-transparent.png){kind=logo}
Design of annulated pyrazoles as inhibitors of HIV-1 reverse transcriptase. 2008
Zachary K Sweeney, and
Seth F Harris, and
Seth F Arora, and
Hassan Javanbakht, and
Yu Li, and
Jennifer Fretland, and
James P Davidson, and
J Roland Billedeau, and
Shelley K Gleason, and
Donald Hirschfeld, and
Joshua J Kennedy-Smith, and
Taraneh Mirzadegan, and
Ralf Roetz, and
Mark Smith, and
Sarah Sperry, and
Judy M Suh, and
Jeffrey Wu, and
Stan Tsing, and
Armando G Villaseñor, and
Amber Paul, and
Guoping Su, and
Gabrielle Heilek, and
Julie Q Hang, and
Amy S Zhou, and
Jesper A Jernelius, and
Fang-Jie Zhang, and
Klaus Klumpp
Department of Medicinal Chemistry, Roche Palo Alto LLC, 3431 Hillview Avenue, Palo Alto, California 94304, USA. zachary.sweeney@roche.com
Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are recommended components of preferred combination antiretroviral therapies used for the treatment of HIV. These regimens are extremely effective in suppressing virus replication. Structure-based optimization of diaryl ether inhibitors led to the discovery of a new series of pyrazolo[3,4-c]pyridazine NNRTIs that bind the reverse transcriptase enzyme of human immunodeficiency virus-1 (HIV-RT) in an expanded volume relative to most other inhibitors in this class.The binding mode maintains the beta13 and beta14 strands bearing Pro236 in a position similar to that in the unliganded reverse transcriptase structure, and the distribution of interactions creates the opportunity for substantial resilience to single point mutations. Several pyrazolopyridazine NNRTIs were found to be highly effective against wild-type and NNRTI-resistant viral strains in cell culture.
Related Publications
Zachary K Sweeney, and
Seth F Harris, and
Seth F Arora, and
Hassan Javanbakht, and
Yu Li, and
Jennifer Fretland, and
James P Davidson, and
J Roland Billedeau, and
Shelley K Gleason, and
Donald Hirschfeld, and
Joshua J Kennedy-Smith, and
Taraneh Mirzadegan, and
Ralf Roetz, and
Mark Smith, and
Sarah Sperry, and
Judy M Suh, and
Jeffrey Wu, and
Stan Tsing, and
Armando G Villaseñor, and
Amber Paul, and
Guoping Su, and
Gabrielle Heilek, and
Julie Q Hang, and
Amy S Zhou, and
Jesper A Jernelius, and
Fang-Jie Zhang, and
Klaus Klumpp
June 2007,
Applied microbiology and biotechnology,
Zachary K Sweeney, and
Seth F Harris, and
Seth F Arora, and
Hassan Javanbakht, and
Yu Li, and
Jennifer Fretland, and
James P Davidson, and
J Roland Billedeau, and
Shelley K Gleason, and
Donald Hirschfeld, and
Joshua J Kennedy-Smith, and
Taraneh Mirzadegan, and
Ralf Roetz, and
Mark Smith, and
Sarah Sperry, and
Judy M Suh, and
Jeffrey Wu, and
Stan Tsing, and
Armando G Villaseñor, and
Amber Paul, and
Guoping Su, and
Gabrielle Heilek, and
Julie Q Hang, and
Amy S Zhou, and
Jesper A Jernelius, and
Fang-Jie Zhang, and
Klaus Klumpp
May 2020,
ACS medicinal chemistry letters,
Zachary K Sweeney, and
Seth F Harris, and
Seth F Arora, and
Hassan Javanbakht, and
Yu Li, and
Jennifer Fretland, and
James P Davidson, and
J Roland Billedeau, and
Shelley K Gleason, and
Donald Hirschfeld, and
Joshua J Kennedy-Smith, and
Taraneh Mirzadegan, and
Ralf Roetz, and
Mark Smith, and
Sarah Sperry, and
Judy M Suh, and
Jeffrey Wu, and
Stan Tsing, and
Armando G Villaseñor, and
Amber Paul, and
Guoping Su, and
Gabrielle Heilek, and
Julie Q Hang, and
Amy S Zhou, and
Jesper A Jernelius, and
Fang-Jie Zhang, and
Klaus Klumpp
August 2013,
Organic and medicinal chemistry letters,
Zachary K Sweeney, and
Seth F Harris, and
Seth F Arora, and
Hassan Javanbakht, and
Yu Li, and
Jennifer Fretland, and
James P Davidson, and
J Roland Billedeau, and
Shelley K Gleason, and
Donald Hirschfeld, and
Joshua J Kennedy-Smith, and
Taraneh Mirzadegan, and
Ralf Roetz, and
Mark Smith, and
