22551-91-3Relevant articles and documents
N-(4-acetamidophenyl)-5-acetylfuran-2-carboxamide as a novel orally available diuretic that targets urea transporters with improved PD and PK properties
Wang, Shuyuan,Xu, Yue,Zhao, Yan,Zhang, Shun,Li, Min,Li, Xiaowei,He, Jinzhao,Zhou, Hong,Ge, Zemei,Li, Runtao,Yang, Baoxue
, (2021/10/04)
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.
Synthesis of Furandicarboxylic Acid Esters From Nonfood Feedstocks Without Concomitant Levulinic Acid Formation
van der Klis, Frits,van Haveren, Jacco,van Es, Daan S.,Bitter, Johannes H.
, p. 1460 - 1468 (2017/04/14)
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.
SUBSTITUTED AMIDE COMPOUND
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Page/Page column 24, (2012/07/28)
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.
