Abstract
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.
MeSH terms
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3T3 Cells
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Adenylyl Cyclases / metabolism
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Animals
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Circadian Rhythm / drug effects
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Humans
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In Vitro Techniques
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Indicators and Reagents
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Male
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Mice
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Muscle Contraction / drug effects
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Muscle, Smooth, Vascular / drug effects
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Piperazines / chemical synthesis*
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Piperazines / metabolism
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Piperazines / pharmacology*
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Rats
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Rats, Long-Evans
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Receptors, Cell Surface / agonists*
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Receptors, Cell Surface / metabolism
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Receptors, Cytoplasmic and Nuclear / agonists*
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Receptors, Cytoplasmic and Nuclear / metabolism
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Receptors, Melatonin
Substances
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Indicators and Reagents
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Piperazines
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Receptors, Cell Surface
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Receptors, Cytoplasmic and Nuclear
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Receptors, Melatonin
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Adenylyl Cyclases