Conformation by NMR of two tetralin-based receptor ligands.
The conformation in solution of 1-phenyl-3-propionamido-1,2,3,4-tetrahydronaphthalene and 1-phenyl-3-(N,N-dimethylamino)-1,2,3,4-tetrahydronaphthalene has been determined by a combination of nuclear magnetic resonance measurements and molecular mechanics calculations. The results indicate that in the cis isomers the cyclohexene ring is in a locked conformation and the trans isomers correspond to a mixture of the two inverted half chairs. Moreover, the data allowed the identification of the two purposely-synthesized geometrical isomers of 1-phenyl-3-propionamidotetralin. Binding studies on melatonin receptor subtypes showed that the (+/-)-cis-1-phenyl-3-propionamido-1,2,3,4-tetrahydronaphthalene has higher affinity and selectivity ratio toward the MT(2) subtype than the (+/-)-trans-isomer.
Gatti
Giuseppe
G
Istituto di Chimica Farmaceutica, Università degli Studi di Urbino, Piazza Rinascimento 6, I-61029 Urbino, Italy. g.gatti@uniurb.it
Piersanti
Giovanni
G
Spadoni
Gilberto
G
D001665:Binding Sites / Q000187:drug effects / Q000502:physiology; D003510:Cyclohexanes / Q000138:chemical synthesis; D053138:Cyclohexenes; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008668:Metallothionein / Q000187:drug effects; D044094:Receptors, Melatonin / Q000737:chemistry*; D013764:Tetrahydronaphthalenes / Q000378:metabolism*
D003510:Cyclohexanes; D053138:Cyclohexenes; D044094:Receptors, Melatonin; D013764:Tetrahydronaphthalenes; C052568:cyclohexene; D008668:Metallothionein; C095210:tetralin