四氮杂芳族季铵盐：介导尼古丁诱发多巴胺释放的神经元烟碱受体新型亚型选择性拮抗剂。
Tetrakis-azaaromatic quaternary ammonium salts: novel subtype-selective antagonists at neuronal nicotinic receptors that mediate nicotine-evoked dopamine release.
作者信息
Zhang Zhenfa, Zheng Guangrong, Pivavarchyk Marharyta, Deaciuc A Gabriela, Dwoskin Linda P, Crooks Peter A
机构信息
Department of Pharmaceutical Sciences, University of Kentucky, Lexington, KY 40536-0082, USA.
出版信息
Bioorg Med Chem Lett. 2008 Nov 1;18(21):5753-7. doi: 10.1016/j.bmcl.2008.09.084. Epub 2008 Sep 26.
Abstract
A series of tetrakis-azaaromatic quaternary ammonium salts was synthesized to identify compounds with higher affinity and selectivity as antagonists at neuronal nicotinic receptor subtypes (nAChR) that mediate nicotine-evoked DA release. A high hit rate was achieved in identifying potent analogs that inhibit these nAChRs. Three tetrakis analogs, 11j, 11f, and 11g, were identified as potent (IC(50)=3, 28 and 56nM, respectively) antagonists at these receptors. These compounds represent a novel structural class of nicotinic receptor antagonists.
摘要
合成了一系列四氮杂芳族季铵盐，以鉴定对介导尼古丁诱发多巴胺释放的神经元烟碱样受体亚型（nAChR）具有更高亲和力和选择性的拮抗剂化合物。在鉴定抑制这些nAChR的有效类似物方面取得了很高的命中率。三种四氮类似物11j、11f和11g被鉴定为这些受体的强效拮抗剂（IC(50)分别为3、28和56 nM）。这些化合物代表了一类新型的烟碱样受体拮抗剂结构。
相似文献
1
Tetrakis-azaaromatic quaternary ammonium salts: novel subtype-selective antagonists at neuronal nicotinic receptors that mediate nicotine-evoked dopamine release.
Bioorg Med Chem Lett. 2008 Nov 1;18(21):5753-7. doi: 10.1016/j.bmcl.2008.09.084. Epub 2008 Sep 26.
2
Tris-azaaromatic quaternary ammonium salts: Novel templates as antagonists at nicotinic receptors mediating nicotine-evoked dopamine release.
Bioorg Med Chem Lett. 2007 Dec 15;17(24):6701-6. doi: 10.1016/j.bmcl.2007.10.062. Epub 2007 Oct 22.
3
Bis-azaaromatic quaternary ammonium salts as antagonists at nicotinic receptors mediating nicotine-evoked dopamine release: An investigation of binding conformation.
Bioorg Med Chem Lett. 2007 Dec 15;17(24):6734-8. doi: 10.1016/j.bmcl.2007.10.052. Epub 2007 Oct 18.
4
Novel bis-, tris-, and tetrakis-tertiary amino analogs as antagonists at neuronal nicotinic receptors that mediate nicotine-evoked dopamine release.
Bioorg Med Chem Lett. 2011 Jan 1;21(1):88-91. doi: 10.1016/j.bmcl.2010.11.070. Epub 2010 Nov 24.
5
bis-Azaaromatic quaternary ammonium analogues: ligands for alpha4beta2* and alpha7* subtypes of neuronal nicotinic receptors.
Bioorg Med Chem Lett. 2002 Nov 4;12(21):3067-71. doi: 10.1016/s0960-894x(02)00687-x.
6
QSAR modeling of mono- and bis-quaternary ammonium salts that act as antagonists at neuronal nicotinic acetylcholine receptors mediating dopamine release.
Bioorg Med Chem. 2006 May 1;14(9):3017-37. doi: 10.1016/j.bmc.2005.12.036. Epub 2006 Jan 20.
7
N-n-alkylpyridinium analogs, a novel class of nicotinic receptor antagonists: selective inhibition of nicotine-evoked [3H] dopamine overflow from superfused rat striatal slices.
J Pharmacol Exp Ther. 2003 Sep;306(3):1011-20. doi: 10.1124/jpet.103.051789. Epub 2003 May 23.
8
QSAR study on maximal inhibition (Imax) of quaternary ammonium antagonists for S-(-)-nicotine-evoked dopamine release from dopaminergic nerve terminals in rat striatum.
Bioorg Med Chem. 2009 Jul 1;17(13):4477-85. doi: 10.1016/j.bmc.2009.05.010. Epub 2009 May 8.
9
N-n-alkylnicotinium analogs, a novel class of nicotinic receptor antagonists: interaction with alpha4beta2* and alpha7* neuronal nicotinic receptors.
J Pharmacol Exp Ther. 2003 Jan;304(1):400-10. doi: 10.1124/jpet.102.043349.
10
N-n-alkylnicotinium analogs, a novel class of nicotinic receptor antagonist: inhibition of S(-)-nicotine-evoked [(3)H]dopamine overflow from superfused rat striatal slices.
J Pharmacol Exp Ther. 2002 Jun;301(3):1088-96. doi: 10.1124/jpet.301.3.1088.
引用本文的文献
1
Characterizing the Access of Cholinergic Antagonists to Efferent Synapses in the Inner Ear.
