Synthesis and Biological Evaluation of Second-Generation Tropanol-Based Androgen Receptor Modulators
Journal article, 2015
To circumvent antiandrogen resistance in prostate cancer, antiandrogens effective for both the androgen receptor (AR) and AR mutants are required. The AR antagonists in this study originate from previous findings, which showed that subtle differences in substitution pattern lead to a conformational change that alters the ligand activity, rendering an agonist to an antagonist. We have identified small yet potent tropanol-based ligands possessing significant antiandrogenic activity with both wild-type AR and the two most common AR ligand binding domain (LBD) mutants.
DESIGN
RESISTANT PROSTATE-CANCER
BETA-AGONIST
POTENT
SERIES
Chemistry
ANTIANDROGEN RESISTANCE
IDENTIFICATION
DISCOVERY
Medicinal
ANTAGONISTS
ANTI-ANDROGENS
Author
Henrik Sundén
University of Gothenburg
Mareike C. Holland
University of Gothenburg
P. K. Poutiainen
T. Jaaskelainen
J. T. Pulkkinen
J. J. Palvimo
Roger Olsson
University of Gothenburg
Journal of Medicinal Chemistry
0022-2623 (ISSN) 1520-4804 (eISSN)
Vol. 58 3 1569-1574Subject Categories
Chemical Sciences
DOI
10.1021/jm501995n