Elucidation of structural elements for selectivity across monoamine transporters: novel 2-[(diphenylmethyl)sulfinyl]acetamide (modafinil) analogues.
Elucidation of structural elements for selectivity across monoamine transporters: novel 2-[(diphenylmethyl)sulfinyl]acetamide (modafinil) analogues.
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DOI：
10.1021/jm401754x
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发表时间：
2014-02-13
影响因子：
7.3
通讯作者：
Newman AH
中科院分区：
文献类型：
--
作者：
Okunola-Bakare OM;Cao J;Kopajtic T;Katz JL;Loland CJ;Shi L;Newman AH
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.
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影响因子：
64.8
作者：
通讯作者：
--
影响因子：
7.3
作者：
Wilcken, Rainer;Zimmermann, Markus O.;Boeckler, Frank M.
通讯作者：
Boeckler, Frank M.
DOI：
10.1017/s1461145711000988
发表时间：
2012-08
期刊：
The international journal of neuropsychopharmacology
影响因子：
--
作者：
Reichel CM;See RE
通讯作者：
See RE
影响因子：
7.3
作者：
Agoston, GE;Wu, JH;Newman, AH
通讯作者：
Newman, AH
影响因子：
4.2
作者：
Cao, Jianjing;Prisinzano, Thomas E.;Okunola, Oluyomi M.;Kopajtic, Theresa;Shook, Matthew;Katz, Jonathan L.;Newman, Amy Hauck
通讯作者：
Newman, Amy Hauck