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 1569-1574

Subject Categories

Chemical Sciences

DOI

10.1021/jm501995n