Characterization of a new class of selective nonsteroidal progesterone receptor agonists

Dynamics of progestogenic activity in serum following administration of Ligusticum chuanxiong

“…The dynamic ranges of the assay with regards to progestogenic activity (8.2-fold increase in geometric mean AUC) were comparable with current animal physiological assays (Dong et al, 2004;Schubert et al, 2005;Kurata et al, 2005). Using this metric, the effect of a subcutaneous injection of L. chuanxiong was significant and resulted in a 4.5-fold increase in geometric mean AUC (Table 1).…”

“…Physiological responses in whole animal assays can capture progestogenic activity but take days and weeks and are therefore not suitable for measuring the short term effects that are required to establish basic PK/PD parameters for drug formulation. Moreover such animal experiments depend on indirect and cumbersome metrics such as anti-estrogenic effects in the uteri of estrogen-primed ovariectomized rats, luteinizing hormone releasing assay in young ovariectomized rats (Dong et al, 2004), ClaubergMcPhail test of endometrial transformation in rabbits (Kurata et al, 2005), labor and parturition in guinea pigs (Schubert et al, 2005). We elected to use reporter-gene bioassays as they are rapidly performed, and can measure activity of samples at precise time points.…”

Applicability Aspects of Transition Metal‐Catalyzed Aromatic Amination Protocols in Medicinal Chemistry

“…As with S N Ar amination reactions, [43] Pd-catalyzed ones can also be performed as parallel syntheses using standard reactor blocks which enable a reaction performance in an inert atmosphere.…”

Benzimidazole: a medicinally important heterocyclic moiety

“…Synthetic steroidal progestins are widely used as therapeutic agents in the control of fertility, combination hormonal replacement therapy and variety of endocrinologic diseases. Dong et al in their search of a selective nonsteroidal progesterone receptor agonist identified that compound 52, 1-cyclopentyl-6-imidazol-1-yl-1H-benzoimidazole-2-thiol, binds to human progesterone receptor with high affinity (K i = 28 nM) (Dong et al, 2004).…”