通过对那藤宁的结构改造得到新型阿朴啡 5-HT2A 和 α1A 拮抗剂。
New aporphinoid 5-HT2A and α1A antagonists via structural manipulations of nantenine.
机构信息
Department of Chemistry, Hunter College, CUNY, New York, NY 10065, USA.
出版信息
Bioorg Med Chem. 2011 Oct 1;19(19):5861-8. doi: 10.1016/j.bmc.2011.08.019. Epub 2011 Aug 18.
Abstract
A series of C1, C2, C3 and N6 analogs of nantenine (2) was synthesized and evaluated in 5-HT(2A) and α(1A) receptor functional assays. Alkyl substitution of the C1 and N6 methyl groups of nantenine provided selective 5-HT(2A) and α(1A) antagonists, respectively. The C2 alkyloxy analogs studied were generally selective for α(1A) versus 5-HT(2A). The C3 bromo analog 15 is one of the most potent aporphinoid 5-HT(2A) antagonists known presently.
摘要
合成了一系列 C1、C2、C3 和 N6 去甲育亨宾类似物（2），并在 5-HT（2A）和α（1A）受体功能测定中进行了评价。去甲育亨宾的 C1 和 N6 甲基的烷基取代分别提供了选择性 5-HT（2A）和α（1A）拮抗剂。所研究的 C2 烷氧基类似物通常对α（1A）比对 5-HT（2A）具有选择性。C3 溴代类似物 15 是目前已知的最有效的阿朴啡类 5-HT（2A）拮抗剂之一。
相似文献
1
New aporphinoid 5-HT2A and α1A antagonists via structural manipulations of nantenine.
Bioorg Med Chem. 2011 Oct 1;19(19):5861-8. doi: 10.1016/j.bmc.2011.08.019. Epub 2011 Aug 18.
2
Evaluation of structural effects on 5-HT(2A) receptor antagonism by aporphines: identification of a new aporphine with 5-HT(2A) antagonist activity.
Bioorg Med Chem Lett. 2014 Apr 1;24(7):1664-7. doi: 10.1016/j.bmcl.2014.02.066. Epub 2014 Mar 4.
3
C4 phenyl aporphines with selective h5-HT(2B) receptor affinity.
Bioorg Med Chem Lett. 2015 Sep 1;25(17):3451-4. doi: 10.1016/j.bmcl.2015.07.012. Epub 2015 Jul 11.
4
Aporphinoid antagonists of 5-HT2A receptors: further evaluation of ring A substituents and the size of ring C.
Chem Biol Drug Des. 2014 Nov;84(5):558-66. doi: 10.1111/cbdd.12345. Epub 2014 Jun 3.
5
Synthesis and evaluation of aporphine analogs containing C1 allyl isosteres at the h5-HT(2A) receptor.
Bioorg Med Chem Lett. 2015 Nov 15;25(22):5102-6. doi: 10.1016/j.bmcl.2015.10.012. Epub 2015 Oct 9.
6
(+/-)-Nantenine analogs as antagonists at human 5-HT(2A) receptors: C1 and flexible congeners.
Bioorg Med Chem Lett. 2009 May 1;19(9):2530-2. doi: 10.1016/j.bmcl.2009.03.048. Epub 2009 Mar 16.
7
Affinity of aporphines for the human 5-HT2A receptor: insights from homology modeling and molecular docking studies.
Bioorg Med Chem. 2010 Aug 1;18(15):5562-75. doi: 10.1016/j.bmc.2010.06.043. Epub 2010 Jun 20.
8
In vitro functional evaluation of isolaureline, dicentrine and glaucine enantiomers at 5-HT and α receptors.
Chem Biol Drug Des. 2019 Feb;93(2):132-138. doi: 10.1111/cbdd.13390. Epub 2018 Oct 3.
9
Discovery of novel potent and selective ligands for 5-HT2A receptor with quinazoline scaffold.
Bioorg Med Chem Lett. 2015 Sep 15;25(18):3970-4. doi: 10.1016/j.bmcl.2015.07.030. Epub 2015 Jul 18.
10
Synthetic studies and pharmacological evaluations on the MDMA ('Ecstasy') antagonist nantenine.
Bioorg Med Chem Lett. 2010 Jan 15;20(2):628-31. doi: 10.1016/j.bmcl.2009.11.053. Epub 2009 Nov 20.
引用本文的文献
1
Total Synthesis of Aporphine Alkaloids via Photocatalytic Oxidative Phenol Coupling and Biological Evaluation at the Serotonin 5-HT and Adrenergic α Receptors.
J Med Chem. 2025 Jul 24;68(14):14628-14644. doi: 10.1021/acs.jmedchem.5c00771. Epub 2025 Jul 7.
