SAR and in vivo evaluation of 4-aryl-2-aminoalkylpyrimidines as potent and selective Janus kinase 2 (JAK2) inhibitors
著者
和文:
Timothy Forsyth,
Patrick C. Kearney,
Byung Gyu Kim,
Henry W. B. Johnson,
Naing Aay,
Arlyn Arcalas,
David S. Brown,
Vicky Chan,
Jeff Chen,
Hongwang Du,
Sergey Epshteyn,
Adam A. Galan,
Tai P. Huynh,
Mohamed A. Ibrahim,
Brian Kane,
Elena S. Koltun,
Grace Mann,
Lisa E. Meyr,
Matthew S. Lee,
Gary L. Lewis,
Robin T. Noguchi,
Michael Pack,
Brian H. Ridgway,
Xian Shi,
TAKEUCHI CRAIG,
Peiwen Zu,
James W. Leahy,
John M. Nuss,
Ron Aoyama,
Stefan Engst,
Steven B. Gendreau,
Robert Kassees,
Jia Li,
Shwu-Hwa Lin,
Jean-Francois Martini,
Thomas Stout,
Philip Tong,
John Woolfrey,
Wentao Zhang,
Peiwen Yu.
英文:
Timothy Forsyth,
Patrick C. Kearney,
Byung Gyu Kim,
Henry W. B. Johnson,
Naing Aay,
Arlyn Arcalas,
David S. Brown,
Vicky Chan,
Jeff Chen,
Hongwang Du,
Sergey Epshteyn,
Adam A. Galan,
Tai P. Huynh,
Mohamed A. Ibrahim,
Brian Kane,
Elena S. Koltun,
Grace Mann,
Lisa E. Meyr,
Matthew S. Lee,
Gary L. Lewis,
Robin T. Noguchi,
Michael Pack,
Brian H. Ridgway,
Xian Shi,
Craig Takeuchi,
Peiwen Zu,
James W. Leahy,
John M. Nuss,
Ron Aoyama,
Stefan Engst,
Steven B. Gendreau,
Robert Kassees,
Jia Li,
Shwu-Hwa Lin,
Jean-Francois Martini,
Thomas Stout,
Philip Tong,
John Woolfrey,
Wentao Zhang,
Peiwen Yu.
We report the discovery of a series of 4-aryl-2-aminoalkylpyrimidine derivatives as potent and selectiveJAK2 inhibitors. High throughput screening of our in-house compound library led to the identification ofhit 1, from which optimization resulted in the discovery of highly potent and selective JAK2 inhibitors.Advanced lead 10d demonstrated a significant dose-dependent pharmacodynamic and antitumor effectin a mouse xenograft model. Based upon the desirable profile of 10d (XL019) it was advanced into clinicaltrials.
ヘルプ