PROBES FOR NARCOTIC RECEPTOR MEDIATED PHENOMENA .7. SYNTHESIS AND PHARMACOLOGICAL PROPERTIES OF IRREVERSIBLE LIGANDS SPECIFIC FOR MU-OPIATE OR DELTA-OPIATE RECEPTORS
PROBES FOR NARCOTIC RECEPTOR MEDIATED PHENOMENA .7. SYNTHESIS AND PHARMACOLOGICAL PROPERTIES OF IRREVERSIBLE LIGANDS SPECIFIC FOR MU-OPIATE OR DELTA-OPIATE RECEPTORS
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DOI：
10.1021/jm00378a008
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发表时间：
1984-01-01
影响因子：
7.3
通讯作者：
KLEE, WA
中科院分区：
文献类型：
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作者：
BURKE, TR;BAJWA, BS;KLEE, WA
描述了基于芬太尼、内乙烯四氢东罂粟碱和依托尼氮碳骨架的阿片受体亲和试剂的合成。这些化合物中使用了异硫氰酸酯溴乙酰胺基和甲基富马酰胺基烷基化官能团，其中一些以前是.mu。具体的（12，[1-[2-（二乙氨基）乙基]-2-（4-乙氧基苄基）-5-异硫氰酸苯并咪唑]，BIT）和δ。特异性(8)[N-[1-[2-(4-异硫氰基苯基)乙基]-4-哌啶基]-N-苯基丙酰胺]，FIT和19[7.α.-(甲基富马酰胺)-6,14-内-乙烯四氢东罂粟碱]，FAO)体外。在小鼠热板试验中测定了标题化合物的镇痛活性，结果表明每一类中的某些化合物表现出吗啡样活性。还报道了NG108-15(δ受体)和大鼠脑膜(μ+δ受体)中阿片受体对[3H]Dalamid的结合EC50[中位有效浓度]值。通过此类实验，可以独立测量依托尼氮同系物 12-14 [5-(溴乙酰胺基)-1-[2-(二乙氨基)乙基]-2-(4-乙氧基苄基)苯并咪唑 (13) 和 1-[2-(二乙氨基)乙基]-2-(4-乙氧基苄基)-5-(甲基富莫酰胺基)苯并咪唑的表观亲和力(14)]为.mu。和.delta。受体。
Syntheses of affinity reagents for opiate receptors based on the fentanyl, endo-ethenotetrahydrooripavine and etonitazene carbon-nitrogen skeletons are described. The isothiocyanate bromoacetamido and methylfumaramido alkylating functions were employed in these compounds, some of which were previously .mu. specific (12, [1-[2-(diethylamino)ethyl]-2-(4-ethoxybenzyl)-5-isothiocyanatobenzimidazole], BIT) and .delta. specific (8) [N-[1-[2-(4-isothiocyanatophenyl)ethyl]-4-piperidinyl]-N-phenylpropanamide], FIT and 19 [7.alpha.-(methylfumaramido)-6, 14-endo-ethenotetrahydrooripavine], FAO) in vitro. Antinociceptive activity of the title compounds was determined in the mouse hot-plate test, which revealed that certain compounds in each class showed morphine-like activity. The binding EC50 [median effective concentration] values against [3H]Dalamid for opiate receptors in NG108-15 (.delta. receptors) and rat brain membranes (.mu. + .delta. receptors) are also reported. With this type of experiment, it was possible to independently measure the apparent affinity of the etonitazene congeners 12-14 [5-(bromoacetamido)-1-[2-(diethylamino)ethyl]-2-(4-ethoxybenzyl)benzimidazole (13) and 1-[2-(diethylamino)ethyl]-2-(4-ethoxybenzyl)-5-(methylfumoramido)benzimidazole (14)] for the .mu. and .delta. receptors.