- COMPOUNDS AND USES THEREOF
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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.
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- Discovery of phenylaminopyridine derivatives as novel HIV-1 non-nucleoside reverse transcriptase inhibitors
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We identified a novel class of aryl-substituted triazine compounds as potent non-nucleoside reverse transcriptase inhibitors (NNRTIs) during a high-throughput screening campaign that evaluated more than 200000 compounds for antihuman immunodeficiency virus (HIV) activity using a cell-based full replication assay. Herein, we disclose the optimization of the antiviral activity in a cell-based assay system leading to the discovery of compound 27, which possessed excellent potency against wild-type HIV-1 (EC50 = 0.2 nM) as well as viruses bearing Y181C and K103N resistance mutations in the reverse transcriptase gene. The X-ray crystal structure of compound 27 complexed with wild-type reverse transcriptase confirmed the mode of action of this novel class of NNRTIs. Introduction of a chloro functional group in the pyrazole moiety dramatically improved hERG and CYP inhibition profiles, yielding highly promising leads for further development.
- Kim, Junwon,Park, Changmin,So, Wonyoung,Jo, Mina,Ok, Taedong,Kwon, Jeongjin,Jo, Suyeon,Choi, Jihyun,Kim, Hyoung Cheul,Lee, Doohyun,Kim, Youngmi,Ko, Yoonae,Choi, Inhee,Kong, Sunju,Park, Youngsam,Yoon, Jaewan,Ju, Moon Kyeong,Kim, Junghwan,Han, Sung-Jun,Kim, Tae-Hee,Cechetto, Jonathan,Nam, Jiyoun,Sommer, Peter,Liuzzi, Michel,Lee, Jinhwa,No, Zaesung
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supporting information
p. 678 - 682,5
(2020/08/31)
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- Discovery of 3-{5-[(6-amino-1H-pyrazolo[3,4-b]pyridine-3-yl)methoxy]-2- chlorophenoxy}-5-chlorobenzonitrile (MK-4965): A potent, orally bioavailable HIV-1 non-nucleoside reverse transcriptase inhibitor with improved potency against key mutant viruses
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Non-nucleoside reverse transcriptase inhibitors (NNRTIs) have been shown to be a key component of highly active antiretroviral therapy (HAART). The use of NNRTIs has become part of standard combination antiviral therapies producing clinical outcomes with
- Tucker, Thomas J.,Sisko, John T.,Tynebor, Robert M.,Williams, Theresa M.,Felock, Peter J.,Flynn, Jessica A.,Lai, Ming-Tain,Liang, Yuexia,McGaughey, Georgia,Liu, Meiquing,Miller, Mike,Moyer, Gregory,Munshi, Vandna,Perlow-Poehnelt, Rebecca,Prasad, Sridhar,Reid, John C.,Sanchez, Rosa,Torrent, Maricel,Vacca, Joseph P.,Wan, Bang-Lin,Yan, Youwei
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experimental part
p. 6503 - 6511
(2009/10/17)
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- HIV reverse transcriptase inhibitors
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Compounds having the structure: are HIV reverse transcriptase inhibitors, wherein A, X, Y, Z, R1 and R2 are defined herein. The compounds and their pharmaceutically acceptable salts are useful in the inhibition of HIV reverse transcriptase, the prophylaxis and treatment of infection by HIV and in the prophylaxis, delay in the onset, and treatment of AIDS. The compounds and their salts can be employed as ingredients in pharmaceutical compositions, optionally in combination with other antivirals, immunomodulators, antibiotics or vaccines.
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Page/Page column 54-55
(2010/11/25)
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