Inhibition of eEF2-K by thieno[2,3-b]pyridine analogues.
Several series of thieno[2-3-b]pyridine analogues were synthesized and screened for inhibitory activity against eukaryotic elongation factor-2 kinase (eEF2-K). Modifications around several regions of the lead molecules were made, with a ring fusion adjacent to the nitrogen on the thienopyridine core being critical for activity. The most active compound 34 shows an IC(50) of 170 nM against eEF2-K in vitro.
Lockman
Jeffrey W
JW
Department of Medicinal Chemistry, Myriad Pharmaceuticals, 305 Chipeta Way, Salt Lake City, UT 84108, United States. jeffrey.lockman@myriadpharma.com
Reeder
Matthew D
MD
Suzuki
Kazuyuki
K
Ostanin
Kirill
K
Hoff
Ryan
R
Bhoite
Leena
L
Austin
Harry
H
Baichwal
Vijay
V
Adam Willardsen
J
J
D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D054736:Elongation Factor 2 Kinase / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D011725:Pyridines / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D011725:Pyridines; C446540:thienopyridine; D054736:Elongation Factor 2 Kinase