Synthesis, structure-activity relationships, and characterization of novel nonsteroidal and selective androgen receptor modulators

  • J Med Chem. 2009 Nov 26;52(22):7186-91. doi: 10.1021/jm901149c.
Nathalie Schlienger  1 ,  Birgitte W Lund ,  Jan Pawlas ,  Fabrizio Badalassi ,  Fabio Bertozzi ,  Rasmus Lewinsky ,  Alma Fejzic ,  Mikkel B Thygesen ,  Ali Tabatabaei ,  Stefania Risso Bradley ,  Luis R Gardell ,  Fabrice Piu ,  Roger Olsson
Affiliations
  • 1. ACADIA Pharmaceuticals AB, Medeon Science Park, S-205 12 Malmo, Sweden.
PMID: 19856921 DOI: 10.1021/jm901149c
Abstract

Herein we describe the discovery of ACP-105 (1), a novel and potent nonsteroidal selective Androgen Receptor Modulator (SARM) with partial agonist activity relative to the natural androgen testosterone. Compound 1 was developed from a series of compounds found in a HTS screen using the receptor selection and amplification technology (R-SAT). In vivo, 1 improved anabolic parameters in a 2-week chronic study in castrated male rats. In addition to compound 1, a number of potent antiandrogens were discovered from the same series of compounds whereof one compound, 13, had antagonist activity at the AR T877A mutant involved in prostate Cancer.

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