Structure-activity studies of beta-carboline analogs.
Structure-activity studies of beta-carboline analogs.
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β-咔啉类似物的结构-活性研究。
DOI：
10.1016/0024-3205(84)90365-5
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发表时间：
1984
期刊：
影响因子：
6.1
通讯作者：
Toll,L
中科院分区：
文献类型：
--
作者：
Lawson,JA;Uyeno,ET;Nienow,J;Loew,GH;Toll,L
已经获得或合成了许多β-碳碱类似物，并测定了它们的体外受体亲和力和体内拮抗剂活性。选择类似物是为了探索n9 - h、芳香氮和c3 -酯部分对该类苯二氮卓类拮抗剂的高受体亲和力和拮抗剂活性的重要性。在研究的类似物中，我们描述了3-氰基-β-卡波林（lh）的性质，这是第一个在c3位置没有羰基的有效β-卡波林拮抗剂。结果表明：(1)c3取代基与关键阳离子受体位点的特异性相互作用而不是吸电子性质对于高受体亲和力和拮抗剂活性是重要的。(2)原子氮与阳离子受体位点的特异性面内相互作用，而不是与受体的中性芳香残基堆积，对于高亲和力和拮抗剂活性也很重要。(3)虽然n9H的存在增强了受体的亲和力，但与阴离子受体位点的相互作用似乎不是拮抗剂活性所必需的。
A number of β-carboline analogs have been obtained or synthesized, and their in vitro receptor affinities and in vivo antagonist activities determined. The choice of analogs was made in order to explore the importance of the N 9-H, the aromatic nitrogen and the C 3-ester moiety for high-receptor affinity and antagonist activity of this class of benzodiazepine antagonist. Among the analogs investigated, we describe the properties of 3-cyano-β-carboline (lh), the first potent β-carboline antagonist without a carbonyl at the C 3-position. The results obtained indicate:(1) Specific interactions of the C 3-substituent with key cationic receptor sites rather than electron-withdrawing properties are important for high-receptor affinity and antagonist activity.(2) Specific in-plane interactions of the atomatic nitrogen with a cationic receptor site, rather than stacking with neutral aromatic residues of the receptor are also important for high affinity and antagonist activity.(3) While the presence of an N 9 H enhances receptor affinity, interaction with an anionic receptor site does not appear essential for antagonist activity.