Highly Potent 4-Amino-indolo[2,3-c]azepin-3-one-Containing Somatostatin Mimetics with a Range of sst Receptor Selectivities

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• 作者：Debby Feytens ; Magali De Vlaeminck ; Renzo Cescato ; Dirk Tourw ; Jean Claude Reubi
• 刊名：Journal of Medicinal Chemistry
• 出版年：2009
• 出版时间：January 8, 2009
• 年：2009
• 卷：52
• 期：1
• 页码：95-104
• 全文大小：313K
• 年卷期：v.52,no.1(January 8, 2009)
• ISSN：1520-4804

文摘

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 sst₅-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.