Abstract
New growth hormone secretagogue (GHS) analogues were synthesized and evaluated for growth hormone releasing activity. This series derived from EP-51389 is based on a gem-diamino structure. Compounds that exhibited higher in vivo GH-releasing potency than hexarelin in rat (subcutaneous administration) were then tested per os in beagle dogs and for their binding affinity to human pituitary GHS receptors and to hGHS-R 1a. Compound 7 (JMV 1843, H-Aib-(d)-Trp-(d)-gTrp-formyl) showed high potency in these tests and was selected for clinical studies.(1)
MeSH terms
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Administration, Oral
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Adult
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Animals
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Animals, Newborn
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Binding, Competitive
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Cell Line
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Dogs
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Female
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Growth Hormone / metabolism*
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Humans
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In Vitro Techniques
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Indoles
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Injections, Subcutaneous
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Male
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Membranes
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Middle Aged
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Oligopeptides / chemical synthesis*
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Oligopeptides / chemistry
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Oligopeptides / pharmacology
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Pituitary Gland / metabolism
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Radioligand Assay
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Rats
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Rats, Sprague-Dawley
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Receptors, Cell Surface / metabolism
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Receptors, G-Protein-Coupled*
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Receptors, Ghrelin
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Tryptophan / analogs & derivatives
Substances
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Indoles
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Oligopeptides
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Receptors, Cell Surface
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Receptors, G-Protein-Coupled
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Receptors, Ghrelin
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macimorelin
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Tryptophan
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Growth Hormone