Details

Autor(en) / Beteiligte

• Higuchi, Robert I
• Arienti, Kristen L
• López, Francisco J
• Mani, Neelakhanda S
• Mais, Dale E
• Caferro, Thomas R
• Long, Yun Oliver
• Jones, Todd K
• Edwards, James P
• Zhi, Lin
• Schrader, William T
• Negro-Vilar, Andrés
• Marschke, Keith B

Titel

Novel Series of Potent, Nonsteroidal, Selective Androgen Receptor Modulators Based on 7H-[1,4]Oxazino[3,2-g]quinolin-7-ones

Ist Teil von

• Journal of medicinal chemistry, 2007-05, Vol.50 (10), p.2486-2496

Ort / Verlag

Washington, DC: American Chemical Society

Erscheinungsjahr

2007

Quelle

MEDLINE

Beschreibungen/Notizen

• Recent interest in orally available androgens has fueled the search for new androgens for use in hormone replacement therapy and as anabolic agents. In pursuit of this, we have discovered a series of novel androgen receptor modulators derived from 7H-[1,4]oxazino[3,2-g]quinolin-7-ones. These compounds were synthesized and evaluated in competitive binding assays and an androgen receptor transcriptional activation assay. A number of compounds from the series demonstrated single-digit nanomolar agonist activity in vitro. In addition, lead compound ( R )-16e was orally active in established rodent models that measure androgenic and anabolic properties of these agents. In this assay, ( R )-16e demonstrated full efficacy in muscle and only partially stimulated the prostate at 100 mg/kg. These data suggest that these compounds may be utilized as selective androgen receptor modulators or SARMs. This series represents a novel class of compounds for use in androgen replacement therapy.