Synthesis and Pharmacological in Vitro and in Vivo Evaluations of Novel Triazole Derivatives as Ligands of the Ghrelin Receptor. 1
| العنوان: | Synthesis and Pharmacological in Vitro and in Vivo Evaluations of Novel Triazole Derivatives as Ligands of the Ghrelin Receptor. 1 |
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| المؤلفون: | Didier Gagne, Antonio Torsello, Aline Moulin, Jean Claude Galleyrand, Jean-Alain Fehrentz, Delphine Mousseaux, Daniel Perrissoud, Annie Heitz, Luc Demange, Damien Boeglin, Vittorio Locatelli, Jean Martinez, Gilbert Bergé, Joanne Ryan |
| المساهمون: | Demange, L, Boeglin, D, Moulin, A, Mousseaux, D, Ryan, J, Berge, G, Gagne, D, Heitz, A, Perrissoud, D, Locatelli, V, Torsello, A, Galleyrand, J, Fehrentz, J, Martinez, J |
| المصدر: | Journal of Medicinal Chemistry. 50:1939-1957 |
| بيانات النشر: | American Chemical Society (ACS), 2007. |
| سنة النشر: | 2007 |
| مصطلحات موضوعية: | Male, Agonist, medicine.drug_class, Pharmacology, Ligands, Partial agonist, Cell Line, Receptors, G-Protein-Coupled, Rats, Sprague-Dawley, Eating, Structure-Activity Relationship, Growth hormone secretagogue, In vivo, Drug Discovery, medicine, Animals, Combinatorial Chemistry Techniques, Humans, Receptors, Ghrelin, Receptor, BIO/14 - FARMACOLOGIA, Chemistry, Antagonist, Stereoisomerism, Triazoles, In vitro, Rats, Biochemistry, Growth Hormone, GHRELIN RECEPTOR, FOOD INTAKE, GH, Molecular Medicine, Calcium, Ghrelin |
| الوصف: | A new series of growth hormone secretagogue (GHS) analogues based on the 1,2,4-triazole structure were synthesized and evaluated for their in vitro binding and their ability to stimulate intracellular calcium release to the cloned hGHS-1a ghrelin receptor expressed in LLC PK-1 cells. We have synthesized potent ligands of this receptor, some of them behaving as agonists, partial agonists, or antagonists. Some compounds among the most potent, i.e., agonist 29c (JMV2873), partial agonists including 21b (JMV2810), antagonists 19b (JMV2866) and 19c (JMV2844), were evaluated for their in vivo activity on food intake, after sc injection in rodents. Some compounds were found to stimulate food intake like hexarelin; some others were identified as potent hexarelin antagonists in this assay. Among the tested compounds, 21b was identified as an in vitro ghrelin receptor partial agonist, as well as a potent in vivo antagonist of hexarelin-stimulated food intake in rodents. Compound 21b was without effect on GH release from rat. However, in this series of compounds, it was not possible to find a clear correlation between in vitro and in vivo results. |
| تدمد: | 1520-4804 0022-2623 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::117e0b6f6a59fc4f8a033f8f7d84d2c2Test https://doi.org/10.1021/jm070024hTest |
| حقوق: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....117e0b6f6a59fc4f8a033f8f7d84d2c2 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15204804 00222623 |
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