Abstract
A series of NN703 analogues with lysine mimetics combined with naphthyl- or biphenylalanine in the core has been prepared and tested in vitro in a rat pituitary cell based assay and subsequently in vivo in pigs in a single dose at 50 nmol/kg. Re-introduction of certain pharmacophores in the C-terminal of NN703, which were originally removed during optimisation for oral bioavailability, led to unexpectedly potent compounds in vitro as well as in vivo.
MeSH terms
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Administration, Oral
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Animals
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Biological Availability
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Cells, Cultured / cytology
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Cells, Cultured / metabolism
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Dipeptides / chemistry
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Dipeptides / metabolism
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Dipeptides / pharmacology*
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Growth Hormone / drug effects*
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Growth Hormone / metabolism
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Hormones / chemical synthesis
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Hormones / pharmacology*
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Indoles / chemistry
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Indoles / metabolism
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Indoles / pharmacology*
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Oligopeptides / chemical synthesis
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Oligopeptides / chemistry
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Oligopeptides / metabolism
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Oligopeptides / pharmacology*
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Pituitary Gland / cytology
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Rats
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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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Spiro Compounds / chemistry
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Spiro Compounds / metabolism
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Spiro Compounds / pharmacology*
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Structure-Activity Relationship
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Swine
Substances
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Dipeptides
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Hormones
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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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Spiro Compounds
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Growth Hormone
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tabimorelin
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ibutamoren mesylate
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ipamorelin