合成和生物评价1 - [1 - (2-benzo [b]噻吩基)环己基)哌啶同系物在dopamine-uptake和苯环己哌啶,sigma-binding网站。

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他Raymon LP XS,马特森MV, Eldefrawi我,德哥BR

合成和生物评价1 - [1 - (2-benzo [b]噻吩基)环己基)哌啶同系物在dopamine-uptake和苯环己哌啶,sigma-binding网站。

J地中海化学。1993年4月30日,36 (9):1188 - 93。

PubMed ID

8098066 (在PubMed

]

文摘

哌啶和环己基环同系物的高亲和性的多巴胺(DA)吸收抑制剂1 - (1 - (2-benzo [b]噻吩基)环己基)哌啶(一共3)都准备适当的环烷酮的四个步骤。这些化合物的能力进行测试,以取代[3 h]一共和[3 h]可卡因和抑制[3 h]对大鼠纹状体DA吸收匀浆。比例IC50 ([3 h]可卡因)/ IC50 ([3 h]一共)范围从62,一共1.5 1 -[2 -(苯并[b]噻吩基)-cyclopentylamine (17);可卡因给比率为0.6。这表明一共是最所有化合物的选择性检测网站[3 h]标记的一共而可卡因是最挑剔的网站[3 h]标记的可卡因。这些化合物的广泛能力的相对差异取代[3 h]一共和[3 h]可卡因表明这两个放射性配体是在运输标签不同的站点。一般而言,相关的化合物结构一共表现出更大的选择性网站[3 h]标记的一共。然而,一些BTCP-related衍生品显示更大的(相比之下,一共和可卡因)取代[3 h]可卡因的能力。最值得注意的是,1 - [1 - (2-benzo [b]噻吩基)环己基)吡咯烷(7)表现出更大的亲和力3.4倍相比,这些网站和一共9倍比可卡因更大的亲和力在这些网站。大部分的一共同系物显示更大的抑制能力[3 h] DA大鼠前脑突触体摄取比可卡因。 BTCP and 7 were the most potent of all the compounds tested in terms of their ability to inhibit uptake of [3H]DA. IC50 ratios for [3H]cocaine binding/[3H]DA uptake ranged from 0.47 for 1-[1-(2-benzo[b]thienyl)cyclopentyl]homopiperidine (11) to 8.8 for 1-(2-benzo[b]thienyl)cyclohexylamine (4). The importance of this ratio remains unclear in terms of identification of potential cocaine antagonists. As for BTCP, all of the compounds tested showed Ki values > 10,000 nM for displacement of [3H]TCP from rat brain homogenates. These compounds were able to displace the highly selective sigma receptor probe [3H]-(+)-pentazocine from guinea pig brain homogenates with Ki values ranging from 125 to 9170 nM. The significance of their sigma-binding activity in light of their dopaminergic properties is unclear. The diverse binding properties of these compounds at the DA-uptake site and their spectrum of inhibitory activities for [3H]DA uptake identifies them as a useful base for the development of subtype selective probes at this site. These compounds will allow further study of the structure and function of the "cocaine" receptor as well as the development of potential cocaine antagonists.

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绑定属性

药物	目标	财产	测量	pH值	温度(°C)
镇痛新	σ为靶标细胞内受体1	Ki (nM)	3.8	N /一个	N /一个	细节
苯环己哌啶	σ为靶标细胞内受体1	Ki (nM)	1767年	N /一个	N /一个	细节