2-[N-酰基氨基（C1-C3）烷基]吲哚作为MT1褪黑素受体部分激动剂、拮抗剂和推定的反向激动剂。
2-[N-Acylamino(C1-C3)alkyl]indoles as MT1 melatonin receptor partial agonists, antagonists, and putative inverse agonists.
作者信息
Spadoni G, Balsamini C, Bedini A, Diamantini G, Di Giacomo B, Tontini A, Tarzia G, Mor M, Plazzi P V, Rivara S, Nonno R, Pannacci M, Lucini V, Fraschini F, Stankov B M
机构信息
Cattedra di Chemioterapia, Dipartimento di Farmacologia, Università degli Studi di Milano, Via Vanvitelli, 32, I-20129 Milano, Italy.
出版信息
J Med Chem. 1998 Sep 10;41(19):3624-34. doi: 10.1021/jm970721h.
The synthesis of several novel indole melatonin analogues substituted at the 2-position with acylaminomethyl (8-11), acylaminoethyl (5a-k), or acylaminopropyl (13) side chains is reported. On the basis of a novel in vitro functional assay (specific binding of [35S]GTPgammaS), which can discriminate agonist from partial agonist, antagonist, and inverse agonist ligands, 5a,g, h,j and 13 were shown to be partial agonists, 5d,e and 8-11 competitive antagonists, and 5b,c,k putative inverse agonists. Binding and functional assays were performed on cloned human MT1 receptor. Structure-activity relationship considerations indicate that N-[1-aryl-2-(4-methoxy-1H-indol-2-yl)(C1-C2)alkyl]alkanamides represent a lead structure for this type of ligands.
本文报道了几种新型吲哚类褪黑素类似物的合成，这些类似物在2位被酰氨基甲基（8 - 11）、酰氨基乙基（5a - k）或酰氨基丙基（13）侧链取代。基于一种新型体外功能测定法（[35S]GTPγS的特异性结合），该方法能够区分激动剂与部分激动剂、拮抗剂和反向激动剂配体，结果表明5a、g、h、j和13为部分激动剂，5d、e和8 - 11为竞争性拮抗剂，5b、c、k为推定的反向激动剂。对克隆的人MT1受体进行了结合和功能测定。构效关系研究表明，N - [1 - 芳基 - 2 - （4 - 甲氧基 - 1H - 吲哚 - 2 - 基）（C1 - C2）烷基]链烷酰胺代表了这类配体的先导结构。
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