Identification of a novel series of tetrahydrodibenzazocines as inhibitors of 17beta-hydroxysteroid dehydrogenase type 3.
A novel series of 17beta-hydroxysteroid dehydrogenase type 3 (17beta-HSD3) inhibitors has been identified. These inhibitors, based on a dibenzazocine core, exhibited picomolar to low nanomolar inhibition of 17beta-HSD3 in cell-free enzymatic as well as in cell-based transcriptional reporter assays.
Fink
Brian E
BE
Department of Oncology Chemistry, Bristol-Myers Squibb Pharmaceutical Research Institute, PO Box 4000, Princeton, NJ 08543-4000, USA. brian.fink@bms.com
Gavai
Ashvinikumar V
AV
Tokarski
John S
JS
Goyal
Bindu
B
Misra
Raj
R
Xiao
Hai-Yun
HY
Kimball
S David
SD
Han
Wen-Ching
WC
Norris
Derek
D
Spires
Thomas E
TE
You
Dan
D
Gottardis
Marco M
MM
Lorenzi
Matthew V
MV
Vite
Gregory D
GD
D015067:17-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000469:Alkaline Phosphatase / Q000187:drug effects / Q000378:metabolism; D000735:Androstenedione / Q000378:metabolism; D001392:Azocines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013739:Testosterone / Q000096:biosynthesis
D001392:Azocines; D004791:Enzyme Inhibitors; D013739:Testosterone; D000735:Androstenedione; D015067:17-Hydroxysteroid Dehydrogenases; C476565:17beta-hydroxysteroid dehydrogenase type 3; D000469:Alkaline Phosphatase