1016758-32-9Relevant academic research and scientific papers
Discovery of a Novel Mycobacterial F-ATP Synthase Inhibitor and its Potency in Combination with Diarylquinolines
Anbarasu, Sivaraj,Bates, Roderick W.,Dick, Thomas,Dr?ge, Peter,Grüber, Gerhard,Harikishore, Amaravadhi,Hotra, Adam,Kalia, Nitin Pal,Kalyanasundaram, Revathy,Lakshmanan, Umayal,Makhija, Harshyaa,Ng, Pearly Shuyi,Parthasarathy, Krupakar,Pethe, Kevin,Poulsen, Anders,Pradeep, Chaudhari Namrata,Ragunathan, Priya,Sae-Lao, Patcharaporn,Sarathy, Jickky Palmae,Saw, Wuan-Geok,Seankongsuk, Pattarakiat,Shin, Joon,Tan, Jocelyn Hui Ling
, p. 13295 - 13304 (2020/06/03)
The F1FO-ATP synthase is required for growth and viability of Mycobacterium tuberculosis and is a validated clinical target. A mycobacterium-specific loop of the enzyme's rotary γ subunit plays a role in the coupling of ATP synthesis within the enzyme complex. We report the discovery of a novel antimycobacterial, termed GaMF1, that targets this γ subunit loop. Biochemical and NMR studies show that GaMF1 inhibits ATP synthase activity by binding to the loop. GaMF1 is bactericidal and is active against multidrug- as well as bedaquiline-resistant strains. Chemistry efforts on the scaffold revealed a dynamic structure activity relationship and delivered analogues with nanomolar potencies. Combining GaMF1 with bedaquiline or novel diarylquinoline analogues showed potentiation without inducing genotoxicity or phenotypic changes in a human embryonic stem cell reporter assay. These results suggest that GaMF1 presents an attractive lead for the discovery of a novel class of anti-tuberculosis F-ATP synthase inhibitors.
Design, synthesis and structure-activity relationship studies of novel sirtuin 2 (SIRT2) inhibitors with a benzamide skeleton
Sakai, Taki,Matsumoto, Yotaro,Ishikawa, Minoru,Sugita, Kazuyuki,Hashimoto, Yuichi,Wakai, Nobuhiko,Kitao, Akio,Morishita, Era,Toyoshima, Chikashi,Hayashi, Tomoatsu,Akiyama, Tetsu
, p. 328 - 339 (2015/03/03)
Human sirtuin 2 (SIRT2) is an attractive target molecule for development of drugs to treat neurodegenerative diseases and cancer, because SIRT2 inhibitors have a protective effect against neurodegeneration and an anti-proliferative effect on cancer stem c
DI(HETERO)ARYLAMIDES AND SULFONAMIDES, METHODS FOR THEIR PREPARATION AND THERAPEUTIC USES THEREOF
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Page/Page column 48; 49; 50, (2015/02/25)
The present invention refers to compounds of formula (I): as well as to a method for their preparation, pharmaceutical compositions comprising the same, and use thereof for the treatment and/or prevention of conditions associated with the alteration of the activity of β-galactosidase, specially galactosidase beta-1 or GLB1, including GM1 gangliosidoses and Morquio syndrome, type B.
ANTI-VIRAL COMPOUNDS
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Page/Page column 143, (2010/11/27)
Compounds effective in inhibiting replication of Hepatitis C virus ("HCV") or other viruses are disclosed. This invention is also directed to compositions comprising such compounds, co-formulation or co-administration of such compounds with other anti-viral or therapeutic agents, processes and intermediates for the syntheses of such compounds, and methods of using such compounds for the treatment of HCV or other viral infections.
