Novel small molecule neurotensin antagonists: 3-(1,5-diaryl-1,5-dioxopentan-3-yl)benzoic acids

Novel small molecule neurotensin antagonists: 3-(1,5-diaryl-1,5-dioxopentan-3-yl)benzoic acids

Screening in a neurotensin (NT) receptor binding assay resulted in the discovery of compound 1 with NT receptor binding affinity of 450 nM. SAR studies that varied substituents on each aromatic ring and the linking 1,5-pentanedione chain lead to compound 39 with 42 nM affinity. The more potent compo...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters Vol. 7; no. 5; pp. 561 - 566
Main Authors: Johnson, S.J., Akunne, H.C., Heffner, T.G., Kesten, S.R., Pugsley, T.A., Wise, L.D., Wustrow, D.J.
Format: Journal Article
Language:English
Published: Oxford Elsevier Ltd 04-03-1997
Elsevier
Subjects:
Biological and medical sciences
Medical sciences
Neuropharmacology
Neurotransmitters. Neurotransmission. Receptors
Peptidergic system (neuropeptide, opioid peptide, opiates...). Adenosinergic and purinergic systems
Pharmacology. Drug treatments
Rodentia
Central nervous system
Diketone
Neurotensin
In vitro
Vertebrata
Mammalia
Structure activity relation
Mouse
Carboxylic acid
Animal
Peptidergic receptor
Benzenic compound
Antagonist
Chemical synthesis
Brain (vertebrata)
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Summary:Screening in a neurotensin (NT) receptor binding assay resulted in the discovery of compound 1 with NT receptor binding affinity of 450 nM. SAR studies that varied substituents on each aromatic ring and the linking 1,5-pentanedione chain lead to compound 39 with 42 nM affinity. The more potent compounds were shown to be NT antagonists by their ability to inhibit NT induced calcium mobilization in HT29 cells. Screening in a neurotensin (NT) receptor binding assay resulted in the discovery of compound 1 with NT receptor binding affinity of 450 nM. SAR studies that varied substituents on each aromatic ring and the linking 1,5-pentanedione chain lead to compound 39 with 42 nM affinity. The more potent compounds were shown to be NT antagonists by their ability to inhibit NT induced calcium mobilization in HT29 cells.
ISSN:0960-894X
1464-3405
DOI:10.1016/S0960-894X(97)00067-X