- Polycyclic pyridine oxime-based compound as well as pharmaceutical composition and application thereof
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The invention discloses a polycyclic pyridine oxime-based compound and a pharmaceutical composition and application thereof, wherein the polycyclic pyridine oxime-based compound is shown as a formula (I). The compound shows strong inhibition of influenza
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- Purification and characterization of molybdenum-containing aldehyde dehydrogenase that oxidizes benzyl maltol derivative from Pseudomonas nitroreducens SB32154
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Maltol derivatives are used in a variety of fields due to their metal-chelating abilities. In the previous study, it was found that cytochrome P450 monooxygenase, P450nov, which has the ability to effectively convert the 2-methyl group in a maltol derivative, transformed 3-benzyloxy-2-methyl-4-pyrone (BMAL) to 2-(hydroxymethyl)-3-(phenylmethoxy)-4H-pyran-4-one (BMAL-OH) and slightly to 3-benzyloxy-4-oxo-4 H-pyran-2-carboxaldehyde (BMAL-CHO). We isolated Pseudomonas nitroreducens SB32154 with the ability to convert BMAL-CHO to BMAL-COOH from soil. The enzyme responsible for aldehyde oxidation, a BMAL-CHO dehydrogenase, was purified from P. nitroreducens SB32154 and characterized. The purified BMAL-CHO dehydrogenase was found to be a xanthine oxidase family enzyme with unique structure of heterodimer composed of 75 and 15 kDa subunits containing a molybdenum cofactor and [Fe-S] clusters, respectively. The enzyme showed broad substrate specificity toward benzaldehyde derivatives. Furthermore, one-pot conversion of BMAL to BMAL-COOH via BMAL-CHO by the combination of the BMAL-CHO dehydrogenase with P450nov was achieved.
- Hibi, Makoto,Kozono, Iori,Ogawa, Jun,Takeuchi, Michiki
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p. 2390 - 2400
(2020/08/05)
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- PYRIDOPYRAZINE AND PYRIDOTRIAZINE INHIBITORS OF INFLUENZA VIRUS REPLICATION
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Provided herein are compounds that can inhibit the replication of influenza viruses, reduce the amount of influenza viruses, and/or treat influenza. (I)
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- Spiro pyridone derivative and application
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The invention discloses a spiro pyridone derivative which has a structure shown in a general formula I in the specification. Researches show that the spiro pyridinone derivative has a relatively strong inhibition effect on the activity of influenza A virus RNA polymerase, and can be applied to the preparation of influenza A virus RNA polymerase activity inhibition and influenza A resistance medicines. The general formula I is shown in the specification.
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- Pyridone [1, 2-b] [1,5] triazepine derivatives as well as preparation and application thereof (by machine translation)
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The invention discloses a hydroxypyridone [1, a-b] [1,5] triazepine derivatives as well as preparation and application thereof. Experiments prove that the hydroxypyridinone [1, 2-b] [1,triazepine derivatives (general formula I) have a good inhibition effect on the RNA polymerase activity of influenza A virus RNA, and can be used as an influenza virus RNA polymerase inhibitor to treat influenza caused by influenza virus. General Formula I is as follows. (by machine translation)
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- STEREOSELECTIVE PROCESS FOR PREPARING SUBSTITUTED POLYCYCLIC PYRIDONE DERIVATIVES
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The present invention provides industrially suitable processes for preparing intermediates in the production of substituted polycyclic pyridone derivatives having a cap-dependent endonuclease inhibitory activity. In the process as shown below, wherein each symbol is as defined in the specification, an optically active substituted tricyclic pyridone derivative of the formula (VII) is obtained in high yield and high enantioselectivity by subjecting a compound of the formula (III) or (VI) to intramolecular cyclization with controlling stereochemistry to obtain a compound of the formula (IV) having a removable functional group on an asymmetric carbon, and then removing the functional group thereof.
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- Intermediate and preparation method thereof
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The invention provides a compound as shown in a formula (III). R in the formula is hydrogen atom or hydroxyl protective group. The invention further provides a preparation method of the compound shownin the formula (III), and a preparation method of the compound shown in a formula (I). The compound shown in a formula (IV) is treated as a starting raw material and is reacted with DMF-DMA to obtainthe compound shown in the formula (III); the compound shown in the formula (III) is oxidized to obtain the compound shown in the formula (I). According to the preparation method, raw materials are low in price and easy to obtain; the conditions are mild and are easy to control; the yield is high; few three wastes are generated; massive industrial production can be carried out.
