Discovery and optimization of p38 inhibitors via computer-assisted drug design.
Integration of computational methods, X-ray crystallography, and structure-activity relationships will be disclosed, which lead to a new class of p38 inhibitors that bind to p38 MAP kinase in a Phe out conformation.
Department of Medicinal Chemistry, Boehringer Ingelheim Pharmaceuticals, Inc., Research and Development Center, Ridgefield, Connecticut 06877, USA. dgoldber@rdg.boehringer-ingelheim.com
Daniel R
DR
Goldberg
Ming-Hong
MH
Hao
Kevin C
KC
Qian
Alan D
AD
Swinamer
Donghong A
DA
Gao
Zhaoming
Z
Xiong
Chris
C
Sarko
Angela
A
Berry
John
J
Lord
Ronald L
RL
Magolda
Tazmeen
T
Fadra
Rachel R
RR
Kroe
Alison
A
Kukulka
Jeffrey B
JB
Madwed
Leslie
L
Martin
Christopher
C
Pargellis
Donna
D
Skow
Jinhua J
JJ
Song
Zhulin
Z
Tan
Carol A
CA
Torcellini
Clare S
CS
Zimmitti
Nathan K
NK
Yee
Neil
N
Moss
D000818:Animals; D001665:Binding Sites; D001682:Biological Availability; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D015195:Drug Design; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008958:Models, Molecular; D009536:Niacinamide / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013876:Thiophenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000737:chemistry*
D008070:Lipopolysaccharides; D047428:Protein Kinase Inhibitors; D013449:Sulfonamides; D013876:Thiophenes; D014409:Tumor Necrosis Factor-alpha; D009536:Niacinamide; D048051:p38 Mitogen-Activated Protein Kinases