Abstract
The synthesis, biological evaluation, and conformational analysis of 4-amino-indolo[2,3-c]azepin-3-one (Aia)-containing SRIF mimetics are reported. Different subtype selectivities are observed depending on the N- and C-terminal substituents of the D-Aia-Lys dipeptide mimetic. An sst(5)-selective analogue with subnanomolar binding affinity was obtained that is the most potent agonist reported to date. A nonselective mimetic with high potency was also identified. This study allows a better definition of the bioactive conformation of the essential D-Trp side chain in the somatostatin pharmacophore.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amines / chemistry*
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Animals
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Azepines / chemical synthesis*
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Azepines / chemistry
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Azepines / metabolism*
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Biomimetic Materials / chemical synthesis
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Biomimetic Materials / chemistry
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Biomimetic Materials / metabolism
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Cell Line
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Cricetinae
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Humans
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Indoles / chemistry*
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Inhibitory Concentration 50
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Models, Molecular
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Molecular Structure
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Peptides / chemical synthesis
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Peptides / chemistry
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Peptides / metabolism
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Receptors, Somatostatin / metabolism*
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Somatostatin / chemistry*
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Somatostatin / metabolism*
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Structure-Activity Relationship
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Substrate Specificity
Substances
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Amines
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Azepines
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Indoles
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Peptides
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Receptors, Somatostatin
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Somatostatin