Optimization of Novel Antagonists to the Neurokinin-3 Receptor for the Treatment of Sex-Hormone Disorders (Part II).
Basic Information
ID: ALA3608214
Journal: ACS Med Chem Lett
Title: Optimization of Novel Antagonists to the Neurokinin-3 Receptor for the Treatment of Sex-Hormone Disorders (Part II).
Authors: Hoveyda HR, Fraser GL, Dutheuil G, El Bousmaqui M, Korac J, Lenoir F, Lapin A, Noël S.
Abstract: Further lead optimization on N-acyl-triazolopiperazine antagonists to the neurokinin-3 receptor (NK3R) based on the concurrent improvement in bioactivity and ligand lipophilic efficiency (LLE) is reported. Overall, compound 3 (LLE > 6) emerged as the most efficacious in castrated rat and monkey to lower plasma LH, and it displayed the best off-target safety profile that led to its clinical candidate nomination for the treatment of sex-hormone disorders.
CiteXplore: 26191358
DOI: 10.1021/acsmedchemlett.5b00117
Patent ID: ┄