Novel Orally Active Growth Hormone Secretagogues
| العنوان: | Novel Orally Active Growth Hormone Secretagogues |
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| المؤلفون: | Kjeld Madsen, Jesper Lau, Birgit Sehested Hansen, Karin Kramer Nielsen, Thomas Kruse Hansen, Nils Langeland Johansen, Henning Thøgersen, Behrend F. Lundt, Peter H. Andersen, Michael Ankersen, Bernd Peschke, Kirsten Raun |
| المصدر: | Journal of Medicinal Chemistry. 41:3705-3714 |
| بيانات النشر: | American Chemical Society (ACS), 1998. |
| سنة النشر: | 1998 |
| مصطلحات موضوعية: | Male, Models, Molecular, medicine.medical_specialty, Magnetic Resonance Spectroscopy, Swine, Drug Evaluation, Preclinical, Administration, Oral, Biological Availability, Rats, Sprague-Dawley, Structure-Activity Relationship, chemistry.chemical_compound, Dogs, Pharmacokinetics, In vivo, Oral administration, Internal medicine, Drug Discovery, medicine, Animals, Potency, Structure–activity relationship, Ipamorelin, Molecular Mimicry, Hormones, Rats, Bioavailability, Endocrinology, chemistry, Growth Hormone, Pituitary Gland, Injections, Intravenous, Molecular Medicine, Female, Oligopeptides, Lead compound |
| الوصف: | A novel class of growth hormone-releasing compounds with a molecular weight in the range from 500 to 650 has been discovered. The aim of this study was to obtain growth hormone secretagogues with oral bioavailability. By a rational approach we were able to reduce the size of the lead compound ipamorelin (4) and simultaneously to reduce hydrogen-bonding potential by incorporation of backbone isosters while retaining in vivo potency in swine. A rat pituitary assay was used for screening of all compounds and to evaluate which compounds should be tested further for in vivo potency in swine and oral bioavailability, fpo, in dogs. Most of the tested compounds had fpo in the range of 10-55%. In vivo potency in swine after iv dosing is reported, and ED50 was found to be 30 nmol/kg of body weight for the most potent compound. |
| تدمد: | 1520-4804 0022-2623 |
| DOI: | 10.1021/jm980197u |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::33f483c6cf8fe3143ed56face8c2eed8 https://doi.org/10.1021/jm980197u |
| رقم الانضمام: | edsair.doi.dedup.....33f483c6cf8fe3143ed56face8c2eed8 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15204804 00222623 |
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| DOI: | 10.1021/jm980197u |