Synthesis and structure-activity relationship of imidazo(1,2-a)thieno(3,2-e)pyrazines as IKK-beta inhibitors.
The identification of a potent series of IKK-beta selective inhibitors based on an imidazothienopyrazine template and the oral efficacy of one such analog (22j) in the LPS-induced TNF-alpha release mouse model are described.
Belema
Makonen
M
Bristol-Myers Squibb Pharmaceutical Research Institute, 5 Research Parkway, Wallingford, CT 06492, USA. makonen.belema@bms.com
Bunker
Amy
A
Nguyen
Van N
VN
Beaulieu
Francis
F
Ouellet
Carl
C
Qiu
Yuping
Y
Zhang
Yunhui
Y
Martel
Alain
A
Burke
James R
JR
McIntyre
Kim W
KW
Pattoli
Mark A
MA
Daloisio
Connie
C
Gillooly
Kathleen M
KM
Clarke
Wendy J
WJ
Brassil
Patrick J
PJ
Zusi
F Chris
FC
Vyas
Dolatrai M
DM
D000818:Animals; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D051550:I-kappa B Kinase / Q000037:antagonists & inhibitors*; D051379:Mice; D011719:Pyrazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D011719:Pyrazines; D051550:I-kappa B Kinase