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Paragraph 0075-0077
(2019/07/04)
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- Practical and Scalable Synthetic Method for Preparation of Dolutegravir Sodium: Improvement of a Synthetic Route for Large-Scale Synthesis
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A practical and scalable synthetic method to obtain dolutegravir sodium (1) was established starting from the readily accessible material maltol (2). This synthetic method includes a scalable oxidation process of maltol and palladium-catalyzed amidation for introduction of an amide moiety, leading to a practical manufacturing method in short synthetic steps. The synthetic method demonstrated herein enables multikilogram scale manufacturing of 1 of high purity.
- Aoyama, Yasunori,Hakogi, Toshikazu,Fukui, Yuki,Yamada, Daisuke,Ooyama, Takao,Nishino, Yutaka,Shinomoto, Shoji,Nagai, Masahiko,Miyake, Naoki,Taoda, Yoshiyuki,Yoshida, Hiroshi,Yasukata, Tatsuro
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p. 558 - 564
(2019/04/30)
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- Preparation method of baloxavir marboxil intermediate compound
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The invention relates to a preparation method of a baloxavir marboxil intermediate compound. The preparation method includes: using 2-methyl-3-benzyloxy-4-oxo-4-hydropyrane as the initial raw materialand oxygen as the oxidizing agent to perform oxidizing
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Paragraph 0033-0038; 0045-0048; 0050-0053
(2019/10/17)
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- Hydroxypyridinone and 5-Aminolaevulinic Acid Conjugates for Photodynamic Therapy
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Photodynamic therapy (PDT) is a promising treatment strategy for malignant and nonmalignant lesions. 5-Aminolaevulinic acid (ALA) is used as a precursor of the photosensitizer, protoporphyrin IX (PpIX), in dermatology and urology. However, the effectiveness of ALA-PDT is limited by the relatively poor bioavailability of ALA and rapid conversion of PpIX to haem. The main goal of this study was to prepare and investigate a library of single conjugates designed to coadminister the bioactive agents ALA and hydroxypyridinone (HPO) iron chelators. A significant increase in intracellular PpIX levels was observed in all cell lines tested when compared to the administration of ALA alone. The higher PpIX levels observed using the conjugates correlated well with the observed phototoxicity following exposure of cells to light. Passive diffusion appears to be the main mechanism for the majority of ALA-HPOs investigated. This study demonstrates that ALA-HPOs significantly enhance phototherapeutic metabolite formation and phototoxicity.
- Battah, Sinan,Hider, Robert C.,MacRobert, Alexander J.,Dobbin, Paul S.,Zhou, Tao
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p. 3498 - 3510
(2017/05/05)
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- Intermediate of these pyridonecarboxylic carbamoylalkanoic and HIV integrase inhibitor
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A synthesis approach providing an early ring attachment via a bromination to compound I-I yielding compound II-II: whereby a final product such as AA: can be synthesized. In particular, the 2,4-difluorophenyl-containing sidechain is attached before creation of the additional ring Q.
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- PROCESS FOR THE PREPARATION OF INTERMEDIATE OF DOLUTEGRAVIR
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The present invention provides a novel processes for preparation of methyl 3- (benzyloxy)-5-(2,4-difluorobenzylcarbamoyl)-4-oxo-l-(2-oxoethyl)-l,4-dihydropyiridine-2- carboxylate using novel intermediates.
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- Synthesis, physico-chemical properties, and antimicrobial evaluation of a new series of iron(III) hexadentate chelators
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A series of related 3-hydroxypyridin-4-one hexadentate ligands have been synthesized. These chelators were found to possess a high affinity for iron(III), with a pFe value of about 30. As iron is a critical element to the survival of bacteria, these chelators were predicted to inhibit the growth of bacteria by disrupting bacterial iron absorption. Indeed, they were demonstrated to possess appreciable inhibitory activity against both Gram-positive and Gram-negative bacteria, and therefore, they have potential as antimicrobial agents. 1c and 1g were found to be particularly effective against Gram-negative species. Graphical Abstract: A series of related 3-hydroxypyridin-4-one hexadentate ligands have been synthesized. These chelators were found to possess a high affinity for iron(III), and exhibit appreciable inhibitory activity against both Gram-positive and Gram-negative bacteria, and therefore, they have potential as antimicrobial agents. [Figure not available: see fulltext.]
