Identification of a novel series of tetrahydrodibenzazocines as inhibitors of 17beta-hydroxysteroid dehydrogenase type 3

Brian E Fink; Ashvinikumar V Gavai; John S Tokarski; Bindu Goyal; Raj Misra; Hai-Yun Xiao; S David Kimball; Wen-Ching Han; Derek Norris; Thomas E Spires; Dan You; Marco M Gottardis; Matthew V Lorenzi; Gregory D Vite

doi:10.1016/j.bmcl.2005.12.039

Identification of a novel series of tetrahydrodibenzazocines as inhibitors of 17beta-hydroxysteroid dehydrogenase type 3

Bioorg Med Chem Lett. 2006 Mar 15;16(6):1532-6. doi: 10.1016/j.bmcl.2005.12.039. Epub 2006 Jan 4.

Authors

Brian E Fink¹, Ashvinikumar V Gavai, John S Tokarski, Bindu Goyal, Raj Misra, Hai-Yun Xiao, S David Kimball, Wen-Ching Han, Derek Norris, Thomas E Spires, Dan You, Marco M Gottardis, Matthew V Lorenzi, Gregory D Vite

Affiliation

¹ Department of Oncology Chemistry, Bristol-Myers Squibb Pharmaceutical Research Institute, PO Box 4000, Princeton, NJ 08543-4000, USA. brian.fink@bms.com

PMID: 16386902
DOI: 10.1016/j.bmcl.2005.12.039

Abstract

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.

MeSH terms

17-Hydroxysteroid Dehydrogenases / antagonists & inhibitors*
17-Hydroxysteroid Dehydrogenases / metabolism
Alkaline Phosphatase / drug effects
Alkaline Phosphatase / metabolism
Androstenedione / metabolism
Azocines* / chemical synthesis
Azocines* / chemistry
Azocines* / pharmacology
Enzyme Inhibitors* / chemical synthesis
Enzyme Inhibitors* / chemistry
Enzyme Inhibitors* / pharmacology
Humans
Models, Molecular
Molecular Structure
Structure-Activity Relationship
Testosterone / biosynthesis

Substances

Azocines
Enzyme Inhibitors
Testosterone
Androstenedione
17-Hydroxysteroid Dehydrogenases
17beta-hydroxysteroid dehydrogenase type 3
Alkaline Phosphatase