773-91-1Relevant articles and documents
Potent 1,2,4-Triazino[5,6 b]indole-3-thioether Inhibitors of the Kanamycin Resistance Enzyme Eis from Mycobacterium tuberculosis
Ngo, Huy X.,Green, Keith D.,Gajadeera, Chathurada S.,Willby, Melisa J.,Holbrook, Selina Y. L.,Hou, Caixia,Garzan, Atefeh,Mayhoub, Abdelrahman S.,Posey, James E.,Tsodikov, Oleg. V.,Garneau-Tsodikova, Sylvie
, p. 1030 - 1040 (2018)
A common cause of resistance to kanamycin (KAN) in tuberculosis is overexpression of the enhanced intracellular survival (Eis) protein. Eis is an acetyltransferase that multiacetylates KAN and other aminoglycosides, rendering them unable to bind the bacterial ribosome. By high-throughput screening, a series of substituted 1,2,4-triazino[5,6b]indole-3-thioether molecules were identified as effective Eis inhibitors. Herein, we purchased 17 and synthesized 22 new compounds, evaluated their potency, and characterized their steady-state kinetics. Four inhibitors were found not only to inhibit Eis in vitro, but also to act as adjuvants of KAN and partially restore KAN sensitivity in a Mycobacterium tuberculosis KAN-resistant strain in which Eis is upregulated. A crystal structure of Eis in complex with a potent inhibitor and CoA shows that the inhibitors bind in the aminoglycoside binding site snugly inserted into a hydrophobic cavity. These inhibitors will undergo preclinical development as novel KAN adjuvant therapies to treat KAN-resistant tuberculosis.
Organocatalytic Asymmetric Synthesis of Cyclic Acetals with Spirooxindole Skeleton
Shikari, Amit,Mandal, Koushik,Chopra, Deepak,Pan, Subhas Chandra
supporting information, p. 58 - 63 (2021/11/09)
An organocatalytic asymmetric synthesis of cyclic acetal with spirooxindole skeleton has been developed via a domino reaction between isatin and γ-hydroxy enones. Bifunctional squaramide catalyst with adamantyl motif was found to be the most effective for the cascade reaction. With 10 mol% of the catalyst, the desired products were obtained in 1.8:1 to 9:1 diastereo- and 86% to >99% enantioselectivities from a range of substituted isatins and γ-hydroxy enones. (Figure presented.).
Decarboxylative Organocatalyzed Addition Reactions of Fluoroacetate Surrogates for the Synthesis of Fluorinated Oxindoles
Zetschok, Dominik,Heieck, Lukas,Wennemers, Helma
supporting information, p. 1753 - 1757 (2021/03/08)
Fluorinated malonic acid half thioesters (F-MAHTs) were used as thioester enolate equivalents in organocatalyzed addition reactions to isatins. The products from a range of different N-protected and nonprotected isatins were obtained under mild reaction conditions in high yields and enantioselectivities. The unique reactivity of the thioester moiety enabled diverse derivatization and allowed for the straightforward access to a fluorinated analogue of the anticancer agent (S)-YK-4-279, a therapeutically active compound against Ewing's sarcoma.
A new asymmetric activation strategy for hydrazones as acyl anion equivalents in the bimetallic catalyzed carbonyl-ene reaction
Hu, Wen-Bo,Song, Xixi,Wang, Min-Can
, p. 2055 - 2062 (2021/03/16)
A new asymmetric activation strategy for hydrazones as acyl anion equivalents is developed in the bimetallic catalyzed carbonyl-ene reaction of isatins and hydrazones. Under mild conditions, optically active functionalized 3-hydroxy-2-oxindoles were furnished in up to 98% yield with up to 97% enantioselectivity. In this process, formaldehydetert-butylhydrazone which is seldom employed in asymmetric carbonyl-ene reactions accelerated by a metallic catalyst can be activated well by a Br?nsted base. A possible catalytic cycle is proposed.
