NDDNI

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: NDDNI
• 英文别名: N-n-dodecylnicotinium iodide；1-dodecyl-3-[(2S)-1-methylpyrrolidin-2-yl]pyridin-1-ium;iodide
• 化学式: C₂₂H₃₉N₂*I
• 分子量: 458.47
• InChiKey: RSLCPVZCHBQILE-FTBISJDPSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  2.67
• 重原子数：
  25
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.77
• 拓扑面积：
  7.1
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  1-碘十二烷 、 烟碱 在 溶剂黄146 作用下， 生成 NDDNI
  参考文献：
  名称：

  Development of subtype-selective ligands as antagonists at nicotinic receptors mediating nicotine-evoked dopamine release

  摘要：

  N-n-Alkylation of nicotine converts it from an agonist into an antagonist at neuronal nicotinic acetylcholine receptor subtypes mediating nicotine-evoked dopamine release. Conformationally restricted analogues exhibit both high affinity and selectivity at this site, and are able to access the brain due to their ability to act as substrates for the blood-brain barrier choline transporter. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2003.10.074

文献信息

• <i>N-n</i>-Alkylnicotinium Analogs, a Novel Class of Nicotinic Receptor Antagonists: Interaction with α4β2* and α7* Neuronal Nicotinic Receptors
  作者：Lincoln H. Wilkins、Vladimir P. Grinevich、Joshua T. Ayers、Peter A. Crooks、Linda P. Dwoskin

  DOI：10.1124/jpet.102.043349

  日期：2003.1.1

  subtype, with the exception of N-n-octylnicotinium iodide (NONI). The most potent analog was N-n-decylnicotinium iodide (NDNI; Ki = 90 nM). In contrast, none of the analogs in this series exhibited high affinity for the [3H]methyllycaconitine binding site, thus indicating low affinity for the alpha7* nAChR. The C8 analog, NONI, had low affinity for S-(-)-[3H]nicotine binding sites but was a potent inhibitor

  当前的研究表明，具有从1至12个碳原子增加的正烷基链长度的Nn-烷基烟碱类似物具有对大鼠纹状体膜中S-（-）-[3H]烟碱结合位点的不同亲和力（Ki = 90 nM-20 microM）。 。观察到线性关系，从而增加N-烷基链长提供了对α4beta2*烟碱乙酰胆碱受体（nAChR）亚型的亲和力，但Nn-辛基烟碱碘化物（NONI）除外。最有效的类似物是碘化N-癸基烟碱（NDNI； Ki = 90 nM）。相反，该系列中没有类似物对[3H]甲基lycaconitine结合位点表现出高亲和力，因此表明对α7* nAChR的亲和力低。C8类似物NONI 对S-（-）-[3H]烟碱结合位点具有低亲和力，但是S-（-）-烟碱诱发的[3H]多巴胺（DA）从融合的纹状体切片溢出的有效抑制剂（IC50 = 0.62 microM），从而证明了对介导S-（-）-尼古丁诱发的[3H] DA溢出的nAChR亚型的
• Development of subtype-selective ligands as antagonists at nicotinic receptors mediating nicotine-evoked dopamine release
  作者：Peter A Crooks、Joshua T Ayers、Rui Xu、Sangeetha P Sumithran、Vladimir P Grinevich、Lincoln H Wilkins、A.Gabriela Deaciuc、David D Allen、Linda P Dwoskin

  DOI：10.1016/j.bmcl.2003.10.074

  日期：2004.4

  N-n-Alkylation of nicotine converts it from an agonist into an antagonist at neuronal nicotinic acetylcholine receptor subtypes mediating nicotine-evoked dopamine release. Conformationally restricted analogues exhibit both high affinity and selectivity at this site, and are able to access the brain due to their ability to act as substrates for the blood-brain barrier choline transporter. (C) 2004 Elsevier Ltd. All rights reserved.
• Bifunctional compounds targeting both D2 and non-α7 nACh receptors: Design, synthesis and pharmacological characterization
  作者：Carlo Matera、Luca Pucci、Chiara Fiorentini、Sergio Fucile、Cristina Missale、Giovanni Grazioso、Francesco Clementi、Michele Zoli、Marco De Amici、Cecilia Gotti、Clelia Dallanoce

  DOI：10.1016/j.ejmech.2015.06.039

  日期：2015.8

  We designed, prepared and tested a set of structural analogs 1-4 as new hybrid compounds by incorporating, through a common alkyl chain of variable length, the pharmacophoric elements of N-n-allcyl nicotinium salts (non-alpha 7 nicotinic acetylcholine receptors antagonists) and of 7-hydroxy-2-(aminomethyl)chromanes (dopaminergic D-2 receptor agonists). The target compounds, which were assayed in binding experiments and electrophysiological, functional and Erk1/2 activation tests, essentially combined the pharmacological profiles of their individual receptor ligands. Among the studied derivatives, hybrid 2, one of the shortest homologs, in addition to the antagonist nicotinic profile similar to the other three congeners, behaved as a high affinity ligand at the investigated heteromeric nAChRs and as a low efficacy agonist at D(2)Rs. These bifunctional derivatives represent novel pharmacological tools in the study of nicotine addiction. (C) 2015 Elsevier Masson SAS. All rights reserved.