Pyrazinoindolone inhibitors of MAPKAP-K2.
Optimization of pyrazinoindolone inhibitors of MAPKAP-K2 (MK2) provides a reasonable balance of cellular potency and physicochemical properties. Mechanistic studies support the inhibition of MK2 which is responsible for the sub-micromolar cellular efficacy.
Goldberg
D R
DR
Department of Medicinal Chemistry, Boehringer Ingelheim Pharmaceuticals, Inc., Research and Development Center, 900 Ridgebury Road, Ridgefield, CT 06877, USA. dgoldber@rdg.boehringer-ingelheim.com
Choi
Y
Y
Cogan
D
D
Corson
M
M
DeLeon
R
R
Gao
A
A
Gruenbaum
L
L
Hao
M H
MH
Joseph
D
D
Kashem
M A
MA
Miller
C
C
Moss
N
N
Netherton
M R
MR
Pargellis
C P
CP
Pelletier
J
J
Sellati
R
R
Skow
D
D
Torcellini
C
C
Tseng
Y-C
YC
Wang
J
J
Wasti
R
R
Werneburg
B
B
Wu
J P
JP
Xiong
Z
Z
D020650:Combinatorial Chemistry Techniques; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors*; D015394:Molecular Structure; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D000099190:MAP-Kinase-Activated Kinase 2
D004791:Enzyme Inhibitors; D007211:Indoles; D047908:Intracellular Signaling Peptides and Proteins; D017346:Protein Serine-Threonine Kinases; D011720:Pyrazoles; D000099190:MAP-Kinase-Activated Kinase 2