期刊
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
卷 86, 期 -, 页码 700-709出版社
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2014.09.038
关键词
Hexahydroindenopyridines; Melatonin; MT1 and MT2 receptor binding; Synthesis
资金
- Spanish Ministry of Economy and Competiveness [SAF2011-23777]
- European Regional Development Fund (FEDER)
- Generalitat Valenciana [GVACOMP2013-015, PROMETEO II/2013/014]
- Spanish Ministry of Education
Hexahydroindenopyridine (HHIP) is an interesting tricyclic piperidine nucleus that is structurally related to melatonin, a serotonin-derived neurohormone. Melatonin receptor ligands have applications in several cellular, neuroendocrine and neurophysiological disorders, including depression and/or insomnia. We report herein an efficient two-step method to prepare new HHIP via enamine C-alkylation-cyclization. The influence of substituents on the benzene ring and the nitrogen atom on melatoninergic receptors has been studied. Among the 25 synthesized HHIPs, some of them containing methylenedioxy (series 2) and 8-chloro-7-methoxy substituents (series 4) on the benzene ring revealed affinity for the MT1 and/or the MT2 receptors within the nanomolar range or low micromolar. Similar activities were also encountered for those presenting urea (4g), N-aryl (2e) and N-alkyl (2f) acetamide functions. Therefore, new synthesized compounds with a HHIP nucleus have emerged as new promising leads towards the discovery of melatoninergic ligands which could provide new therapeutic agents. (C) 2014 Elsevier Masson SAS. All rights reserved.
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