Indanyl piperazines as melatonergic MT2 selective agents.
Mattson RJ,
Catt JD,
Keavy D,
Sloan CP,
Epperson J,
Gao Q,
Hodges DB,
Iben L,
Mahle CD,
Ryan E,
Yocca FD.
Bristol-Myers Squibb Pharmaceutical Research Institute, Wallingford, CT 06492-7660, USA. mattsonr@bms.com
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.
PMID: 12643943 [PubMed - indexed for MEDLINE]