9-Aminomethyl-9,10-dihydroanthracene (AMDA) analogs as structural probes for steric tolerance in 5-HT2A and H1 receptor binding sites.

Shah JR; Mosier PD; Peddi

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9-Aminomethyl-9,10-dihydroanthracene (AMDA) analogs as structural probes for steric tolerance in 5-HT2A and H1 receptor binding sites.

机译：9-氨基甲基-9,10-二氢蒽（AMDA）类似物作为在5-HT2A和H1受体结合位点的空间耐受性的结构探针。

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Synthesis, radioligand binding and molecular modeling studies of several 9-aminomethyl-9,10-dihydroanthracene (AMDA) analogs were carried out to determine the extent of the steric tolerance associated with expansion of the tricyclic ring system and amine substitution at 5-HT(2A) and H(1) receptors. A mixture of (7,12-dihydrotetraphene-12-yl)methanamine and (6,11-dihydrotetracene-11-yl)methanamine in a 75-25% ratio was found to have an apparent K(i) of 10nM at the 5-HT(2A) receptor. A substantial binding affinity for (7,12-dihydrotetraphene-3-methoxy-12-yl)methanamine at the 5-HT(2A) receptor (K(i)=21 nM) was also observed. Interestingly, this compound was found to have 100-fold selectivity for 5-HT(2A) over the H(1) receptor (K(i)=2500 nM). N-Phenylalkyl-AMDA derivatives, in which the length of the alkyl chain varied from methylene to n-butylene, were found to have only weak affinity for both 5-HT(2A) and H(1) receptors (K(i)=223 to 964 nM). Our results show that large rigid annulated AMDA analogs can be sterically accommodated within the proposed 5-HT(2A) binding site.

机译：进行了几种9-氨基甲基-9,10-二氢蒽（AMDA）类似物的合成，放射性配体结合和分子建模研究，以确定与三环系统扩展和5-HT胺取代相关的空间耐受性程度2A）和H（1）受体。发现（7,12-二氢四苯并-12-基）甲胺和（6,11-二氢并四苯并-11-基）甲胺以75-25％的比例在5时的表观K（i）为10nM -HT（2A）受体。还观察到了对5-HT（2A）受体（K（i）= 21 nM）的（7,12-二氢四苯-3-甲氧基-12-基）甲胺的实质结合亲和力。有趣的是，发现该化合物对5-HT（2A）的选择性比H（1）受体高100倍（K（i）= 2500 nM）。发现烷基链的长度从亚甲基到正丁烯不等的N-苯基烷基-AMDA衍生物对5-HT（2A）和H（1）受体都只有较弱的亲和力（K（i）= 223至964 nM）。我们的结果表明，大型刚性环状AMDA类似物可以在建议的5-HT（2A）结合位点内空间容纳。

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《Bioorganic and Medicinal Chemistry Letters》 |2010年第3期|共4页
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Shah JR; Mosier PD; Peddi;
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1. 9-Aminomethyl-9,10-dihydroanthracene (AMDA) analogs as structural probes for steric tolerance in 5-HT2A and H1 receptor binding sites. [J] . Shah JR, Mosier PD, Peddi Bioorganic and Medicinal Chemistry Letters . 2010,第3期

机译：9-氨基甲基-9,10-二氢蒽（AMDA）类似物作为在5-HT2A和H1受体结合位点的空间耐受性的结构探针。
2. Methoxy-substituted 9-aminomethyl-9,10-dihydroanthracene (AMDA) derivatives exhibit differential binding affinities at the 5-HT(2A) receptor. [J] . Dewkar GK, Peddi S, Mosier PD, Bioorganic and Medicinal Chemistry Letters . 2008,第19期

机译：甲氧基取代的9-氨基甲基-9,10-二氢蒽（AMDA）衍生物在5-HT（2A）受体上表现出不同的结合亲和力。
3. Synthesis, structure-affinity relationships, and modeling of AMDA analogs at 5-HT2A and H1 receptors: structural factors contributing to selectivity. [J] . Shah JR, Mosier PD, Roth BL Bioorganic and medicinal chemistry . 2009,第18期

机译：在5-HT2A和H1受体上的AMDA类似物的合成，结构亲和关系和建模：有助于选择性的结构性因素。
4. Active Analog Approach To Histamine H1 Receptor Antagonists [C] . Ritter, A., Gerula, . 2001

机译：组胺H1受体拮抗剂的主动模拟方法
5. Mapping the binding site of the 5-HT2A receptor using mutagenesis and ligand libraries: Insights into the molecular actions of psychedelics. [D] . McCorvy, John David. 2012

机译：使用诱变和配体库定位5-HT2A受体的结合位点：迷幻分子作用的见解。
6. 9-Aminomethyl-910-dihydroanthracene (AMDA) Analogs as Structural Probes for Steric Tolerance in 5-HT2A and H1 Receptor Binding Sites [O] . Jitesh R. Shah, Philip D. Mosier, Srinivas Peddi, -1

机译：9-氨基甲基-910-二氢蒽（amDa）类似物作为结构探针位阻容差在5-HT 2a和H1受体结合位点
7. Methoxy-substituted 9-aminomethyl-9,10-dihydroanthracene (AMDA) derivatives exhibit differential binding affinities at the 5-HT2A receptor [O] . Gajanan K. Dewkar, Srinivas Peddi, Philip D. Mosier, 2008

机译：甲氧基取代的9-氨基甲基-9,10-二羟基蒽（AMDA）衍生物在5-HT2A受体处表现出差异结合亲和力
8. Structural Models of the Nicotinic Acetylcholine Receptor and Its Toxin-Binding Sites. [R] . Guy, H. R. 1980

机译：烟碱乙酰胆碱受体及其毒素结合位点的结构模型。

9-Aminomethyl-9,10-dihydroanthracene (AMDA) analogs as structural probes for steric tolerance in 5-HT2A and H1 receptor binding sites.

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