2,4-Diaminopyrimidine Derivatives as Potent Growth Hormone Secretagogue Receptor Antagonists
| Autor: | Verlyn G. Schaefer, Michael D. Serby, Bo Liu, Christine A. Collins, H. Douglas Falls, Hongyu Zhao, Eugene N. Bush, Victoria Knourek-Segel, Theresa M Turner, Michael E. Brune, Gang Liu, Thomas A. Fey, Wiweka Kaszubska, Brian A. Droz, Christi Kosogof, Zhili Xin, David W A Beno, Robin Shapiro, Peer B. Jacobson, Bruce G. Szczepankiewicz, Mei Liu, Nelson Lissa T, Hing L. Sham |
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| Rok vydání: | 2006 |
| Předmět: |
medicine.medical_specialty
Time Factors Growth hormone secretagogue receptor Drug Evaluation Preclinical CHO Cells Ligands Receptors G-Protein-Coupled Structure-Activity Relationship chemistry.chemical_compound Cricetinae Internal medicine Orexigenic Drug Discovery medicine Animals Humans Receptors Ghrelin Receptor Molecular Structure Chemistry digestive oral and skin physiology Antagonist Stereoisomerism Pyrimidines Endocrinology Diaminopyrimidine Anorectic Molecular Medicine Ghrelin hormones hormone substitutes and hormone antagonists Hormone medicine.drug |
| Zdroj: | Journal of Medicinal Chemistry. 49:2568-2578 |
| ISSN: | 1520-4804 0022-2623 |
| DOI: | 10.1021/jm0510934 |
| Popis: | Ghrelin, a gut-derived orexigenic hormone, is an endogenous ligand of the growth hormone secretagogue receptor (GHS-R). Centrally administered ghrelin has been shown to cause hunger and increase food intake in rodents. Inhibition of ghrelin actions with ghrelin antibody, peptidyl GHS-R antagonists, and antisense oligonucleosides resulted in weight loss and food intake decrease in rodents. Here we report the effects of GHS-R antagonists, some of which were potent, selective, and orally bioavailable. A structure-activity relationship study led to the discovery of 8a, which was effective in decreasing food intake and body weight in several acute rat studies. |
| Databáze: | OpenAIRE |
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