Sarah Sperry, and
Judy M Suh, and
Jeffrey Wu, and
Stan Tsing, and
Armando G Villaseñor, and
Amber Paul, and
Guoping Su, and
Gabrielle Heilek, and
Julie Q Hang, and
Amy S Zhou, and
Jesper A Jernelius, and
Fang-Jie Zhang, and
Klaus Klumpp
January 2008,
Advances in pharmacology (San Diego, Calif.),
Zachary K Sweeney, and
Seth F Harris, and
Seth F Arora, and
Hassan Javanbakht, and
Yu Li, and
Jennifer Fretland, and
James P Davidson, and
J Roland Billedeau, and
Shelley K Gleason, and
Donald Hirschfeld, and
Joshua J Kennedy-Smith, and
Taraneh Mirzadegan, and
Ralf Roetz, and
Mark Smith, and
Sarah Sperry, and
Judy M Suh, and
Jeffrey Wu, and
Stan Tsing, and
Armando G Villaseñor, and
Amber Paul, and
Guoping Su, and
Gabrielle Heilek, and
Julie Q Hang, and
Amy S Zhou, and
Jesper A Jernelius, and
Fang-Jie Zhang, and
Klaus Klumpp
January 2000,
Advances in pharmacology (San Diego, Calif.),
Zachary K Sweeney, and
Seth F Harris, and
Seth F Arora, and
Hassan Javanbakht, and
Yu Li, and
Jennifer Fretland, and
James P Davidson, and
J Roland Billedeau, and
Shelley K Gleason, and
Donald Hirschfeld, and
Joshua J Kennedy-Smith, and
Taraneh Mirzadegan, and
Ralf Roetz, and
Mark Smith, and
Sarah Sperry, and
Judy M Suh, and
Jeffrey Wu, and
Stan Tsing, and
Armando G Villaseñor, and
Amber Paul, and
Guoping Su, and
Gabrielle Heilek, and
Julie Q Hang, and
Amy S Zhou, and
Jesper A Jernelius, and
Fang-Jie Zhang, and
Klaus Klumpp
June 1995,
Journal of medicinal chemistry,
Zachary K Sweeney, and
Seth F Harris, and
Seth F Arora, and
Hassan Javanbakht, and
Yu Li, and
Jennifer Fretland, and
James P Davidson, and
J Roland Billedeau, and
Shelley K Gleason, and
Donald Hirschfeld, and
Joshua J Kennedy-Smith, and
Taraneh Mirzadegan, and
Ralf Roetz, and
Mark Smith, and
Sarah Sperry, and
Judy M Suh, and
Jeffrey Wu, and
Stan Tsing, and
Armando G Villaseñor, and
Amber Paul, and
Guoping Su, and
Gabrielle Heilek, and
Julie Q Hang, and
Amy S Zhou, and
Jesper A Jernelius, and
Fang-Jie Zhang, and
Klaus Klumpp
December 2013,
Organic and medicinal chemistry letters,
Zachary K Sweeney, and
Seth F Harris, and
Seth F Arora, and
Hassan Javanbakht, and
Yu Li, and
Jennifer Fretland, and
James P Davidson, and
J Roland Billedeau, and
Shelley K Gleason, and
Donald Hirschfeld, and
Joshua J Kennedy-Smith, and
Taraneh Mirzadegan, and
Ralf Roetz, and
Mark Smith, and
Sarah Sperry, and
Judy M Suh, and
Jeffrey Wu, and
Stan Tsing, and
Armando G Villaseñor, and
Amber Paul, and
Guoping Su, and
Gabrielle Heilek, and
Julie Q Hang, and
Amy S Zhou, and
Jesper A Jernelius, and
Fang-Jie Zhang, and
Klaus Klumpp
June 2008,
Virus research,
Zachary K Sweeney, and
Seth F Harris, and
Seth F Arora, and
Hassan Javanbakht, and
Yu Li, and
Jennifer Fretland, and
James P Davidson, and
J Roland Billedeau, and
Shelley K Gleason, and
Donald Hirschfeld, and
Joshua J Kennedy-Smith, and
Taraneh Mirzadegan, and
Ralf Roetz, and
Mark Smith, and
Sarah Sperry, and
Judy M Suh, and
Jeffrey Wu, and
Stan Tsing, and
Armando G Villaseñor, and
Amber Paul, and
Guoping Su, and
Gabrielle Heilek, and
Julie Q Hang, and
Amy S Zhou, and
Jesper A Jernelius, and
Fang-Jie Zhang, and
Klaus Klumpp
January 1992,
Journal of enzyme inhibition,
Zachary K Sweeney, and
Seth F Harris, and
Seth F Arora, and
Hassan Javanbakht, and
Yu Li, and
Jennifer Fretland, and
James P Davidson, and
J Roland Billedeau, and
Shelley K Gleason, and
Donald Hirschfeld, and
Joshua J Kennedy-Smith, and
Taraneh Mirzadegan, and
Ralf Roetz, and
Mark Smith, and
Sarah Sperry, and
Judy M Suh, and
Jeffrey Wu, and
Stan Tsing, and
Armando G Villaseñor, and
Amber Paul, and
Guoping Su, and
Gabrielle Heilek, and
Julie Q Hang, and
Amy S Zhou, and
Jesper A Jernelius, and
Fang-Jie Zhang, and
Klaus Klumpp
December 2012,
Journal of medicinal chemistry,
