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  • Design, synthesis, and in vivo SAR of a novel series of pyrazolines as potent selective androgen receptor modulators.

Design, synthesis, and in vivo SAR of a novel series of pyrazolines as potent selective androgen receptor modulators.

Journal of medicinal chemistry (2007-07-20)
Xuqing Zhang, Xiaojie Li, George F Allan, Tifanie Sbriscia, Olivia Linton, Scott G Lundeen, Zhihua Sui
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.

MATERIALS
Product Number
Brand
Product Description

Supelco
Discovery® Cyano Supelguard Cartridge, 5 μm particle size, L × I.D. 2 cm × 4 mm
Supelco
Discovery® Cyano HPLC Column, 5 μm particle size, L × I.D. 25 cm × 4 mm
Sigma-Aldrich
Testosterone propionate, solid
Supelco
Discovery® Cyano HPLC Column, 5 μm particle size, L × I.D. 15 cm × 4.6 mm
Supelco
Discovery® Cyano HPLC Column, 5 μm particle size, L × I.D. 25 cm × 4.6 mm