新型莫达非尼（2-[(二苯甲基)亚磺酰基]乙酰胺）类似物单胺转运体的构效关系
Structure-Activity Relationships at the Monoamine Transporters for a Novel Series of Modafinil (2-[(diphenylmethyl)sulfinyl]acetamide) Analogues.
作者信息
Cao Jianjing, Prisinzano Thomas E, Okunola Oluyomi M, Kopajtic Theresa, Shook Matthew, Katz Jonathan L, Newman Amy Hauck
机构信息
Medicinal Chemistry, National Institute on Drug Abuse - Intramural Research Program, National Institutes of Health, 333 Cassell Drive, Baltimore, MD 21224.
出版信息
ACS Med Chem Lett. 2010 Oct 10;2(1):48-52. doi: 10.1021/ml1002025.
Abstract
A series of modafinil (1) analogues was synthesized wherein 1) para-halo-substitutents were added to the aryl rings, 2) the sulfoxide function was removed, and 3) the primary amide group was replaced with secondary and tertiary amides and amines to investigate the effects of these chemical modifications on DAT, SERT and NET binding. In addition, the locomotor-stimulant effects in mice of (±)-modafinil (1), its R- and S-enantiomers and its para-chloro sulfinylacetamide analogue (5c) were compared to those of cocaine.
摘要
合成了一系列莫达非尼（1）类似物，其中：1）在芳环上添加对卤代取代基；2）去除亚砜官能团；3）将伯酰胺基团替换为仲酰胺、叔酰胺和胺，以研究这些化学修饰对多巴胺转运体（DAT）、5-羟色胺转运体（SERT）和去甲肾上腺素转运体（NET）结合的影响。此外，还比较了（±）-莫达非尼（1）、其R-和S-对映体及其对氯亚磺酰乙酰胺类似物（5c）在小鼠体内的运动刺激作用与可卡因的作用。
相似文献
1
Structure-Activity Relationships at the Monoamine Transporters for a Novel Series of Modafinil (2-[(diphenylmethyl)sulfinyl]acetamide) Analogues.
ACS Med Chem Lett. 2010 Oct 10;2(1):48-52. doi: 10.1021/ml1002025.
2
Elucidation of structural elements for selectivity across monoamine transporters: novel 2-[(diphenylmethyl)sulfinyl]acetamide (modafinil) analogues.
J Med Chem. 2014 Feb 13;57(3):1000-13. doi: 10.1021/jm401754x. Epub 2014 Feb 4.
3
Modafinil occupies dopamine and norepinephrine transporters in vivo and modulates the transporters and trace amine activity in vitro.
J Pharmacol Exp Ther. 2006 Nov;319(2):561-9. doi: 10.1124/jpet.106.106583. Epub 2006 Aug 2.
4
Novel and High Affinity 2-[(Diphenylmethyl)sulfinyl]acetamide (Modafinil) Analogues as Atypical Dopamine Transporter Inhibitors.
J Med Chem. 2016 Dec 8;59(23):10676-10691. doi: 10.1021/acs.jmedchem.6b01373. Epub 2016 Nov 28.
5
Structure-activity relationships for locomotor stimulant effects and monoamine transporter interactions of substituted amphetamines and cathinones.
Neuropharmacology. 2024 Mar 1;245:109827. doi: 10.1016/j.neuropharm.2023.109827. Epub 2023 Dec 27.
6
Structure-activity relationships for a series of (Bis(4-fluorophenyl)methyl)sulfinylethyl-aminopiperidines and -piperidine amines at the dopamine transporter: Bioisosteric replacement of the piperazine improves metabolic stability.
Eur J Med Chem. 2020 Dec 15;208:112674. doi: 10.1016/j.ejmech.2020.112674. Epub 2020 Aug 9.
7
Synthesis and biological evaluation of meperidine analogues at monoamine transporters.
J Med Chem. 2005 Mar 10;48(5):1336-43. doi: 10.1021/jm0401614.
8
R-modafinil (armodafinil): a unique dopamine uptake inhibitor and potential medication for psychostimulant abuse.
Biol Psychiatry. 2012 Sep 1;72(5):405-13. doi: 10.1016/j.biopsych.2012.03.022. Epub 2012 Apr 25.
9
Structure-activity relationship studies on a novel series of (S)-2beta-substituted 3alpha-[bis(4-fluoro- or 4-chlorophenyl)methoxy]tropane analogues for in vivo investigation.
J Med Chem. 2006 Oct 19;49(21):6391-9. doi: 10.1021/jm060762q.
10
Further structurally constrained analogues of cis-(6-benzhydrylpiperidin-3-yl)benzylamine with elucidation of bioactive conformation: discovery of 1,4-diazabicyclo[3.3.1]nonane derivatives and evaluation of their biological properties for the monoamine transporters.
J Med Chem. 2004 Oct 7;47(21):5101-13. doi: 10.1021/jm049796t.
引用本文的文献
1
RDS-04-010: a novel atypical DAT inhibitor that inhibits cocaine taking and seeking and itself has low abuse potential in experimental animals.
