Indanyl piperazines as melatonergic MT2 selective agents

Optimization of a benzyl piperazine pharmacophore produced N-acyl-4-indanyl-piperazines that bind with high affinity to melatonergic MT(2) receptors. (R)-4-(2,3-dihydro-6-methoxy-1H-inden-1-yl)-N-ethyl-1-piperazine-carboxamide fumarate (13) is a water soluble, selective MT(2) agonist, which produces...

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Bibliographic Details
Published inBioorganic & medicinal chemistry letters Vol. 13; no. 6; pp. 1199 - 1202
Main Authors MATTSON, Ronald J, CATT, John D, YOCCA, Frank D, KEAVY, Daniel, SLOAN, Charles P, EPPERSON, James, QI GAO, HODGES, Donald B, IBEN, Lawrence, MAHLE, Cathy D, RYAN, Elaine
Format Journal Article
LanguageEnglish
Published Oxford Elsevier 24.03.2003
Subjects
3T3 Cells
Adenylyl Cyclases - metabolism
Animals
Biological and medical sciences
Circadian Rhythm - drug effects
Humans
In Vitro Techniques
Indicators and Reagents
Male
Medical sciences
Mice
Muscle Contraction - drug effects
Muscle, Smooth, Vascular - drug effects
Neuropharmacology
Neurotransmitters. Neurotransmission. Receptors
Peptidergic system (neuropeptide, opioid peptide, opiates...). Adenosinergic and purinergic systems
Pharmacology. Drug treatments
Piperazines - chemical synthesis
Piperazines - metabolism
Piperazines - pharmacology
Rats
Rats, Long-Evans
Receptors, Cell Surface - agonists
Receptors, Cell Surface - metabolism
Receptors, Cytoplasmic and Nuclear - agonists
Receptors, Cytoplasmic and Nuclear - metabolism
Receptors, Melatonin
Agonist
Indan derivatives
Rat
Nitrogen heterocycle
Rodentia
Selectivity
Circadian rhythm
In vitro
Water soluble compound
In vivo
Vertebrata
Mammalia
Structure activity relation
Animal
Bicyclic compound
Affinity
Aromatic compound
MT2 melatonin receptor
Chemical synthesis
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Summary:Optimization of a benzyl piperazine pharmacophore produced N-acyl-4-indanyl-piperazines that bind with high affinity to melatonergic MT(2) receptors. (R)-4-(2,3-dihydro-6-methoxy-1H-inden-1-yl)-N-ethyl-1-piperazine-carboxamide fumarate (13) is a water soluble, selective MT(2) agonist, which produces advances in circadian phase in rats at doses of 1-56 mg/kg that are no different from those of melatonin at 1 mg/kg. Unlike melatonin, 13 produced only weak contractile effects in rat tail artery.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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ISSN:0960-894X
1464-3405
DOI:10.1016/S0960-894X(03)00090-8