- Synthesis and bioevaluation of 1-phenylimidazole-4-carboxylic acid derivatives as novel xanthine oxidoreductase inhibitors
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As part of a continuing study, we designed and synthesized four series of 1-phenylimidazole-4-carboxylic acid derivatives as xanthine oxidoreductase (XOR) inhibitors, evaluated their in vitro inhibitory potencies against XOR and hypouricemic effects in mi
- Li, Jing,Li, Xiaolei,Li, Yuanyuan,Zhang, Lei,Zhou, Haiyan,Zhu, Xinying
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- A method for preparing [...]
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The invention discloses a method for preparing [...], relates to a pharmaceutical technical field of chemical synthesis, comprising the following steps: to adjacent bromobenzylcyanide as raw materials with the isobutyl alcohol in the etherification reaction under alkaline conditions, to obtain 2 - [...]; to hydrogen peroxide/hydrogen bromic acid system for the oxidation of bromide, 2 - [...] oxidation bromination reaction, to obtain 2 - isobuoxy - 5 - bromobenzylcyanide; the 2 - isobuoxy - 5 - bromobenzylcyanide with 2 - boric acid - 4 - methyl - 1, 3 - thiazole - 5 - carboxylic acid ethyl ester in Suziki coupling reaction, to obtain 2 - [3 - cyano - 4 - isobuoxy phenyl] - 4 - methyl thiazole - 5 - carboxylic acid ethyl ester; the 2 - [3 - cyano - 4 - isobuoxy phenyl] - 4 - methyl thiazole - 5 - carboxylic acid ethyl ester under basic condition to obtain [...]. The invention routes and novel and short synthetic route, requires only four-step reaction can be to obtain the target product, used in the preparation raw materials are cheap and easy to obtain, environmental protection, mild reaction conditions, the operation is convenient and controllable, the prepared [...] high purity, high yield.
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Paragraph 0034; 0042; 0046-0047; 0052; 0056-0057; 0062; 0066
(2019/02/13)
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- Phenylimidazole XOR (Xanthine Oxidoreductase) inhibitor and preparation and application thereof
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The invention belongs to the technical field of pharmaceutical and chemical industries and discloses a phenylimidazole XOR (Xanthine Oxidoreductase) inhibitor and the preparation and the application of the phenylimidazole XOR inhibitor. The structure of t
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Paragraph 0070-0072
(2019/09/17)
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- Process Development of Febuxostat Using Palladium- and Copper-Catalyzed C-H Arylation
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There is significant interest in the development of process routes for active pharmaceutical ingredients using C-H arylation methodology. An efficient and practical synthetic route for febuxostat (1), which is the first non-purine-type xanthine oxidase inhibitor, was established via palladium- and copper-catalyzed C-H arylation of thiazole with aryl bromide. The catalyst loading was reduced to 0.1 mol percent for the intermolecular C-H arylation, and a three-step synthesis produced febuxostat in 89percent overall yield with excellent selectivity.
- Dohi, Masahiko,Kato, Yoshiaki,Komiyama, Masato,Kurokawa, Masayuki,Minamizono, Kunio,Sato, Yoshinori,Teramoto, Mitsuru,Tsuchiya, Hideyoshi,Tsuchiya, Naoki,Yajima, Naoki
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p. 1306 - 1311
(2018/09/21)
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- Synthesis and bioevaluation of 1-phenyl-pyrazole-4-carboxylic acid derivatives as potent xanthine oxidoreductase inhibitors
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A diverse library of 1-phenyl-pyrazole-4-carboxylic acid derivatives were synthesized and evaluated for their inhibitory potency against xanthine oxidoreductase (XOR) in vitro and vivo, and the structure-activity relationship (SAR) analyses were also pres
- Li, Jing,Wu, Fangping,Liu, Xingguo,Zou, Yake,Chen, Huixiong,Li, Zheng,Zhang, Lei
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- Facile one-pot transformation of arenes into aromatic nitriles under metal-cyanide-free conditions
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Electron-rich arenes bearing methyl or methoxy groups on the aromatic ring were treated with dichloromethyl methyl ether and ZnBr2, and then with molecular iodine and aq. ammonia to give the corresponding aromatic nitriles in good yields. Using this method, febuxostat was efficiently prepared from 4-bromophenol in four steps. The method can be used for the preparation of aromatic nitriles from arenes in one pot under metal-cyanide-free conditions. Various electron-rich arenes could be effectively converted into the corresponding aromatic nitriles in good yields, by treatment with ZnBr2 and dichloromethyl methyl ether, followed by reaction with molecular iodine and aq. ammonia.
- Tamura, Toshiyuki,Moriyama, Katsuhiko,Togo, Hideo
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p. 2023 - 2029
(2015/03/18)
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- Facile one-pot transformation of phenols into o-cyanophenols
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The treatment of phenols with paraformaldehyde in the presence of MgCl2 and Et3N in THF at 80 C, followed by reaction with molecular iodine and aq. ammonia at room temperature provided the corresponding o-cyanophenols in moderate to good yields. The present reaction is a one-pot transformation of phenols into o-cyanophenols using much less expensive reagents than are typically used; the reaction is free of both transition-metals and cyanide. The utility of this reaction was highlighted during our preparation of Febuxostat from p-bromophenol.
- Nakai, Yuhta,Moriyama, Katsuhiko,Togo, Hideo
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p. 6077 - 6083
(2015/03/30)
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- HTS followed by NMR based counterscreening. Discovery and optimization of pyrimidones as reversible and competitive inhibitors of xanthine oxidase
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The identification of novel, non-purine based inhibitors of xanthine oxidase is described. After a high-throughput screening campaign, an NMR based counterscreen was used to distinguish actives, which interact with XO in a reversible manner, from assay artefacts. This approach identified pyrimidone 1 as a reversible and competitive inhibitor with good lead-like properties. A hit to lead campaign gave compound 41, a nanomolar inhibitor of hXO with efficacy in the hyperuricemic rat model after oral dosing.
