-transparent.png){kind=logo}
Discovery of Phenylaminopyridine Derivatives as Novel HIV-1 Non-nucleoside Reverse Transcriptase Inhibitors. 2012
Junwon Kim, and
Doohyun Lee, and
Changmin Park, and
Wonyoung So, and
Mina Jo, and
Taedong Ok, and
Jeongjin Kwon, and
Sunju Kong, and
Suyeon Jo, and
Youngmi Kim, and
Jihyun Choi, and
Hyoung Cheul Kim, and
Yoonae Ko, and
Inhee Choi, and
Youngsam Park, and
Jaewan Yoon, and
Moon Kyeong Ju, and
Junghwan Kim, and
Sung-Jun Han, and
Tae-Hee Kim, and
Jonathan Cechetto, and
Jiyoun Nam, and
Peter Sommer, and
Michel Liuzzi, and
Jinhwa Lee, and
Zaesung No
Medicinal Chemistry 2, Medicinal Chemistry 1, Medicinal Chemistry 3, Drug Biology Group, Screening Technology Platforms Group, DMPK Group, Cell Biology of Retroviruses Group, Early Discovery Program, and Late Discovery Program, Institut Pasteur Korea (IP-K) , Sampyeong-dong 696, Bundang-gu, Seongnam-si, Gyeonggi-do 463-400, Republic of Korea.
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.
| UI | MeSH Term | Description | Entries |
|---|
Related Publications
Junwon Kim, and
Doohyun Lee, and
Changmin Park, and
Wonyoung So, and
Mina Jo, and
Taedong Ok, and
Jeongjin Kwon, and
Sunju Kong, and
Suyeon Jo, and
Youngmi Kim, and
Jihyun Choi, and
Hyoung Cheul Kim, and
Yoonae Ko, and
Inhee Choi, and
Youngsam Park, and
Jaewan Yoon, and
Moon Kyeong Ju, and
Junghwan Kim, and
Sung-Jun Han, and
Tae-Hee Kim, and
Jonathan Cechetto, and
Jiyoun Nam, and
Peter Sommer, and
Michel Liuzzi, and
Jinhwa Lee, and
Zaesung No
September 2009,
Bioorganic & medicinal chemistry letters,
Junwon Kim, and
Doohyun Lee, and
Changmin Park, and
Wonyoung So, and
Mina Jo, and
Taedong Ok, and
Jeongjin Kwon, and
Sunju Kong, and
Suyeon Jo, and
Youngmi Kim, and
Jihyun Choi, and
Hyoung Cheul Kim, and
Yoonae Ko, and
Inhee Choi, and
Youngsam Park, and
Jaewan Yoon, and
Moon Kyeong Ju, and
Junghwan Kim, and
Sung-Jun Han, and
Tae-Hee Kim, and
Jonathan Cechetto, and
Jiyoun Nam, and
Peter Sommer, and
Michel Liuzzi, and
Jinhwa Lee, and
Zaesung No
June 2012,
ACS medicinal chemistry letters,
Junwon Kim, and
Doohyun Lee, and
Changmin Park, and
Wonyoung So, and
Mina Jo, and
Taedong Ok, and
Jeongjin Kwon, and
Sunju Kong, and
Suyeon Jo, and
Youngmi Kim, and
Jihyun Choi, and
Hyoung Cheul Kim, and
Yoonae Ko, and
Inhee Choi, and
Youngsam Park, and
Jaewan Yoon, and
Moon Kyeong Ju, and
Junghwan Kim, and
Sung-Jun Han, and
Tae-Hee Kim, and
Jonathan Cechetto, and
Jiyoun Nam, and
Peter Sommer, and
Michel Liuzzi, and
Jinhwa Lee, and
Zaesung No
February 2004,
Journal of medicinal chemistry,
Junwon Kim, and
Doohyun Lee, and
Changmin Park, and
Wonyoung So, and
Mina Jo, and
Taedong Ok, and
Jeongjin Kwon, and
Sunju Kong, and
Suyeon Jo, and
Youngmi Kim, and
Jihyun Choi, and
Hyoung Cheul Kim, and
Yoonae Ko, and
Inhee Choi, and
Youngsam Park, and
Jaewan Yoon, and
Moon Kyeong Ju, and
Junghwan Kim, and
Sung-Jun Han, and
Tae-Hee Kim, and
Jonathan Cechetto, and
Jiyoun Nam, and
Peter Sommer, and
Michel Liuzzi, and
Jinhwa Lee, and
Zaesung No
June 2015,
