Synthesis, initial SAR and biological evaluation of 1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridin-4-amine derived inhibitors of IkappaB kinase.
A new series of tricyclic-based inhibitors of IKK have been derived from an earlier lead compound. The synthesis and structure-activity relationships (SAR) are described. Compound 4k inhibited TNF production in rats stimulated with LPS.
Bristol-Myers Squibb Research and Development, Princeton, NJ 08543-4000, USA. james.kempson@bms.com
James
J
Kempson
Junqing
J
Guo
Jagabandhu
J
Das
Robert V
RV
Moquin
Steven H
SH
Spergel
Scott H
SH
Watterson
Charles M
CM
Langevine
Alaric J
AJ
Dyckman
Mark
M
Pattoli
James R
JR
Burke
Xiaoxia
X
Yang
Kathleen M
KM
Gillooly
Kim W
KW
McIntyre
Laishun
L
Chen
John H
JH
Dodd
Murray
M
McKinnon
Joel C
JC
Barrish
William J
WJ
Pitts
D000818:Animals; D051550:I-kappa B Kinase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007093:Imidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D007093:Imidazoles; D008070:Lipopolysaccharides; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D014409:Tumor Necrosis Factor-alpha; D051550:I-kappa B Kinase