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...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2011-03, Vol.21 (5), p.1498-1501
Main Authors: 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: Article
Language:English
Subjects:
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
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Summary: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