151889-03-1Relevant articles and documents
Mapping the Melatonin Receptor. 3. Design and Synthesis of Melatonin Agonists and Antagonists Derived from 2-Phenyltryptamines
Garratt, Peter J.,Jones, Rob,Tocher, Derek A.,Sugden, David
, p. 1132 - 1139 (1995)
Three series of 2-phenyltryptamides were prepared as melatonin analogues to investigate the nature of the binding site of the melatonin receptor in chicken brain and in Xenopus laevis melanophore cells.The 5-methoxy-2-phenyltryptamides (6a-j) have high bi
Convenient synthesis of melatonin analogues: 2- and 3-substituted -N-acetylindolylalkylamines
Nenajdenko, Valentine G.,Zakurdaev, Eugene P.,Prusov, Eugene V.,Balenkova, Elizabeth S.
, p. 11719 - 11724 (2007/10/03)
A new method for the synthesis of 2- and 3-substituted indolylalkylamides, derivatives of melatonin, from arylhydrazines and amidoketones by the Fischer reaction was elaborated. The amidoketones can be easily prepared from cyclic imines by reaction with acylpyridinium chloride. This method is a one-step synchronous creation of the selected alkylamide fragment and the indole core. Variation of the arylhydrazines create the desired substituents in the carbocycle of indolylalkylamides and suitable choice of amidoketone can direct the amidoalkyl chain to the 2- or 3-position of the indole. Graphical Abstract
Conformationally restrained melatonin analogues: Synthesis, binding affinity for the melatonin receptor, evaluation of the biological activity, and molecular modeling study
Spadoni, Gilberto,Balsamini, Cesarino,Diamantini, Giuseppe,Di Giacomo, Barbara,Tarzia, Giorgio,Mor, Marco,Plazzi, Pier Vincenzo,Rivara, Silvia,Lucini, Valeria,Nonno, Romolo,Pannacci, Marilou,Fraschini, Franco,Stankov, Bojidar Michaylov
, p. 1990 - 2002 (2007/10/03)
The design, synthesis, and biological profile of several indole melatonin analogues with a conformationally restricted C3 amidoethane side chain are presented. Examination of the accessible conformations of the melatonin side chain led us to explore some of its fully or partially restricted analogues, 2-12, the binding affinity values of which were utilized to gain further insight on the melatonin binding site. Two pharmacophoric models have been devised for melatonin and the active compounds by conformational analysis and superimposition performed using the DISCO program. In these models, the melatonin side chain can adopt a gauche/anti conformation out of the indole plane. Another contribution of this study regards the observation of a possible binding point interaction around the C2 position of the indole, as suggested by the remarkably increased binding affinity observed in the C2-substituted analogues 6 and 9 and especially in the more rigid analogue 5. The biological activity and the efficacy of the new compounds were tested by measuring the inhibition of the forskolin-stimulated cAMP accumulation and the GTPγS index. Both analyses demonstrated that all of the compounds were full agonists with the exception of 4 and 9, which showed a slight reduction in efficacy and would seem to be partial agonists.
