Discovery of novel dihydro-9,10-ethano-anthracene carboxamides as glucocorticoid receptor modulators.
A series of dihydro-9,10-ethano-anthracene-11-carboxamides as novel glucocorticoid receptor modulators is reported. SAR exploration identified compounds from this series displaying a promising dissociation profile in discriminating between transrepression and transactivation activities. 17a is a partial agonist of GR-mediated transactivation which elicits potent and efficacious transrepression in reporter gene assays. A hypothetical binding mode is provided which accounts for the induction of functional activity by a bridgehead methyl group.
Yang
Bingwei V
BV
Department of Discovery Chemistry, Bristol-Myers Squibb, Research and Development, Princeton, NJ 08543, USA. bingwei.yang@bms.com
Vaccaro
Wayne
W
Doweyko
Arthur M
AM
Doweyko
Lidia M
LM
Huynh
Tram
T
Tortolani
David
D
Nadler
Steven G
SG
McKay
Lorraine
L
Somerville
John
J
Holloway
Deborah A
DA
Habte
Sium
S
Weinstein
David S
DS
Barrish
Joel C
JC