Identification, synthesis, and biological evaluation of novel pyrazoles as low molecular weight luteinizing hormone receptor agonists

The synthesis and structure–activity relationship of pyrazole derivatives are described as novel low molecular weight LH-receptor agonists. In the course of a high throughput screening, a series of pyrazole compounds were identified with luteinizing hormone receptor (LH-R) agonist activity. A focused pyrazole library was produced by solid-phase synthesis and key pyrazole regioisomers were obtained selectively in solution. Evaluation of those compounds in a cAMP assay in CHO cells transfected with h-LH receptor allowed us to propose a structure–activity relationship model for this series and led to the identification of the first low molecular weight molecule with in vitro activity in a Leydig cells assay (ED 50 = 1.31 μM) and in vivo in a model of testosterone induction in rats (significant effect at 32 mpk ip).