Synthesis, Structure−Activity Relationships, and Characterization of Novel Nonsteroidal and Selective Androgen Receptor Modulators
Nathalie Schlienger
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
10.1021/jm901149c.s001
https://acs.figshare.com/articles/journal_contribution/Synthesis_Structure_Activity_Relationships_and_Characterization_of_Novel_Nonsteroidal_and_Selective_Androgen_Receptor_Modulators/2810146
Herein we describe the discovery of ACP-105 (<b>1</b>), a novel and potent nonsteroidal selective androgen receptor modulator (SARM) with partial agonist activity relative to the natural androgen testosterone. Compound <b>1</b> was developed from a series of compounds found in a HTS screen using the receptor selection and amplification technology (R-SAT). In vivo, <b>1</b> improved anabolic parameters in a 2-week chronic study in castrated male rats. In addition to compound <b>1</b>, a number of potent antiandrogens were discovered from the same series of compounds whereof one compound, <b>13</b>, had antagonist activity at the AR T877A mutant involved in prostate cancer.
2009-11-26 00:00:00
amplification technology
series
HTS screen
Novel Nonsteroidal
Selective Androgen Receptor ModulatorsHerein
agonist activity
AR T 877A
receptor selection
prostate cancer
anabolic parameters
antagonist activity
androgen testosterone
compound
SARM
Compound 1
androgen receptor modulator
ACP