Highly Potent 4-Amino-indolo[2,3-c]azepin-3-one-Containing Somatostatin Mimetics with a Range of sst Receptor Selectivities
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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DOI：
10.1021/jm801205x
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发表时间：
2009-01-08
影响因子：
7.3
通讯作者：
Reubi, Jean Claude
中科院分区：
文献类型：
--
作者：
Feytens, Debby;De Vlaeminck, Magali;Reubi, Jean Claude
报道了含4-氨基吲哚并[2，3-c]氮杂卓-3-酮（Aia）的SRIF模拟物的合成、生物学评价和构象分析。不同的亚型选择性，观察到依赖于N-和C-末端取代基的D-Aia-Lys二肽模拟物。sst（5）-选择性类似物具有亚纳摩尔结合亲和力，是迄今为止报道的最有效的激动剂。还鉴定了具有高效力的非选择性模拟物。这项研究可以更好地定义生长激素抑制素药效团中必需的D-Trp侧链的生物活性构象。
The synthesis, biological evaluation, and conformational analysis of 4-amini-indolo[2,3-c]azepin-3-one (Aia)-containing SRIF mimetics are reported. Different subtype selectivities are observed depending on the Nand 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.