Novel series of potent, nonsteroidal, selective androgen receptor modulators based on 7H-[1,4]oxazino[3,2-g]quinolin-7-ones
| Autor: | Neelakhanda S. Mani, Dale E. Mais, Francisco J. López, Kristen L. Arienti, Lin Zhi, Yun Oliver Long, William T. Schrader, Todd K. Jones, James P. Edwards, and Andrés Negro-Vilar, Thomas R. Caferro, Keith B. Marschke, Robert I. Higuchi |
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| Rok vydání: | 2007 |
| Předmět: |
Agonist
Male Transcriptional Activation medicine.medical_specialty medicine.drug_class medicine.medical_treatment Pharmacology Quinolones urologic and male genital diseases Binding Competitive Anabolic Agents Rats Sprague-Dawley Radioligand Assay Structure-Activity Relationship Internal medicine Cell Line Tumor Drug Discovery Oxazines medicine Structure–activity relationship Animals Humans Hormone replacement therapy Receptor Muscle Skeletal Chemistry Prostate Stereoisomerism Organ Size Rats Androgen receptor Endocrinology Selective androgen receptor modulator Receptors Androgen Androgens Molecular Medicine Androgen replacement therapy |
| Zdroj: | Journal of medicinal chemistry. 50(10) |
| ISSN: | 0022-2623 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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