6345-08-0Relevant articles and documents
Analogues of the Herbicide, N-Hydroxy- N-isopropyloxamate, Inhibit Mycobacterium tuberculosis Ketol-Acid Reductoisomerase and Their Prodrugs Are Promising Anti-TB Drug Leads
Kandale, Ajit,Patel, Khushboo,Hussein, Waleed M.,Wun, Shun Jie,Zheng, Shan,Tan, Lendl,West, Nicholas P.,Schenk, Gerhard,Guddat, Luke W.,McGeary, Ross P.
, p. 1670 - 1684 (2021/02/27)
New drugs to treat tuberculosis (TB) are urgently needed to combat the increase in resistance observed among the current first-line and second-line treatments. Here, we propose ketol-acid reductoisomerase (KARI) as a target for anti-TB drug discovery. Twenty-two analogues of IpOHA, an inhibitor of plant KARI, were evaluated as antimycobacterial agents. The strongest inhibitor of Mycobacterium tuberculosis (Mt) KARI has a Ki value of 19.7 nM, fivefold more potent than IpOHA (Ki = 97.7 nM). This and four other potent analogues are slow- and tight-binding inhibitors of MtKARI. Three compounds were cocrystallized with Staphylococcus aureus KARI and yielded crystals that diffracted to 1.6-2.0 ? resolution. Prodrugs of these compounds possess antimycobacterial activity against H37Rv, a virulent strain of human TB, with the most active compound having an MIC90 of 2.32 ± 0.04 μM. This compound demonstrates a very favorable selectivity window and represents a highly promising lead as an anti-TB agent.
Direct C3 Carbamoylation of 2H-Indazoles
Bhat, Vighneshwar Shridhar,Lee, Anna
supporting information, p. 3382 - 3385 (2021/06/28)
We developed a novel method for direct C3 carbamoylation of 2H-indazoles using oxamic acids as carbamoyl radical sources. In the presence of ammonium persulfate, carbamoyl radicals were generated from oxamic acids, then used for further reactions with 2H-indazoles to afford the desired products. The reaction proceeds under metal- and catalyst-free conditions. This simple process allows for the efficient synthesis of C3 carbamoylated 2H-indazoles, which are important scaffolds in organic synthesis.
Urethanes synthesis from oxamic acids under electrochemical conditions
Ogbu, Ikechukwu Martin,Lusseau, Jonathan,Kurtay, Gülbin,Robert, Frédéric,Landais, Yannick
supporting information, p. 12226 - 12229 (2020/10/26)
Urethane synthesis via oxidative decarboxylation of oxamic acids under mild electrochemical conditions is reported. This simple phosgene-free route to urethanes involves an in situ generation of isocyanates by anodic oxidation of oxamic acids in an alcoholic medium. The reaction is applicable to a wide range of oxamic acids, including chiral ones, and alcohols furnishing the desired urethanes in a one-pot process without the use of a chemical oxidant.
