850223-53-9Relevant academic research and scientific papers
COMPOUNDS AND USES THEREOF
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Page/Page column 110; 111, (2020/10/20)
The present invention features compounds useful in the treatment of neurological disorders and primary brain cancer. The compounds of the invention, alone or in combination with other pharmaceutically active agents, can be used for treating or preventing neurological disorders and primary brain cancer.
COMPOUNDS AND USES THEREOF
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Page/Page column 103-104, (2019/10/15)
The present invention features compounds useful in the treatment of neurological disorders. The compounds of the invention, alone or in combination with other pharmaceutically active agents, can be used for treating or preventing neurological disorders.
Quinolone carboxylic acids as a novel monoketo acid class of human immunodeficiency virus type 1 integrase inhibitors
Sato, Motohide,Kawakami, Hiroshi,Motomura, Takahisa,Aramaki, Hisateru,Matsuda, Takashi,Yamashita, Masaki,Ito, Yoshiharu,Matsuzaki, Yuji,Yamataka, Kazunobu,Ikeda, Satoru,Shinkai, Hisashi
supporting information; experimental part, p. 4869 - 4882 (2010/03/02)
Human immunodeficiency virus type 1 (HIV-1) integrase is a crucial target for antiretroviral drugs, and several keto - enol acid class (often referred to as diketo acid class) inhibitors have clinically exhibited-marked antiretroviral activity. Here, we show the synthesis and the detailed structure - activity relationship of the quinolone carboxylic acids as a novel monoketo acid class of integrase inhibitors. 6-(3-Chloro-2-fluorobenzyl)-1-((2S)-1-hydroxy-3,3- dimethylbutan-2-yl)-7-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid 51, which showed an IC50 of 5.8 nMin the strand transfer assay and an ED50 of 0.6 nMin the antiviral assay, and 6-(3-chloro-2-fluorobenzyl) -1-((2S)-1-hydroxy-3-methylbutan-2-yl)-7-methoxy-4-oxo-1,4-dihydroquinoline-3- carboxylic acid 49, which had an IC50 of 7.2 nMand an ED50 of 0.9 nM, were the most potent compounds in this class. The monoketo acid 49 was much more potent at inhibiting integrasecatalyzed strand transfer processes than 3′-processing reactions, as is the case with the keto - enol acids. Elvitegravir 49 was chosen as a candidate for further studies and is currently in phase 3 clinical trials.