European journal of medicinal chemistry,
Junwon Kim, and
Doohyun Lee, and
Changmin Park, and
Wonyoung So, and
Mina Jo, and
Taedong Ok, and
Jeongjin Kwon, and
Sunju Kong, and
Suyeon Jo, and
Youngmi Kim, and
Jihyun Choi, and
Hyoung Cheul Kim, and
Yoonae Ko, and
Inhee Choi, and
Youngsam Park, and
Jaewan Yoon, and
Moon Kyeong Ju, and
Junghwan Kim, and
Sung-Jun Han, and
Tae-Hee Kim, and
Jonathan Cechetto, and
Jiyoun Nam, and
Peter Sommer, and
Michel Liuzzi, and
Jinhwa Lee, and
Zaesung No
November 2009,
Archiv der Pharmazie,
Junwon Kim, and
Doohyun Lee, and
Changmin Park, and
Wonyoung So, and
Mina Jo, and
Taedong Ok, and
Jeongjin Kwon, and
Sunju Kong, and
Suyeon Jo, and
Youngmi Kim, and
Jihyun Choi, and
Hyoung Cheul Kim, and
Yoonae Ko, and
Inhee Choi, and
Youngsam Park, and
Jaewan Yoon, and
Moon Kyeong Ju, and
Junghwan Kim, and
Sung-Jun Han, and
Tae-Hee Kim, and
Jonathan Cechetto, and
Jiyoun Nam, and
Peter Sommer, and
Michel Liuzzi, and
Jinhwa Lee, and
Zaesung No
November 2022,
Molecules (Basel, Switzerland),
Junwon Kim, and
Doohyun Lee, and
Changmin Park, and
Wonyoung So, and
Mina Jo, and
Taedong Ok, and
Jeongjin Kwon, and
Sunju Kong, and
Suyeon Jo, and
Youngmi Kim, and
Jihyun Choi, and
Hyoung Cheul Kim, and
Yoonae Ko, and
Inhee Choi, and
Youngsam Park, and
Jaewan Yoon, and
Moon Kyeong Ju, and
Junghwan Kim, and
Sung-Jun Han, and
Tae-Hee Kim, and
Jonathan Cechetto, and
Jiyoun Nam, and
Peter Sommer, and
Michel Liuzzi, and
Jinhwa Lee, and
Zaesung No
February 2017,
Bioorganic chemistry,
Junwon Kim, and
Doohyun Lee, and
Changmin Park, and
Wonyoung So, and
Mina Jo, and
Taedong Ok, and
Jeongjin Kwon, and
Sunju Kong, and
Suyeon Jo, and
Youngmi Kim, and
Jihyun Choi, and
Hyoung Cheul Kim, and
Yoonae Ko, and
Inhee Choi, and
Youngsam Park, and
Jaewan Yoon, and
Moon Kyeong Ju, and
Junghwan Kim, and
Sung-Jun Han, and
Tae-Hee Kim, and
Jonathan Cechetto, and
Jiyoun Nam, and
Peter Sommer, and
Michel Liuzzi, and
Jinhwa Lee, and
Zaesung No
July 2010,
Journal of medicinal chemistry,
Junwon Kim, and
Doohyun Lee, and
Changmin Park, and
Wonyoung So, and
Mina Jo, and
Taedong Ok, and
Jeongjin Kwon, and
Sunju Kong, and
Suyeon Jo, and
Youngmi Kim, and
Jihyun Choi, and
Hyoung Cheul Kim, and
Yoonae Ko, and
Inhee Choi, and
Youngsam Park, and
Jaewan Yoon, and
Moon Kyeong Ju, and
Junghwan Kim, and
Sung-Jun Han, and
Tae-Hee Kim, and
Jonathan Cechetto, and
Jiyoun Nam, and
Peter Sommer, and
Michel Liuzzi, and
Jinhwa Lee, and
Zaesung No
November 2009,
Yao xue xue bao = Acta pharmaceutica Sinica,
Junwon Kim, and
Doohyun Lee, and
Changmin Park, and
Wonyoung So, and
Mina Jo, and
Taedong Ok, and
Jeongjin Kwon, and
Sunju Kong, and
Suyeon Jo, and
Youngmi Kim, and
Jihyun Choi, and
Hyoung Cheul Kim, and
Yoonae Ko, and
Inhee Choi, and
Youngsam Park, and
Jaewan Yoon, and
Moon Kyeong Ju, and
Junghwan Kim, and
Sung-Jun Han, and
Tae-Hee Kim, and
Jonathan Cechetto, and
Jiyoun Nam, and
Peter Sommer, and
Michel Liuzzi, and
Jinhwa Lee, and
Zaesung No
August 2008,
Bioorganic & medicinal chemistry letters,
