Blayo Anne-Laure, Maingot Mathieu, Aicher Babette, M'Kadmi Céline, Schmidt Peter, Müller Gilbert, Teifel Michael, Günther Eckhard, Gagne Didier, Denoyelle Séverine, Martinez Jean, Fehrentz Jean-Alain
Institut des Biomolécules Max Mousseron (IBMM), UMR 5247, CNRS-Université Montpellier I et Université Montpellier II, BP 14491, Faculté de Pharmacie, bât. E, 3(ème) étage, 15 avenue Charles Flahault, 34093 Montpellier Cedex 5, France.
Æterna Zentaris GmbH, Weismuellerstrasse 50, 60314 Frankfurt am Main, Germany.
Bioorg Med Chem Lett. 2015 Jan 1;25(1):20-4. doi: 10.1016/j.bmcl.2014.11.031. Epub 2014 Nov 15.
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 α-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.
最近合成了基于三取代1,2,4-三唑支架的胃饥饿素受体配体，并对其对GHS-R1a受体的体外亲和力及其生物活性进行了评估。在本研究中，探索了用芳香族和杂芳香族基团取代α-氨基异丁酰基（Aib）部分（文献中描述的众多生长激素促分泌素中存在的共同特征）。我们发现了用吡啶甲酸部分取代Aib部分的强效拮抗剂。为了提高我们的先导化合物2的亲和力和活性，我们探索了吡啶环的修饰。在此，我们报告这些新型胃饥饿素受体配体的设计和构效关系研究。