- Even?s, Johan,Edfeldt, Fredrik,Lepist?, Matti,Svitacheva, Naila,Synnergren, Anna,Lundquist, Britta,Gr?nse, Mia,R?nnholm, Anna,Varga, Mikael,Wright, John,Wei, Min,Yue, Sherrie,Wang, Junfeng,Li, Chong,Li, Xuan,Chen, Gang,Liao, Yong,Lv, Gang,Tj?rnebo, Ann,Narjes, Frank
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supporting information
p. 1315 - 1321
(2014/03/21)
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- Direct oxidative conversion of methylarenes into aromatic nitriles
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A variety of methylarenes were successfully converted into the corresponding aromatic nitriles in good to moderate yields by the treatment with NBS or DBDMH in the presence of a catalytic amount of AIBN or BPO, followed by the reaction with molecular iodine in aq NH3 in a one-pot procedure. The present reaction is a useful and practical transition-metal-free method for the preparation of aromatic nitriles from methylarenes.
- Tsuchiya, Daisuke,Kawagoe, Yuhsuke,Moriyama, Katsuhiko,Togo, Hideo
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p. 4194 - 4197
(2013/09/12)
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- METHOD FOR PRODUCING PHENYL-SUBSTITUTED HETEROCYCLIC DERIVATIVE BY MEANS OF COUPLING METHOD USING PALLADIUM COMPOUND
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The present invention provides a method for producing a xanthine oxidase inhibitor, which is a therapeutic agent for hyperuricemia, or intermediates of the same, said method being efficient and using a short process. The present invention is a novel coupling method for obtaining a compound represented by formula (3) by bringing about a coupling reaction between a compound represented by formula (1) and a compound represented by formula (2), in the presence of a palladium compound, a ligand capable of coordinating to the palladium compound, a base, a C1-C40 carboxylic acid, and at least one kind of additive.
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Paragraph 0304; 0305; 0306
(2013/06/28)
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- COMPOSITIONS AND THERAPEUTIC USES OF IKK-RELATED KINASE EPSILON AND TANKBINDING KINASE 1 INHIBITORS
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The invention relates to compounds, pharmaceutical compositions and medicaments comprising such compounds, and the use of these compounds, compositions, and medicaments in methods of treating diseases and disorders.
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Page/Page column 65
(2012/11/06)
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- PROCESSES FOR THE PREPARATION OF FEBUXOSTAT AND SALTS THEREOF
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There is provided a process for preparing febuxostat of formula (I) or a pharmaceutically acceptable salt thereof, the process comprising: condensing a compound of formula (A) with a compound of formula (B) to form an ester of febuxostat; hydrolyzing the ester of febuxostat to febuxostat, and optionally converting the febuxostat to a pharmaceutically acceptable salt thereof, wherein: R' is an activating group selected from boronic acid or lithium; R is selected from optionally substituted C1-4 alkyl or optionally substituted aryl; L is a leaving group selected from diazo, halo, -OSO2R", -OCOR" or -O-Si(R")3; and R" is selected from optionally substituted C1-4 alkyl or optionally substituted aryl.
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Page/Page column 26
(2011/07/07)
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- PROCESS FOR PRODUCING PHENYL-SUBSTITUTED HETEROCYCLIC DERIVATIVE THROUGH COUPLING USING TRANSITION METAL CATALYST
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A process for efficiently producing, through few steps either a xanthine oxidase inhibitor, which is a therapeutic agent for hyperuricemia, or an intermediate therefore. The process is a novel coupling process which comprises subjecting a compound represented by formula (1) to coupling reaction with a compound represented by formula (2) in the presence of a transition metal compound to thereby obtain a compound represented by formula (3).
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Page/Page column 17-18
(2012/01/13)
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- 2-PHENYLTHIOPHENE DERIVATIVE
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The present invention relates to a 2-phenylthiophene derivative or a salt thereof, wherein the thiophene ring is substituted with a carboxyl group or the like and the benzene ring has an electron-withdrawing group such as a cyano group and an electron-donating group such as a substituted alkoxy group at the same time. Since the compound of the invention has good xanthine oxidase-inhibitory action and uric acid-lowering action and does not have a structure derived from nucleic acid, the compound has advantages of high safety and excellent effects as compared with conventional compounds and is useful as a therapeutic or preventive agent for hyperuricemia, gout, inflammatory bowel diseases, diabetic kidney diseases, diabetic retinopathy, or the like.
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Page/Page column 16
(2008/06/13)
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- 2-PHENYLPYRIDINE DERIVATIVE
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A 2-phenylpyridine derivative represented by the following general formula (I) or a salt thereof. The compounds have satisfactory xanthine oxidase inhibitory activity and uric acid-lowering activity and are useful as a therapeutic or preventive agent for hyperuricemia, gout, inflammatory intestinal diseases, diabetic nephropathy, diabetic retinopathy, etc. [The symbols in the formula have the following meanings: R1: H, etc.; R2: -CO2H, etc.; R3 and R4: H, etc.; R5: -CN, etc.; R6: H, etc.; X: -O-, -N(R8)-, or -S-; (provided that the groups represented by R5 and -X-R7 are bonded in a meta position or the para position to the pyridyl group) R8: H, etc.; R7: C1-8 linear or branched alkyl, etc.; Y: a bond, etc.; and R9, R10, and R11: H, etc. (provided that when X is -N(R8)-, then R8 may be bonded to R7 to form a nitrogenous saturated heterocycle in cooperation with the adjacent nitrogen atom).]
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Page/Page column 25
(2008/06/13)
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