Optimization of Novel Antagonists to the Neurokinin-3 Receptor for the Treatment of Sex-Hormone Disorders (Part II)

[Image: see text] Further lead optimization on N-acyl-triazolopiperazine antagonists to the neurokinin-3 receptor (NK(3)R) 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 castra...

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Autores principales: Hoveyda, Hamid R., Fraser, Graeme L., Dutheuil, Guillaume, El Bousmaqui, Mohamed, Korac, Julien, Lenoir, François, Lapin, Alexey, Noël, Sophie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2015
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4499830/
https://www.ncbi.nlm.nih.gov/pubmed/26191358
http://dx.doi.org/10.1021/acsmedchemlett.5b00117
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author Hoveyda, Hamid R.
Fraser, Graeme L.
Dutheuil, Guillaume
El Bousmaqui, Mohamed
Korac, Julien
Lenoir, François
Lapin, Alexey
Noël, Sophie
author_facet Hoveyda, Hamid R.
Fraser, Graeme L.
Dutheuil, Guillaume
El Bousmaqui, Mohamed
Korac, Julien
Lenoir, François
Lapin, Alexey
Noël, Sophie
author_sort Hoveyda, Hamid R.
collection PubMed
description [Image: see text] Further lead optimization on N-acyl-triazolopiperazine antagonists to the neurokinin-3 receptor (NK(3)R) 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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spelling pubmed-44998302016-07-09 Optimization of Novel Antagonists to the Neurokinin-3 Receptor for the Treatment of Sex-Hormone Disorders (Part II) Hoveyda, Hamid R. Fraser, Graeme L. Dutheuil, Guillaume El Bousmaqui, Mohamed Korac, Julien Lenoir, François Lapin, Alexey Noël, Sophie ACS Med Chem Lett [Image: see text] Further lead optimization on N-acyl-triazolopiperazine antagonists to the neurokinin-3 receptor (NK(3)R) 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. American Chemical Society 2015-05-19 /pmc/articles/PMC4499830/ /pubmed/26191358 http://dx.doi.org/10.1021/acsmedchemlett.5b00117 Text en Copyright © 2015 American Chemical Society This is an open access article published under an ACS AuthorChoice License (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html) , which permits copying and redistribution of the article or any adaptations for non-commercial purposes.
spellingShingle Hoveyda, Hamid R.
Fraser, Graeme L.
Dutheuil, Guillaume
El Bousmaqui, Mohamed
Korac, Julien
Lenoir, François
Lapin, Alexey
Noël, Sophie
Optimization of Novel Antagonists to the Neurokinin-3 Receptor for the Treatment of Sex-Hormone Disorders (Part II)
title Optimization of Novel Antagonists to the Neurokinin-3 Receptor for the Treatment of Sex-Hormone Disorders (Part II)
title_full Optimization of Novel Antagonists to the Neurokinin-3 Receptor for the Treatment of Sex-Hormone Disorders (Part II)
title_fullStr Optimization of Novel Antagonists to the Neurokinin-3 Receptor for the Treatment of Sex-Hormone Disorders (Part II)
title_full_unstemmed Optimization of Novel Antagonists to the Neurokinin-3 Receptor for the Treatment of Sex-Hormone Disorders (Part II)
title_short Optimization of Novel Antagonists to the Neurokinin-3 Receptor for the Treatment of Sex-Hormone Disorders (Part II)
title_sort optimization of novel antagonists to the neurokinin-3 receptor for the treatment of sex-hormone disorders (part ii)
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4499830/
https://www.ncbi.nlm.nih.gov/pubmed/26191358
http://dx.doi.org/10.1021/acsmedchemlett.5b00117
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