344761-72-4Relevant academic research and scientific papers
Elucidation of structural elements for selectivity across monoamine transporters: Novel 2-[(diphenylmethyl)sulfinyl]acetamide (modafinil) analogues
Okunola-Bakare, Oluyomi M.,Cao, Jianjing,Kopajtic, Theresa,Katz, Jonathan L.,Loland, Claus J.,Shi, Lei,Newman, Amy Hauck
, p. 1000 - 1013 (2014/03/21)
2-[(Diphenylmethyl)sulfinyl]acetamide (modafinil, (±)-1) is a unique dopamine uptake inhibitor that binds the dopamine transporter (DAT) differently than cocaine and may have potential for the treatment of psychostimulant abuse. To further investigate structural requirements for this divergent binding mode, novel thio- and sulfinylacetamide and ethanamine analogues of (±)-1 were synthesized wherein (1) the diphenyl rings were substituted with methyl, trifluoromethyl, and halogen substituents and (2) substituents were added to the terminal amide/amine nitrogen. Halogen substitution of the diphenyl rings of (±)-1 gave several amide analogues with improved binding affinity for DAT and robust selectivity over the serotonin transporter (SERT), whereas affinity improved at SERT over DAT for the p-halo-substituted amine analogues. Molecular docking studies, using a subset of analogues with DAT and SERT homology models, and functional data obtained with DAT (A480T) and SERT (T497A) mutants defined a role for TM10 in the substrate/inhibitor S1 binding sites of DAT and SERT.
POTENT AND SELECTIVE INHIBITORS OF MONOAMINE TRANSPORTERS; METHOD OF MAKING; AND USE THEREOF
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Paragraph 0073; 0082, (2014/09/29)
Disclosed herein are bisarylmethylthioacetamides and bisarylmethylthioethylamines useful as inhibitors of monoamine transporters. The compounds are potent and/or selective inhibitors of dopamine (DA), serotonin (5-HT), and/or norepinephrine (NE) reuptake via their respective transporters, DAT, SERT and NET. Also disclosed are methods for eliciting a wake-promoting or cognitive or attention enhancing effect and for treating substance use disorders, attention deficit (hyperactivity) disorder, depressive disorders, bipolar disorder or other neuropsychiatric disorders sleep disorders or cognitive impairment using the compounds.
Simple synthesis of modafinil derivatives and their anti-inflammatory activity
Jung, Jae-Chul,Lee, Yeonju,Son, Jee-Young,Lim, Eunyoung,Jung, Mankil,Oh, Seikwan
, p. 10446 - 10458 (2012/11/07)
Simple synthesis of modafinil derivatives and their biological activity are described. The key synthetic strategies involve substitution and coupling reactions. We determined the anti-inflammatory effects of modafinil derivatives in cultured BV2 cells by measuring the inhibition of nitrite production and expression of iNOS and COX-2 after LPS stimulation. It was found that for sulfide analogues introduction of aliphatic groups on the amide part (compounds 11a-d) resulted in lower anti-inflammatory activity compared with cyclic or aromatic moieties (compounds 11e-k). However, for the sulfoxide analogues, introduction of aliphatic moieties (compounds 12a-d) showed higher anti-inflammatory activity than cyclic or aromatic fragments (compounds 12e-k) in BV-2 microglia cells.
SARs at the monoamine transporters for a novel series of modafinil analogues
Cao, Jianjing,Prisinzano, Thomas E.,Okunola, Oluyomi M.,Kopajtic, Theresa,Shook, Matthew,Katz, Jonathan L.,Newman, Amy Hauck
supporting information; experimental part, p. 48 - 52 (2011/04/22)
A series of modafinil (1) analogues were 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 dopamine transporter, serotonin transporter, and norepinephrine transporter 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.