Front Neurosci. 2021 Dec 14;15:754585. doi: 10.3389/fnins.2021.754585. eCollection 2021.
2
Scientific overview: 2013 BBC plenary symposium on tobacco addiction.
Drug Alcohol Depend. 2014 Aug 1;141:107-17. doi: 10.1016/j.drugalcdep.2014.05.013. Epub 2014 Jun 2.
3
Nicotinic receptor antagonists as treatments for nicotine abuse.
Adv Pharmacol. 2014;69:513-51. doi: 10.1016/B978-0-12-420118-7.00013-5.
4
Novel small molecule α9α10 nicotinic receptor antagonist prevents and reverses chemotherapy-evoked neuropathic pain in rats.
Anesth Analg. 2012 Sep;115(3):713-20. doi: 10.1213/ANE.0b013e31825a3c72. Epub 2012 May 18.
5
The novel small molecule α9α10 nicotinic acetylcholine receptor antagonist ZZ-204G is analgesic.
Eur J Pharmacol. 2011 Nov 30;670(2-3):500-8. doi: 10.1016/j.ejphar.2011.08.053. Epub 2011 Sep 17.
6
Discovery of non-peptide, small molecule antagonists of α9α10 nicotinic acetylcholine receptors as novel analgesics for the treatment of neuropathic and tonic inflammatory pain.
Bioorg Med Chem Lett. 2011 Apr 15;21(8):2476-9. doi: 10.1016/j.bmcl.2011.02.043. Epub 2011 Feb 23.
7
Novel bis-, tris-, and tetrakis-tertiary amino analogs as antagonists at neuronal nicotinic receptors that mediate nicotine-evoked dopamine release.
Bioorg Med Chem Lett. 2011 Jan 1;21(1):88-91. doi: 10.1016/j.bmcl.2010.11.070. Epub 2010 Nov 24.
8
Novel bis-2,2,6,6-tetramethylpiperidine (bis-TMP) and bis-mecamylamine antagonists at neuronal nicotinic receptors mediating nicotine-evoked dopamine release.
Bioorg Med Chem Lett. 2010 Feb 15;20(4):1420-3. doi: 10.1016/j.bmcl.2009.12.089. Epub 2010 Jan 4.
本文引用的文献
1
N,N'-Alkane-diyl-bis-3-picoliniums as nicotinic receptor antagonists: inhibition of nicotine-evoked dopamine release and hyperactivity.
J Pharmacol Exp Ther. 2008 Aug;326(2):563-76. doi: 10.1124/jpet.108.136630. Epub 2008 May 6.
2
Tris-azaaromatic quaternary ammonium salts: Novel templates as antagonists at nicotinic receptors mediating nicotine-evoked dopamine release.
Bioorg Med Chem Lett. 2007 Dec 15;17(24):6701-6. doi: 10.1016/j.bmcl.2007.10.062. Epub 2007 Oct 22.
3
Carrier-mediated transport of the quaternary ammonium neuronal nicotinic receptor antagonist n,n'-dodecylbispicolinium dibromide at the blood-brain barrier.
J Pharmacol Exp Ther. 2008 Jan;324(1):244-50. doi: 10.1124/jpet.107.130906. Epub 2007 Oct 5.
4
Effect of a novel nicotinic receptor antagonist, N,N'-dodecane-1,12-diyl-bis-3-picolinium dibromide, on nicotine self-administration and hyperactivity in rats.
Psychopharmacology (Berl). 2006 Mar;184(3-4):426-34. doi: 10.1007/s00213-005-0163-8. Epub 2005 Oct 12.
5
Expression of nigrostriatal alpha 6-containing nicotinic acetylcholine receptors is selectively reduced, but not eliminated, by beta 3 subunit gene deletion.
Mol Pharmacol. 2005 Jun;67(6):2007-15. doi: 10.1124/mol.105.011940. Epub 2005 Mar 4.
6
Subunit composition and pharmacology of two classes of striatal presynaptic nicotinic acetylcholine receptors mediating dopamine release in mice.
Mol Pharmacol. 2004 Jun;65(6):1526-35. doi: 10.1124/mol.65.6.1526.
7
Getting past the asterisk: the subunit composition of presynaptic nicotinic receptors that modulate striatal dopamine release.
Mol Pharmacol. 2004 Jun;65(6):1333-5. doi: 10.1124/mol.65.6.1333.
8
Development of subtype-selective ligands as antagonists at nicotinic receptors mediating nicotine-evoked dopamine release.
Bioorg Med Chem Lett. 2004 Apr 19;14(8):1869-74. doi: 10.1016/j.bmcl.2003.10.074.
9
Subtype-selective nicotinic receptor antagonists: potential as tobacco use cessation agents.
Bioorg Med Chem Lett. 2004 Apr 19;14(8):1863-7. doi: 10.1016/j.bmcl.2003.10.073.
10
N-n-alkylnicotinium analogs, a novel class of nicotinic receptor antagonists: interaction with alpha4beta2* and alpha7* neuronal nicotinic receptors.
J Pharmacol Exp Ther. 2003 Jan;304(1):400-10. doi: 10.1124/jpet.102.043349.
Zotero 插件