Sulfonamidopyrrolidinone Factor Xa Inhibitors: Potency and Selectivity Enhancements via P-1 and P-4 Optimization was written by Choi-Sledeski, Yong Mi;McGarry, Daniel G.;Green, Daniel M.;Mason, Helen J.;Becker, Michael R.;Davis, Roderick S.;Ewing, William R.;Dankulich, William P.;Manetta, Vincent E.;Morris, Robert L.;Spada, Alfred P.;Cheney, Daniel L.;Brown, Karen D.;Colussi, Dennis J.;Chu, Valeria;Heran, Christopher L.;Morgan, Suzanne R.;Bentley, Ross G.;Leadley, Robert J.;Maignan, Sebastien;Guilloteau, Jean-Pierre;Dunwiddie, Christopher T.;Pauls, Henry W.. And the article was included in Journal of Medicinal Chemistry in 1999.Recommanded Product: 15777-70-5 This article mentions the following:
Sulfonamidopyrrolidinones were previously disclosed as a selective class of factor Xa (fXa) inhibitors, culminating in the identification of RPR120844 as a potent member with efficacy in vivo. Recognizing the usefulness of the central pyrrolidinone template for the presentation of ligands to the S-1 and S-4 subsites of fXa, studies to optimize the P-1 and P-4 groups were initiated. Sulfonamidopyrrolidinones containing 4-hydroxy- and 4-aminobenzamidines were discovered to be effective inhibitors of fXa. X-ray crystallog. experiments in trypsin and mol. modeling studies suggest that our inhibitors bind by insertion of the 4-hydroxybenzamidine moiety into the S-1 subsite of the fXa active site. Of the P-4 groups examined, the pyridylthienyl sulfonamides were found to confer excellent potency and selectivity especially in combination with 4-hydroxybenzamidine. Compound I (RPR130737) was shown to be a potent fXa inhibitor (Ki = 2 nM) with selectivity against structurally related serine proteinases (>1000 times). Preliminary biol. evaluation demonstrates the effectiveness of this inhibitor in common assays of thrombosis in vitro (e.g. activated partial thromboplastin time) and in vivo (e.g. rat FeCl2-induced carotid artery thrombosis model). In the experiment, the researchers used many compounds, for example, 4-Hydroxy-3-methylbenzonitrile (cas: 15777-70-5Recommanded Product: 15777-70-5).
4-Hydroxy-3-methylbenzonitrile (cas: 15777-70-5) belongs to alcohols. Alcohols are among the most common organic compounds. They are used as sweeteners and in making perfumes, are valuable intermediates in the synthesis of other compounds, and are among the most abundantly produced organic chemicals in industry. Converting an alcohol to an alkene requires removal of the hydroxyl group and a hydrogen atom on the neighbouring carbon atom. Dehydrations are most commonly carried out by warming the alcohol in the presence of a strong dehydrating acid, such as concentrated sulfuric acid.Recommanded Product: 15777-70-5
Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts