- N-(4-acetamidophenyl)-5-acetylfuran-2-carboxamide as a novel orally available diuretic that targets urea transporters with improved PD and PK properties
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Urea transporters (UTs) have been identified as new targets for diuretics. Functional deletion of UTs led to urea-selective urinary concentrating defects with relative salt sparing. In our previous study, a UT inhibitor with a diarylamide scaffold, which is denoted as 11a, was demonstrated as the first orally available UT inhibitor. However, the oral bioavailability of 11a was only 4.38%, which obstructed its clinical application. In this work, by replacing the nitro group of 11a with an acetyl group, 25a was obtained. Compared with 11a, 25a showed a 10 times stronger inhibitory effect on UT-B (0.14 μM vs. 1.41 μM in rats, and 0.48 μM vs. 5.82 μM in mice) and a much higher inhibition rate on UT-A1. Moreover, the metabolic stability both in vitro and in vivo and the drug-like properties (permeability and solubility) of 25a were obviously improved compared with those of 11a. Moreover, the bioavailability of 25a was 15.18%, which was 3 times higher than that of 11a, thereby resulting in significant enhancement of the diuretic activities in rats and mice. 25a showed excellent potential for development as a promising clinical diuretic candidate for targeting UTs to treat diseases that require long-term usage of diuretics, such as hyponatremia.
- Wang, Shuyuan,Xu, Yue,Zhao, Yan,Zhang, Shun,Li, Min,Li, Xiaowei,He, Jinzhao,Zhou, Hong,Ge, Zemei,Li, Runtao,Yang, Baoxue
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- Method for preparing 5-formyl-2-furancarboxylate
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The invention discloses a method for preparing 5-formyl-2-furancarboxylate. The method is characterized in that the 5-formyl-2-furancarboxylate is prepared through a one-step reaction of furoate, usedas a raw material, in a solvent at a temperature of 0-100 DEG C under normal pressure with a Vilsmeier reagent and a Lewis acid as catalysts. The method has the advantages of high selectivity, good atom economy, high product yield, simple process route, and high additional values of the product. The method is harmless to the environment, is suitable for large-scale synthesis, and has a potentialindustrial application prospect.
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Paragraph 0027-0030; 0053-0054
(2020/02/20)
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- Highly efficient and selective oxidation of 5-hydroxymethylfurfural by molecular oxygen in the presence of Cu-MnO2 catalyst
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The selective oxidation of 5-hydroxymethylfurfural (HMF) to produce value-added chemicals is a hot topic in the utilization of biomass, in which the development of heterogeneous catalyst and the use of O2 as terminal oxidant is desired. In this work, a series of metal ion-doped MnO2 materials are successfully prepared using liquid precipitation method, and employed as catalysts for the aerobic oxidation of HMF in the alcoholic solvents. As a result, it is found that 86.0% conversion of HMF and 96.1% selectivity of 2,5-diformylfuran (DFF) was obtained under suitable conditions. Moreover, the Cu-MnO2 catalyst can keep a high activity after being recycled five times.
- Tong, Xinli,Yu, Linhao,Chen, Hui,Zhuang, Xuli,Liao, Shengyun,Cui, Hongge
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- Synthesis of Furandicarboxylic Acid Esters From Nonfood Feedstocks Without Concomitant Levulinic Acid Formation
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5-Hydroxymethylfurfural (HMF) is a versatile intermediate in biomass conversion pathways. However, the notoriously unstable nature of HMF imposes challenges to design selective routes to chemicals such as furan-2,5-dicarboxylic acid (FDCA). Here, a new strategy for obtaining furans is presented, bypassing the formation of the unstable HMF. Instead of starting with glucose/fructose and thus forming HMF as an intermediate, the new route starts from uronic acids, which are abundantly present in many agro residues such as sugar beet pulp, potato pulp, and citrus peels. Conversion of uronic acids, via ketoaldonic acids, to the intermediate formylfuroic acid (FFA) esters, and subsequently to FDCA esters, proceeds without formation of levulinic acid or insoluble humins. This new route provides an attractive strategy to valorize agricultural waste streams and a route to furanic building blocks without the co-production of levulinic acid or humins.
- van der Klis, Frits,van Haveren, Jacco,van Es, Daan S.,Bitter, Johannes H.
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p. 1460 - 1468
(2017/04/14)
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- SUBSTITUTED AMIDE COMPOUND
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A substituted amide compound is useful as an active ingredient of a pharmaceutical composition, in particular a pharmaceutical composition for treating diseases caused by lysophosphatidic acid (LPA). The compound is of a formula: In this formula, A is an optionally substituted aryl, etc.; B is an optionally substituted 5-membered aromatic hetero ring group; X is a single bond or —(CRX1RX2)n—; n is 1, 2, 3, or 4; RX1 and RX2 are hydrogen, etc.; Y1 to Y5 are each CRY or N; each RY is hydrogen, etc.; R1 and R2 are hydrogen, etc.; m is 1, 2, or 3; R3 is hydrogen, etc.; and R4 is an optionally substituted lower alkyl, etc.
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Page/Page column 24
(2012/07/28)
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- A new synthesis of 8-oxabicyclo[3.2.1]octan-2-one and its use for the preparation of cycloheptane annulated furans
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Two novel syntheses of 8-oxabicyclo[3.2.1]octan-2-one are described, making this key intermediate readily available in preparative amounts. On chain elongation with various oxophosphonates this compound is converted to α,β-unsaturated ketones, which, on t
- Hopf, Henning,Abhilash
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scheme or table
p. 3349 - 3351
(2010/03/04)
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- Heterocyclic indole derivatives and mono- or diazaindole derivatives
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There is provided a compound represented by the general formula (1): wherein Het represents an optionally substituted heterocyclic group; A1and A2each independently represent —CH═, etc.; A3represents —CH2—, etc.; R1represents a 4-fluorophenyl group, etc.; R2represents an alkyl group; n represents 0, 1 or 2, provided that when A1and A2both are —CH═, A3represents —CH2— or —SO2—, which is an indole derivative or a mono- or diazaindole derivative that has COX-2 inhibitory activity and is useful as a pharmaceutical, such as an anti-inflammatory agent, or addition salts thereof with a pharmaceutically acceptable acid or base, or hydrates thereof.
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Page column 55
(2008/06/13)
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- HETEROCYCLIC INDOLE DERIVATIVES AND MONO- OR DIAZAINDOLE DERIVATIVES
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Indole derivatives and mono- or diazaindole derivatives represented by general formula (1), pharmaceutically acceptable acid-addition salts or base-addition salts thereof or hydrates of the same which have a COX-2 inhibitory activity and are useful as drugs such as anti-inflammatory agents, wherein Het represents an optionally substituted heterocycle; A1 and A2 independently represent each -CH=, etc.; A3 represents -CH2-, etc.; R1 represents 4-fluorophenyl, etc.; R2 represents alkyl; and n is 0, 1 or 2, provided that when A1 and A2 are both -CH=, then A3 is -CH2- or -SO2-.
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- Reaction of ethyl ester and nitrile of 5-methyl-2-furancarboxylic acid with mixture of nitric and sulfuric acids
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The reaction of 70% HNO3 with ethyl 5-methyl-2- furancarboxylate in concentrated H2SO4 gave the corresponding 4-nitro derivative and ethyl 5-formyl-2-furancarboxylate. Only 4-nitro derivative, which was converted into amid
- Saldabol,Slavinskaya,Popelis,Mazheika
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p. 134 - 136
(2007/10/03)
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- Phosphorylamides, their preparation and use
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A phosphorylamide derivative represented by the general formula (I): STR1 wherein R represents an amino group that may be substituted, or a salt thereof, possesses potent antibacterial activity against Helicobacter bacterium, especially Helicobacter pylori, and is useful for prevention or treatment of digestive diseases caused by Helicobacter bacterium, solely or in combination with an antacid or an acid secretion inhibitor.
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- Disubstituted aryl and heteroaryl imines having retinoid-like biological activity
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Compounds of the formula STR1 wherein the R 1 groups independently are hydrogen, lower alkyl, or two geminal R 1 groups jointly represent an oxo ( O) or a thio ( S) group; R 2 is hydrogen or lower alkyl, or halogen; M is or --N CR 4 -- or --R 4 C N-- where R 4 is hydrogen or lower alkyl; X is C(R 1) 2 ; Y is phenyl optionally substituted with an R 3 group which is lower alkyl or halogen; A is (CH 2) n where n is 0-5, lower branched chain alkyl, cycloalkyl, alkenyl, alkynyl; B is hydrogen, COOH or a pharmaceutically acceptable salt thereof, COOR 8, CONR 9 R 10, --CH 2 OH, CH 2OR 11, CH 2 OCOR 11, CHO, CH(OR 12) 2, CHOR 13 O, --COR 7, CR 7 (OR 12) 2, or CR 7 OR 13 O, where R 7 is an alkyl, cycloalkyl or alkenyl group containing 1 to 5 carbons, R 8 is an alkyl group of 1 to 10 carbons, or a cycloalkyl group of 5 to 10 carbons, or R 8 is phenyl or lower alkylphenyl, R 9 and R 10 independently are hydrogen, an alkyl group of 1 to 10 carbons, or a cycloalkyl group of 5-10 carbons, or phenyl or lower alkylphenyl, R 11 is lower alkyl, phenyl or lower alkylphenyl, R 12 is lower alkyl, and R 13 is divalent alkyl radical of 2-5 carbons have retinoid-like biological activity.
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- Naphthenic and heterocyclic retinoic acid analogues
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Naphthenic and heterocyclic retinoic acid analogues such as (E)-6-[2-(2,6,6-trimethyl-1-cyclohexen-1-yl)ethenyl]-2-naphthaldehyde, methyl 6-[2-(2,6,6-trimethyl-1-cyclohexen-1-yl)ethenyl]-2-naphthoate, 6-[2-(2,6,6-trimethyl-1-cyclohexen-1-yl)ethenyl]-2-nap
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- Aromatic Retinoic Acid Analogues. 2. Synthesis and Pharmacological Activity
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Aromatic analogues of (E)-1-(4-carboxyphenyl)-2-methyl-4-(2,6,6-trimethyl-1-cyclohexen-1-yl)butadiene (1b) and its ethyl ester (1a) were synthesized as potential chemopreventive agents for the treatment of epithelial cancer and such skin diseases as psoriasis and cystic acne.The phenyl ring of 1 was replaced by 2-fluorophenyl, 2-methoxyphenyl, thienyl, furanyl, and pyridyl groups.The 1-fluorobutadiene analogue of 1 was also synthesized.With exception for the furanyl analogue, these compounds demonstrated good activity in reversing keratinization in hamster tracheal organ culture and in inhibiting the induction of ornithine decarboxylase in mouse epidermis by a tumor promoter.
- Dawson, Marcia I.,Chan, Rebecca,Hobbs, Peter D.,Chao, Wan-ru,Schiff, Leonard J.
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p. 1282 - 1293
(2007/10/02)
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