Gmeiner P (2006)
Publication Type: Journal article
Publication year: 2006
Publisher: Elsevier
Book Volume: 14
Pages Range: 1949-1958
DOI: 10.1016/j.bmc.2005.10.042
Employing 1,3-dipolar cycloaddition for the synthesis of the 7a-azaindole nucleus, analogues of melatonin have been synthesized and tested against human and amphibian melatonin receptors. Introducing a phenyl substituent in position 2 of the heterocyclic moiety significantly increased binding affinity to both the MT1 and MT2 receptors. Shifting the methoxy group from position 5 to 2 of the 7a-azaindole ring led to a substantial reduction of MT1 binding when MT2 recognition was maintained. We theoretically investigated the hypothesis whether the 2-methoxy function of the azamelatonin analogue 27 is able to mimic the 5-methoxy group of the neurohormone by directing its 2-methoxy function toward the methoxy binding site. DFT calculations and experimental binding differences of analogue compounds indicate that the energy gained by forming the methoxy-specific hydrogen-bond interaction should exceed the energy required for adopting an alternative conformation. © 2005 Elsevier Ltd. All rights reserved.
APA:
Gmeiner, P. (2006). Bicyclic Melatonin Receptor Agonists Containing a Ring-junction Nitrogen: Synthesis, Biological Evaluation, and Molecular Modeling of the Putative Bioactive Conformation. Bioorganic & Medicinal Chemistry, 14, 1949-1958. https://doi.org/10.1016/j.bmc.2005.10.042
MLA:
Gmeiner, Peter. "Bicyclic Melatonin Receptor Agonists Containing a Ring-junction Nitrogen: Synthesis, Biological Evaluation, and Molecular Modeling of the Putative Bioactive Conformation." Bioorganic & Medicinal Chemistry 14 (2006): 1949-1958.
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