Optimization of Novel Antagonists to the Neurokinin-3 Receptor for the Treatment of Sex-Hormone Disorders (Part II)
2015; American Chemical Society; Volume: 6; Issue: 7 Linguagem: Inglês
10.1021/acsmedchemlett.5b00117
ISSN1948-5875
AutoresHamid R. Hoveyda, Graeme L. Fraser, Guillaume Dutheuil, Mohamed El Bousmaqui, Julien Korac, François Lenoir, Alexey Lapin, Sophie Noël,
Tópico(s)Receptor Mechanisms and Signaling
ResumoFurther 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.
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