Synthesis and pharmacological evaluation of pentacyclic 6a,7-dihydrodiindole and 2,3-dihydrodiindole derivatives as novel melatoninergic ligands

被引：23

作者：

Attia, Mohamed I. ^{[1
]}

Witt-Enderby, Paula A. ^{[2
]}

Julius, Justin ^{[2
]}

机构：

[1] Univ Wurzburg, Inst Pharmaceut, Pharmaceut Chem Div, D-97074 Wurzburg, Germany

[2] Duquesne Univ, Sch Pharm, Dept Pharmacol Toxicol, Div Pharmaceut Sci, Pittsburgh, PA 15282 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2008年 / 16卷 / 16期

关键词：

6a; 7-dihydrodiindole; pentacyclic; melatoninergic ligands; nitrogen heterocycles;

D O I：

10.1016/j.bmc.2008.07.012

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The synthesis of novel melatonin analogues 3a and 4a-c designed as melatonin receptor ligands is described. Among the newly synthesized ligands, 2-((S)-2-hydroxymethylindolin-1-ylmethyl)-melatonin 4b displayed the highest affinity for MT1 receptors (K-i=9.8 nM) and for MT2 subtype (K-i=7.8 nM), whereas the rigid pentacyclic ligand 3 showed the highest selectivity towards the MT2 receptor subtype ( K-i=319.3 nM for MT1 and K-i=65.2 nM for MT2). (C) 2008 Elsevier Ltd. All rights reserved.

引用

页码：7654 / 7661

页数：8

共 17 条

[1] ALANINE A, 1998, Patent No. 846683
[2] Synthesis, NMR conformational analysis and pharmacological evaluation of 7,7a,13,14-tetrahydro-6H-cyclobuta[b]pyrimido[1,2-a:3,4-a′]diindole analogues as melatonin receptor ligands
Attia, Mohamed I.
Gueclue, Deniz
Hertlein, Barbara
Julius, Justin
Witt-Enderby, Paula A.
Zlotos, Darius P.
[J]. ORGANIC & BIOMOLECULAR CHEMISTRY, 2007, 5 (13) : 2129 - 2137
[3] Synthesis and pharmacological evaluation of 6a,7-dihydro-6H,13H-pyrazino[1,2-a;4,5-a′]diindole analogs as melatonin receptor ligands
Attia, Mohamed I.
Julius, Justin
Witt-Enderby, Paula A.
Zlotos, Darius P.
[J]. TETRAHEDRON, 2007, 63 (03) : 754 - 760
[4] Design, synthesis and biological activity of azasugar-based CD163 ectodomain shedding inhibitors
Attia, Mohamed I.
Timmermann, Meike
Hoegger, Petra
Herdeis, Claus
[J]. EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, 2007, 2007 (22) : 3669 - 3675
[5] CHO NR, 2005, Patent No. 2005051910
[6] Csernus V, 2003, NEUROENDOCRINOL LETT, V24, P404
[7] Fourtillan JB, 2000, BIOPHARM DRUG DISPOS, V21, P15, DOI 10.1002/1099-081X(200001)21:1<15::AID-BDD215>3.0.CO
[8] 2-H
[9] Attenuation in the evolution of experimental spinal cord trauma by treatment with melatonin
Genovese, T
Mazzon, E
Muià, C
Bramanti, P
De Sarro, A
Cuzzocrea, S
[J]. JOURNAL OF PINEAL RESEARCH, 2005, 38 (03) : 198 - 208
[10] Asymmetric deprotonations: Lithiation of N-(tert-butoxycarbonyl)indoline with sec-butyllithium/(-)-sparteine
Gross, KMB
Jun, YM
Beak, P
[J]. JOURNAL OF ORGANIC CHEMISTRY, 1997, 62 (22) : 7679 - 7689

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