Hoveyda, Hamid R. published the artcileDiscovery and Optimization of Novel Antagonists to the Human Neurokinin-3 Receptor for the Treatment of Sex-Hormone Disorders (Part I), HPLC of Formula: 1375066-73-1, the publication is Journal of Medicinal Chemistry (2015), 58(7), 3060-3082, database is CAplus and MEDLINE.
Neurokinin-3 receptor (NK3R) has recently emerged as important in modulating the tonic pulsatile gonadotropin-releasing hormone (GnRH) release. The authors therefore decided to explore NK3R antagonists as therapeutics for sex-hormone disorders that can potentially benefit from lowering GnRH pulsatility with consequent diminished levels of plasma LH and correspondingly attenuated levels of circulating androgens and estrogens. The discovery and lead optimization of a novel N-acyl-triazolopiperazine NK3R antagonist chemotype achieved through bioisosteric lead change from the high-throughput screening (HTS) hit is described. A concomitant improvement in the antagonist bioactivity and ligand lipophilic efficiency (LLE) parameter were the principal guidelines in the lead optimization efforts. Examples of advanced lead analogs to demonstrate the amenability of this chemotype to achieving a suitable pharmacokinetic (PK) profile are provided as well as pharmacokinetic-pharmacodynamic (PKPD) correlations to analyze the trends observed for LH inhibition in castrated rats and monkeys that served as preliminary in vivo efficacy models.
Journal of Medicinal Chemistry published new progress about 1375066-73-1. 1375066-73-1 belongs to thiazole, auxiliary class Thiadiazole,Hydrazine,Amine,Hydrazide,Amide, name is 3-Methyl-1,2,4-thiadiazole-5-carbohydrazide, and the molecular formula is C4H6N4OS, HPLC of Formula: 1375066-73-1.
Referemce:
https://pubchem.ncbi.nlm.nih.gov/compound/thiazole,
Thiazole | chemical compound | Britannica