Identification of a new series of non-peptidic NK₃ receptor antagonists

The identification and structure–activity relationships of 2-aminomethyl-1-aryl cyclopropane carboxamides as novel NK₃ receptor antagonists are reported. The compound series was optimized to give analogues with low nanomolar binding to the NK₃ receptor and brain exposure, leading to activity in vivo...

Ausführliche Beschreibung

Gespeichert in:

Bibliographische Detailangaben
Veröffentlicht in:	Bioorganic & medicinal chemistry letters 2011-03, Vol.21 (5), p.1498-1501
Hauptverfasser:	Juhl, Karsten, Hansen, Tore, Kehler, Jan, Khanzhin, Nikolay A, Nørgaard, Morten B, Ruhland, Thomas, Larsen, Dorrit B, Jensen, Klaus G, Steiniger-Brach, Björn, Nielsen, Søren M, Simonsen, Klaus B
Format:	Artikel
Sprache:	eng
Schlagworte:	Amides - chemical synthesis Amides - chemistry Amides - pharmacology Animals antagonists Biological and medical sciences brain Carboxylic Acids - chemical synthesis Carboxylic Acids - chemistry Carboxylic Acids - pharmacology Cyclopropanes - chemical synthesis Cyclopropanes - chemistry Cyclopropanes - pharmacology Disease Models, Animal Gerbillinae gerbils Medical sciences Molecular Structure Neuropharmacology Neurotransmitters. Neurotransmission. Receptors Peptidergic system (neuropeptide, opioid peptide, opiates...). Adenosinergic and purinergic systems Peptides - chemical synthesis Peptides - chemistry Peptides - pharmacology Pharmacology. Drug treatments Psycholeptics: tranquillizer, neuroleptic Psychology. Psychoanalysis. Psychiatry Psychopharmacology Receptors, Neurokinin-3 - antagonists & inhibitors Structure-Activity Relationship structure-activity relationships
Online-Zugang:	Volltext
Tags:	Tag hinzufügen Keine Tags, Fügen Sie den ersten Tag hinzu!

Beschreibung
Zusammenfassung:	The identification and structure–activity relationships of 2-aminomethyl-1-aryl cyclopropane carboxamides as novel NK₃ receptor antagonists are reported. The compound series was optimized to give analogues with low nanomolar binding to the NK₃ receptor and brain exposure, leading to activity in vivo in the senktide-induced hypoactivity model in gerbils.
ISSN:	0960-894X 1464-3405
DOI:	10.1016/j.bmcl.2010.12.135