Transl Psychiatry. 2025 May 24;15(1):182. doi: 10.1038/s41398-025-03391-7.
2
RDS04-010: A novel atypical DAT inhibitor that inhibits cocaine taking and seeking and itself has low abuse potential in experimental animals.
Res Sq. 2024 Nov 12:rs.3.rs-5269973. doi: 10.21203/rs.3.rs-5269973/v1.
3
Modafinil, an atypical CNS stimulant?
Adv Pharmacol. 2024;99:287-326. doi: 10.1016/bs.apha.2023.10.006. Epub 2023 Nov 22.
4
Series of (([1,1'-Biphenyl]-2-yl)methyl)sulfinylalkyl Alicyclic Amines as Novel and High Affinity Atypical Dopamine Transporter Inhibitors with Reduced hERG Activity.
ACS Pharmacol Transl Sci. 2024 Jan 5;7(2):515-532. doi: 10.1021/acsptsci.3c00322. eCollection 2024 Feb 9.
5
Modifications to 1-(4-(2-Bis(4-fluorophenyl)methyl)sulfinyl)alkyl Alicyclic Amines That Improve Metabolic Stability and Retain an Atypical DAT Inhibitor Profile.
J Med Chem. 2024 Jan 11;67(1):709-727. doi: 10.1021/acs.jmedchem.3c02037. Epub 2023 Dec 20.
6
Pharmacokinetics of Novel Dopamine Transporter Inhibitor CE-123 and Modafinil with a Focus on Central Nervous System Distribution.
Int J Mol Sci. 2023 Nov 29;24(23):16956. doi: 10.3390/ijms242316956.
7
Enzymatic Resolution and Decarboxylative Functionalization of α-Sulfinyl Esters.
Chemistry. 2024 Feb 1;30(7):e202302996. doi: 10.1002/chem.202302996. Epub 2023 Dec 11.
8
An FSCV Study on the Effects of Targeted Typical and Atypical DAT Inhibition on Dopamine Dynamics in the Nucleus Accumbens Shell of Male and Female Mice.
ACS Chem Neurosci. 2023 Aug 2;14(15):2802-2810. doi: 10.1021/acschemneuro.3c00354. Epub 2023 Jul 19.
9
Are There Prevalent Sex Differences in Psychostimulant Use Disorder? A Focus on the Potential Therapeutic Efficacy of Atypical Dopamine Uptake Inhibitors.
Molecules. 2023 Jul 7;28(13):5270. doi: 10.3390/molecules28135270.
10
Discovery and Development of Monoamine Transporter Ligands.
Adv Neurobiol. 2023;30:101-129. doi: 10.1007/978-3-031-21054-9_4.
本文引用的文献
1
Modulatory effects of modafinil on neural circuits regulating emotion and cognition.
Neuropsychopharmacology. 2010 Sep;35(10):2101-9. doi: 10.1038/npp.2010.83. Epub 2010 Jun 16.
2
Dopamine transporter-related effects of modafinil in rhesus monkeys.
Psychopharmacology (Berl). 2010 Jun;210(3):439-48. doi: 10.1007/s00213-010-1839-2. Epub 2010 Apr 13.
3
Modafinil effects on reinstatement of methamphetamine seeking in a rat model of relapse.
Psychopharmacology (Berl). 2010 Jun;210(3):337-46. doi: 10.1007/s00213-010-1828-5. Epub 2010 Mar 30.
4
Modafinil does not serve as a reinforcer in cocaine abusers.
Drug Alcohol Depend. 2010 Jan 15;106(2-3):233-6. doi: 10.1016/j.drugalcdep.2009.09.002. Epub 2009 Sep 23.
5
Armodafinil.
CNS Drugs. 2009 Sep;23(9):793-803. doi: 10.2165/11203290-000000000-00000.
6
Modafinil: a useful medication for cocaine addiction? Review of the evidence from neuropharmacological, experimental and clinical studies.
Curr Drug Abuse Rev. 2008 Jun;1(2):213-21. doi: 10.2174/1874473710801020213.
7
Effects of modafinil on dopamine and dopamine transporters in the male human brain: clinical implications.
JAMA. 2009 Mar 18;301(11):1148-54. doi: 10.1001/jama.2009.351.
8
Evidence for the involvement of dopamine transporters in behavioral stimulant effects of modafinil.
J Pharmacol Exp Ther. 2009 May;329(2):738-46. doi: 10.1124/jpet.108.146142. Epub 2009 Feb 5.
9
A double-blind, placebo-controlled trial of modafinil (200 mg/day) for methamphetamine dependence.
Addiction. 2009 Feb;104(2):224-33. doi: 10.1111/j.1360-0443.2008.02437.x.
10
Efficient synthesis and biological evaluation of two modafinil analogues.
Bioorg Med Chem. 2008 Dec 1;16(23):9904-10. doi: 10.1016/j.bmc.2008.10.027. Epub 2008 Oct 17.
Zotero 插件