- Xie, Yuan-Yuan,Liu, Mu-Song,Hu, Pan-Pan,Kong, Xiao-Le,Qiu, Di-Hong,Xu, Ji-Lin,Hider, Robert C.,Zhou, Tao
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p. 2351 - 2359
(2013/07/26)
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- MALTOL ETHER PROCESSES AND INTERMEDIATES
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Novel processes and intermediates are provided according to the general reaction scheme: Formula I, II, III, IV (I), (II), (III), (IV) utilizing a ruthenium catalyst in an oxidative cleavage of the triene 4 whereby an aldehyde may be produced and optionally taken on to a carboxylic acid 5: Formula V (V)
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Page/Page column 13-14
(2010/07/02)
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- PROCESSES AND INTERMEDIATES FOR CARBAMOYLPYRIDONE HIV INTEGRASE INHIBITORS
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Processes are provided which create an aldehyde methylene, or hydrated or hemiacetal methylene attached to a heteroatom of a 6 membered ring without going through an olefinic group and without the necessity of using an osmium reagent. In particular, a comopound of formula (I) can be produced from (II) and avoid the use of an allyl amine: (formulae I and II) where R, P 1 P3, R3 and Rx are as described herein.
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Page/Page column 28-29
(2010/07/02)
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- MULTIDENTATE PYRONE-DERIVED CHELATORS FOR MEDICINAL IMAGING AND CHELATION
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Provided herein are chelating agents and metal chelates that are useful in diagnostic and therapeutic applications. The uses of metal chelates provided herein include their use as contrast agents in medical imaging modalities, such as magnetic resonance imaging (MRI).
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Page/Page column 21
(2008/06/13)
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- POLYCYCLIC CARBAMOYLPYRIDONE DERIVATIVE HAVING HIV INTEGRASE INHIBITORY ACTIVITY
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The present invention is to provide a novel compound (I), having the anti-virus activity, particularly the HIV integrase inhibitory activity, and a drug containing the same, particularly an anti-HIV drug, as well as a process and an intermediate thereof. Compound (I) wherein Z1 is NR4; R1 is hydrogen or lower alkyl; X is a single bond, a hetero atom group selected from O, S, SO, SO2 and NH, or lower alkylene or lower alkenylene in which the hetero atom group may intervene; R2 is optionally substituted aryl; R3 is hydrogen, a halogen, hydroxy, optionally substituted lower alkyl etc; and R4 and Z2 part taken together forms a ring, to form a polycyclic compound, including e.g., a tricyclic or tetracyclic compound.
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- Tris(pyrone) chelates of Gd(III) as high solubility MRI-CA
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Two tripodal, hexadentate pyrone-based chelators have been prepared. These ligands form stable, soluble complexes with gadolinium(III). The complexes show aqueous stability comparable to that of [Gd(DTPA)]2- at pH 7.4. Evaluation by relaxometry shows that these complexes have two inner-sphere water molecules and a very fast water exchange rate. The solution behavior of these complexes suggests that they may be attractive as high relaxivity, next-generation magnetic resonance imaging contrast agents. Copyright
- Puerta, David T.,Botta, Mauro,Jocher, Christoph J.,Werner, Eric J.,Avedano, Stefano,Raymond, Kenneth N.,Cohen, Seth M.
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p. 2222 - 2223
(2007/10/03)
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- ANTIVIRAL AGENT
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The present invention provides an integrase inhibitor. The inventors have have found the following compound of formula (I) possessing an integrase inhibitory activity. (wherein, R C and R D taken together with the neighboring carbon atoms form a ring which may be a condensed ring, Y is hydroxy, mercapto or amino; Z is O, S or NH ; R A is a group shown by (wherein, C ring is N-containing aromatic heterocycle) or the like)
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Page 209; 210
(2010/02/06)
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- The monoethyl ester of meconic acid is an active site inhibitor of HCV NS5B RNA-dependent RNA polymerase
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Screening of the in-house sample collection for compounds with HCV NS5B RNA dependent RNA polymerase inhibition led to the identification of a new lead. Afterwards, we discovered that the screening lead, rather than containing the expected structure 1, was comprised of roughly a 1:1 mixture of meconic acid 2 and its monoethyl ester 3, with all inhibitory potency residing with 3. We propose that this compound shares critical common features for activity with α,γ-diketoacids inhibitors previously discovered by our group. SAR around this molecule will be presented to provide an improved basis for structure-based ligand design.
- Pace, Paola,Nizi, Emanuela,Pacini, Barbara,Pesci, Silvia,Matassa, Victor,De Francesco, Raffaele,Altamura, Sergio,Summa, Vincenzo
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p. 3257 - 3261
(2007/10/03)
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