title: Optimization of Novel Antagonists to the Neurokinin-3 Receptor for the Treatment of Sex-Hormone Disorders (Part II).
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.
authors.affiliation: Euroscreen SA , 47 rue Adrienne Bolland, 6041 Gosselies, Belgium.
authors.forename: Hamid R
authors.initials: HR
authors.lastname: Hoveyda
authors.affiliation: Euroscreen SA , 47 rue Adrienne Bolland, 6041 Gosselies, Belgium.
authors.forename: Graeme L
authors.initials: GL
authors.lastname: Fraser
authors.affiliation: Euroscreen SA , 47 rue Adrienne Bolland, 6041 Gosselies, Belgium.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Dutheuil
authors.affiliation: Euroscreen SA , 47 rue Adrienne Bolland, 6041 Gosselies, Belgium.
authors.forename: Mohamed
authors.initials: M
authors.lastname: El Bousmaqui
authors.affiliation: Euroscreen SA , 47 rue Adrienne Bolland, 6041 Gosselies, Belgium.
authors.forename: Julien
authors.initials: J
authors.lastname: Korac
authors.affiliation: Euroscreen SA , 47 rue Adrienne Bolland, 6041 Gosselies, Belgium.
authors.forename: François
authors.initials: F
authors.lastname: Lenoir
authors.affiliation: Euroscreen SA , 47 rue Adrienne Bolland, 6041 Gosselies, Belgium.
authors.forename: Alexey
authors.initials: A
authors.lastname: Lapin
authors.affiliation: Euroscreen SA , 47 rue Adrienne Bolland, 6041 Gosselies, Belgium.
authors.forename: Sophie
authors.initials: S
authors.lastname: Noël
keywords: FSH; GnRH; LH; NK3 antagonist; neurokinin B; triazolopiperazine