2
N-Arylsulfonylated C-Homoaporphines as a New Class of Antiplatelet and Antimicrobial Agents.
ACS Med Chem Lett. 2024 Dec 23;16(1):116-125. doi: 10.1021/acsmedchemlett.4c00491. eCollection 2025 Jan 9.
3
Structure-activity profiling of alkaloid natural product pharmacophores against a Schistosoma serotonin receptor.
Int J Parasitol Drugs Drug Resist. 2018 Dec;8(3):550-558. doi: 10.1016/j.ijpddr.2018.09.001. Epub 2018 Sep 28.
4
Synthesis and evaluation of nuciferine and roemerine enantiomers as 5-HT and α receptor antagonists.
Medchemcomm. 2018 Feb 26;9(3):576-582. doi: 10.1039/c7md00629b. eCollection 2018 Mar 1.
5
Synthesis and evaluation of aporphine analogs containing C1 allyl isosteres at the h5-HT(2A) receptor.
Bioorg Med Chem Lett. 2015 Nov 15;25(22):5102-6. doi: 10.1016/j.bmcl.2015.10.012. Epub 2015 Oct 9.
6
C4 phenyl aporphines with selective h5-HT(2B) receptor affinity.
Bioorg Med Chem Lett. 2015 Sep 1;25(17):3451-4. doi: 10.1016/j.bmcl.2015.07.012. Epub 2015 Jul 11.
7
Aporphinoid antagonists of 5-HT2A receptors: further evaluation of ring A substituents and the size of ring C.
Chem Biol Drug Des. 2014 Nov;84(5):558-66. doi: 10.1111/cbdd.12345. Epub 2014 Jun 3.
8
Evaluation of structural effects on 5-HT(2A) receptor antagonism by aporphines: identification of a new aporphine with 5-HT(2A) antagonist activity.
Bioorg Med Chem Lett. 2014 Apr 1;24(7):1664-7. doi: 10.1016/j.bmcl.2014.02.066. Epub 2014 Mar 4.
9
A New Route to Azafluoranthene Natural Products via Direct Arylation.
European J Org Chem. 2013 Feb 1;3013(6):1107-1115. doi: 10.1002/ejoc.201201190. Epub 2013 Jan 3.
本文引用的文献
1
Further SAR study on 11-O-substituted aporphine analogues: identification of highly potent dopamine D3 receptor ligands.
Bioorg Med Chem. 2011 Mar 15;19(6):1999-2008. doi: 10.1016/j.bmc.2011.01.053. Epub 2011 Jan 31.
2
Involvement of 5-HT2A receptors in MDMA reinforcement and cue-induced reinstatement of MDMA-seeking behaviour.
Int J Neuropsychopharmacol. 2011 Aug;14(7):927-40. doi: 10.1017/S1461145710001215. Epub 2010 Oct 14.
3
Dantrolene in the treatment of MDMA-related hyperpyrexia: a systematic review.
CJEM. 2010 Sep;12(5):435-42. doi: 10.1017/s1481803500012598.
4
Anti-tubercular screening of natural products from Colombian plants: 3-methoxynordomesticine, an inhibitor of MurE ligase of Mycobacterium tuberculosis.
J Antimicrob Chemother. 2010 Oct;65(10):2101-7. doi: 10.1093/jac/dkq313. Epub 2010 Aug 18.
5
Affinity of aporphines for the human 5-HT2A receptor: insights from homology modeling and molecular docking studies.
Bioorg Med Chem. 2010 Aug 1;18(15):5562-75. doi: 10.1016/j.bmc.2010.06.043. Epub 2010 Jun 20.
6
Nantenine as an acetylcholinesterase inhibitor: SAR, enzyme kinetics and molecular modeling investigations.
J Enzyme Inhib Med Chem. 2011 Feb;26(1):46-55. doi: 10.3109/14756361003671078. Epub 2010 Jun 28.
7
Microwave-Assisted Direct Biaryl Coupling: First Application to the Synthesis of Aporphines.
Tetrahedron Lett. 2009 May 20;50(20):2437-2439. doi: 10.1016/j.tetlet.2009.03.029.
8
Synthesis of dihydrofuroaporphine derivatives: identification of a potent and selective serotonin 5-HT 1A receptor agonist.
J Med Chem. 2010 Feb 11;53(3):1319-28. doi: 10.1021/jm9015763.
9
Synthetic studies and pharmacological evaluations on the MDMA ('Ecstasy') antagonist nantenine.
Bioorg Med Chem Lett. 2010 Jan 15;20(2):628-31. doi: 10.1016/j.bmcl.2009.11.053. Epub 2009 Nov 20.
10
Use of apomorphine in Parkinson's disease.
Neurol Sci. 2008 Dec;29 Suppl 5:S383-6. doi: 10.1007/s10072-008-1053-8.
Zotero 插件