Novel series of potent, nonsteroidal, selective androgen receptor modulators based on 7H-[1,4]oxazino[3,2-g]quinolin-7-ones.
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Higuchi RI, Arienti KL, Lopez FJ, Mani NS, Mais DE, Caferro TR, Long YO, Jones TK, Edwards JP, Zhi L, Schrader WT, Negro-Vilar A, Marschke KB
Novel series of potent, nonsteroidal, selective androgen receptor modulators based on 7H-[1,4]oxazino[3,2-g]quinolin-7-ones.
J Med Chem. 2007 May 17;50(10):2486-96. Epub 2007 Apr 17.
- PubMed ID
- 17439112 [ View in PubMed]
- Abstract
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.
DrugBank Data that Cites this Article
- Binding Properties
Drug Target Property Measurement pH Temperature (°C) Fluoxymesterone Androgen receptor Ki (nM) 5.7 7.4 37 Details Fluoxymesterone Androgen receptor EC 50 (nM) 0.3 7.4 37 Details Stanolone Androgen receptor Ki (nM) 0.3 7.4 37 Details Stanolone Androgen receptor EC 50 (nM) 5.7 7.4 37 Details