Design, Synthesis, and in Vivo Sar of a Novel Series of Pyrazolines As Potent Selective Androgen Receptor Modulators.
From: Drug Discovery, Johnson & Johnson Pharmaceutical Research and Development, LLC, 665 Stockton Drive, Exton, PA 19341, USA. xzhang@prdus.jnj.com
Journal of medicinal chemistry
- Publish Date: Aug 2007
- ISSN: 0022-2623
- Volume: 50
- Issue: 16
- Pages: 3857-69
- Medium: Print
- Language: English
- Citation (JAMA): Zhang Xuqing, Li Xiaojie, Allan George F, et al. Design, Synthesis, and in Vivo Sar of a Novel Series of Pyrazolines As Potent Selective Androgen Receptor Modulators.. J. Med. Chem. Aug 2007;50:3857-69
Abstract
A novel series of pyrazolines 2 have been designed, synthesized, and evaluated by in vivo screening as tissue-selective androgen receptor modulators (SARMs). Structure-activity relationships (SAR) were investigated at the R1 to R6 positions as well as the core pyrazoline ring and the anilide linker. Overall, strong electron-withdrawing groups at the R1 and R2 positions and a small group at the R5 and R6 position are optimal for AR agonist activity. The (S)-isomer of 7c exhibits more potent AR agonist activity than the corresponding (R)-isomer. (S)-7c exhibited an overall partial androgenic effect but full anabolic effect via oral administration in castrated rats. It demonstrated a noticeable antiandrogenic effect on prostate in intact rats with endogenous testosterone. Thus, (S)-7c is a tissue-selective nonsteroidal androgen receptor modulator with agonist activity on muscle and mixed agonist and antagonist activity on prostate.
Mesh Headings (Keywords): Anabolic Agents, Anilides, Animals, Crystallography, X-Ray, Drug Design, Male, Molecular Structure, Muscle, Skeletal, Orchiectomy, Organ Size, Pelvic Floor, Prostate, Pyrazoles, Rats, Rats, Sprague-Dawley, Receptors, Androgen, Stereoisomerism, Structure-Activity Relationship, Testosterone
Check for Full Text / PubMed Unique Identifier (PMID): 17636947
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