avec le ribosyle comme radical saccharide
12.
METHOD FOR PURIFYING P1,P4-DI(URIDINE 5'-)TETRAPHOSPHATE
Provided is a simple and practical method for removing iron ions, as a method for purifying P1,P4-di(uridine 5'-)tetraphosphate from a solution that contains iron ions. This method for purifying P1,P4-di(uridine 5'-)tetraphosphate by removing iron ions from an aqueous solution or hydrophilic solvent solution containing P1,P4-di(uridine 5'-)tetraphosphate and iron ions includes: (1) a column purification step that uses a chelate resin, and (2) a step for adjusting the pH of the solution to 5.5 or less following the chelate resin column purification, and then crystallizing P1,P4-di(uridine 5'-)tetraphosphate; or a step for treating the solution with zinc chloride-activated activated carbon following the chelate resin column purification.
A61K 31/7105 - Acides ribonucléiques naturels, c.-à-d. contenant uniquement des riboses liés à l'adénine, la guanine, la cytosine ou l'uracile et ayant des liaisons 3'-5' phosphodiester
A lyophilized product of cyclic-di-AMP requires special production equipment and is thus not suitable for large-scale production. Crystals of cyclic-di-AMP free acid are unstable under severe conditions at 105.degree.C. Then, the present invention addresses the problem of providing a cyclic-di-AMP (Formula I) crystal that can be easily acquired in a large amount and is very stable under the severe conditions at 105.degree.C. Crystals of c-di-AMP sodium salt according to the present invention are extremely stable even under the severe conditions at 105.degree.C. Further, the crystals of c-di-AMP sodium salt according to the present invention can be prepared in a large amount by a simple process including adjusting a c -di-AMP aqueous solution at pH 5.2-12.0 and then adding an organic solvent thereto.(see formula I)
C07H 21/02 - Composés contenant au moins deux unités mononucléotide comportant chacune des groupes phosphate ou polyphosphate distincts liés aux radicaux saccharide des groupes nucléoside, p. ex. acides nucléiques avec le ribosyle comme radical saccharide
NATIONAL UNIVERSITY CORPORATION TOKAI NATIONAL HIGHER EDUCATION AND RESEARCH SYSTEM (Japon)
Inventeur(s)
Ueno, Yoshihito
Abrégé
Provided is a nucleoside derivative represented by the following formula (1): (IMAGE HERE) , or a salt thereof, wherein R1 represents an alkoxy group, a hydrogen atom or a halogen atom; R2 and R4, which may be the same as or different from each other, each represents a hydrogen atom, a protective group for a hydroxyl group, a phosphate group, a protected phosphate group, or -P(=O)nR5R6 in which n represents 0 or 1, R5 and R6, which may be the same as or different from each other, each represents a hydrogen atom, a hydroxyl group, a protected hydroxyl group, a mercapto group, a protected mercapto group, an alkoxy group, a cyanoalkoxy group, an amino group, or a substituted amino group, provided that when n is 1, both R5 and R6 cannot be the hydrogen atom at the same time; R3 represents ?(CH2)mNHR7 in which m represents an integer of 1 to 6, R7 represents a hydrogen atom, an alkyl group, an alkenyl group or a protective group for an amino group; and B represents a purin-9-yl group, a 2-oxo-pyrimidin-1-yl group, a substituted purin-9-yl group, or a substituted 2-oxo-pyrimidin-1-yl group.
C07H 19/20 - Radicaux purine avec le radical saccharide estérifié par des acides phosphoriques ou polyphosphoriques
C07H 21/00 - Composés contenant au moins deux unités mononucléotide comportant chacune des groupes phosphate ou polyphosphate distincts liés aux radicaux saccharide des groupes nucléoside, p. ex. acides nucléiques
C12N 15/113 - Acides nucléiques non codants modulant l'expression des gènes, p. ex. oligonucléotides anti-sens
brevets
