Discovery of Novel, Potent Inhibitors of Hydroxy Acid Oxidase 1 (HAO1) Using DNA-Encoded Chemical Library Screening was written by Lee, Esther C. Y.;McRiner, Andrew J.;Georgiadis, Katy E.;Liu, Julie;Wang, Zooey;Ferguson, Andrew D.;Levin, Benjamin;von Rechenberg, Moritz;Hupp, Christopher D.;Monteiro, Michael I.;Keefe, Anthony D.;Olszewski, Allison;Eyermann, Charles J.;Centrella, Paolo;Liu, Yanbin;Arora, Shilpi;Cuozzo, John W.;Zhang, Ying;Clark, Matthew A.;Huguet, Christelle;Kohlmann, Anna. And the article was included in Journal of Medicinal Chemistry in 2021.Category: ethers-buliding-blocks This article mentions the following:
Inhibition of hydroxy acid oxidase 1 (HAO1) is a strategy to mitigate the accumulation of toxic oxalate that results from reduced activity of alanine-glyoxylate aminotransferase (AGXT) in primary hyperoxaluria 1 (PH1) patients. DNA-Encoded Chem. Library (DECL) screening provided two novel chem. series of potent HAO1 inhibitors, represented by compounds 3-6. Compound I was further optimized via various structure-activity relationship (SAR) exploration methods to II, a compound with improved potency and absorption, distribution, metabolism, and excretion (ADME)/pharmacokinetic (PK) properties. Since carboxylic acid-containing compounds are often poorly permeable and have potential active glucuronide metabolites, we undertook a brief, initial exploration of acid replacements with the aim of identifying non-acid-containing HAO1 inhibitors. Structure-based drug design initiated with Compound I led to the identification of a nonacid inhibitor of HAO1, III, which has weaker potency and increased permeability. In the experiment, the researchers used many compounds, for example, 3-Formyl-2-methoxyphenylboronic acid (cas: 480424-49-5Category: ethers-buliding-blocks).
3-Formyl-2-methoxyphenylboronic acid (cas: 480424-49-5) belongs to ethers. Ether is less polar than esters, alcohols or amines because of the oxygen atom that is unable to participate in hydrogen bonding due to the presence of bulky alkyl groups on both sides of the oxygen atom. Ethers feature bent C–O–C linkages. In dimethyl ether, the bond angle is 111° and C–O distances are 141 pm. The barrier to rotation about the C–O bonds is low. The bonding of oxygen in ethers, alcohols, and water is similar. In the language of valence bond theory, the hybridization at oxygen is sp3.Category: ethers-buliding-blocks
Referemce:
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem