80270-68-4Relevant academic research and scientific papers
Synthesis of 2-amido-2,3-dihydro-1H-phenalene derivatives as new conformationally restricted ligands for melatonin receptors
Mathé-Allainmat, Monique,Gaudy, Florence,Sicsic, Sames,Dangy-Caye, Anne-Laure,Shen, Shuren,Brémont, Béatrice,Benatalah, Zohra,Langlois, Michel,Renard, Pierre,Delagrange, Philippe
, p. 3089 - 3095 (2007/10/03)
Tetrahydroanthracene, tetrahydrophenanthrene, and tetrahydrophenalene moieties were used to design novel constrained melatoninergic agents. Compounds 1 and 2 were synthesized from the cyclization of the aryl succinic acids 6a,b followed by catalytic reduction, Curtius degradation to the amino derivatives, and acetylation. The phenalene derivatives 3 were prepared by cyclization of the aza lactones of the corresponding α-N-acetyl amino acids. The ketone derivatives were reduced directly by catalytic hydrogenation to produce the compounds 3. The different compounds were evaluated in vitro in binding assays using 2-[125I]iodomelatonin and chicken brain membranes. Melatonin and 2-acetamido-8-methoxytetralin were used as the reference compounds. The results showed the superiority of the dihydrophenalene framework 3 over those of tetrahydroanthracene and tetrahydrophenanthrene. 3a had relatively good affinity for melatonin receptors (K(i) = 28.7 nM). Introduction of an additional methoxy group gave a derivative (3c) with nanomolar affinity (K(i) = 0.7 nM), confirming the existence of a secondary binding site in the receptor which has been described previously. An increase in the affinity was also observed with the propionamido derivative 3e (K(i) = 6.0 nM). The potential agonist properties of the compound 3e were evaluated on the dermal melanocytes of Xenopus laevis tadpoles. At the concentration of 2.3 nM (5 x K(i)), melatonin gave a melanophore index value of 1. Similarly to melatonin, 3e was shown to be a potent agonist of the melanosome aggregation.
2-Amido-8-methoxytetralins: A Series of Nonindolic Melatonin-like Agents
Copinga, Swier,Tepper, Pieter G.,Grol, Cor J.,Horn, Alan S.,Dubocovich, Margarita L.
, p. 2891 - 2898 (2007/10/02)
A series of unsubstituted and methoxy-substituted 2-amidotetralins (4a-q) was prepared and evaluated for their ability to complete for 2-iodomelatonin binding to chicken retinal membranes and for their potency to inhibit the calcium-dependent release of dopamine from rabbit retina.The lead compound, 2-acetamido-8-methoxytetralin (4j), showed a moderate affinity (Ki = 46 nM) and potency (IC50 = 1.4 nM) at the melatonin receptor.The structural requirements necessary for optimal agonistic activity at the melatonin receptor are as follows.First, the amido group, which should have a small, nonbranched alkyl group, is essential for affinity, and second, the methoxy substituent at the 8-position of the 2-amidotetralin ring is essential for optimal agonistic activity at the melatonin receptor.We concluded that this series of unsubstituted and methoxy-substituted 2-amidotetralins constitutes a class of nonindolic melatonin-like agents that can be used as pharmacological tools to further characterize melatonin receptors and to elucidate the mode of action of melatonin.
SUBSTITUTED 2-AMIDOTETRALINS AS MELATONIN AGONISTS AND ANTAGONISTS
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, (2008/06/13)
The present invention relates generally to compounds having melatonin receptor activities and in particular to substituted 2-amidotetralin derivatives; to pharmaceutical preparations comprising such compounds; and to methods for using these compounds as t
SUBSTITUTED 2-AMIDOTETRALINS AS MELATONIN AGONISTS AND ANTAGONISTS
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, (2008/06/13)
The present invention relates generally to compounds having melatonin receptor activities and in particular to substituted 2-amidotetralin derivatives; to pharmaceutical preparations comprising such compounds; and to methods for using these compounds as t
2-Aminotetralin compounds, pharmaceutical compositions and method of producing central alpha1 agonist activity
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, (2008/06/13)
2-Aminotetralin compounds having 5- and 8- substituents are centrally acting alpha1 agonists.
α-Adrenergic Agents. 2. Synthesis and α1-Agonist Activity of 2-Aminotetralins
DeMarinis, R. M.,Shah, D. H.,Hall, R. F.,Hieble, J. P.,Pendleton, R. G.
, p. 136 - 141 (2007/10/02)
Substituted 2-aminotetralins are potent, selective, direct-acting agonists as postjunctional α1 receptors.Within this series, substituent alterations on the ring, as well as on the nitrogen, change the potency of compounds by over three orders
