New trisubstituted 1,2,4-triazoles as ghrelin receptor antagonists

被引：7
|
作者：
Blayo, Anne-Laure [1 ,2 ]
Maingot, Mathieu [1 ,2 ]
Aicher, Babette [3 ]
M'Kadmi, Celine [1 ,2 ]
Schmidt, Peter [3 ]
Mueller, Gilbert [3 ]
Teifel, Michael [3 ]
Guenther, Eckhard [3 ]
Gagne, Didier [1 ,2 ]
Denoyelle, Severine [1 ,2 ]
Martinez, Jean [1 ,2 ]
Fehrentz, Jean-Alain [1 ,2 ]
机构：
[1] Univ Montpellier I, CNRS, UMR 5247, Inst Biomol Max Mousseron, F-34093 Montpellier 5, France
[2] Univ Montpellier 2, Fac Pharm, F-34093 Montpellier 5, France
[3] Aeterna Zentaris GmbH, D-60314 Frankfurt, Germany
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2015年 / 25卷 / 01期
关键词：
1,2,4-Triazole scaffold; Structural modulation; GHS-R1a ghrelin receptor; Antagonists; SAR study; PHARMACOLOGICAL IN-VITRO; INDUCED LOCOMOTOR SENSITIZATION; GROWTH-HORMONE; VIVO EVALUATIONS; POTENT; RATS; DERIVATIVES; LIGANDS; OBESITY; PITUITARY;
D O I：
10.1016/j.bmcl.2014.11.031
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
Ghrelin receptor ligands based on a trisubstituted 1,2,4-triazole scaffold were recently synthesized and evaluated for their in vitro affinity for the GHS-R1a receptor and their biological activity. In this study, replacement of the alpha-aminoisobutyryl (Aib) moiety (a common feature present in numerous growth hormone secretagogues described in the literature) by aromatic and heteroaromatic groups was explored. We found potent antagonists incorporating the picolinic moiety in place of the Aib moiety. In an attempt to increase affinity and activity of our lead compound 2, we explored the modulation of the pyridine ring. Herein we report the design and the structure-activity relationships study of these new ghrelin receptor ligands. (C) 2014 Elsevier Ltd. All rights reserved.
引用
收藏
页码：20 / 24
页数：5
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