Elucidation of Structural Elements for Selectivity across Monoamine Transporters: Novel 2-[(Diphenylmethyl)sulfinyl]acetamide (Modafinil) Analogues

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Elucidation of Structural Elements for Selectivity across Monoamine Transporters: Novel 2-[(Diphenylmethyl)sulfinyl]acetamide (Modafinil) Analogues. / Okunola-Bakara, Oluyomi; Cao, Jianjing; Kopajtic, Theresa; Katz, Jonathan L.; Løland, Claus Juul; Shi, Lei; Newman, Amy Hauck.

In: Journal of Medicinal Chemistry, Vol. 57, No. 3, 2014, p. 1000-1013.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Okunola-Bakara, O, Cao, J, Kopajtic, T, Katz, JL, Løland, CJ, Shi, L & Newman, AH 2014, 'Elucidation of Structural Elements for Selectivity across Monoamine Transporters: Novel 2-[(Diphenylmethyl)sulfinyl]acetamide (Modafinil) Analogues', Journal of Medicinal Chemistry, vol. 57, no. 3, pp. 1000-1013. https://doi.org/10.1021/jm401754x

APA

Okunola-Bakara, O., Cao, J., Kopajtic, T., Katz, J. L., Løland, C. J., Shi, L., & Newman, A. H. (2014). Elucidation of Structural Elements for Selectivity across Monoamine Transporters: Novel 2-[(Diphenylmethyl)sulfinyl]acetamide (Modafinil) Analogues. Journal of Medicinal Chemistry, 57(3), 1000-1013. https://doi.org/10.1021/jm401754x

Vancouver

Okunola-Bakara O, Cao J, Kopajtic T, Katz JL, Løland CJ, Shi L et al. Elucidation of Structural Elements for Selectivity across Monoamine Transporters: Novel 2-[(Diphenylmethyl)sulfinyl]acetamide (Modafinil) Analogues. Journal of Medicinal Chemistry. 2014;57(3):1000-1013. https://doi.org/10.1021/jm401754x

Author

Okunola-Bakara, Oluyomi ; Cao, Jianjing ; Kopajtic, Theresa ; Katz, Jonathan L. ; Løland, Claus Juul ; Shi, Lei ; Newman, Amy Hauck. / Elucidation of Structural Elements for Selectivity across Monoamine Transporters: Novel 2-[(Diphenylmethyl)sulfinyl]acetamide (Modafinil) Analogues. In: Journal of Medicinal Chemistry. 2014 ; Vol. 57, No. 3. pp. 1000-1013.

Bibtex

@article{2189319ad7044b2c9aa8174048d268ce,
title = "Elucidation of Structural Elements for Selectivity across Monoamine Transporters: Novel 2-[(Diphenylmethyl)sulfinyl]acetamide (Modafinil) Analogues",
abstract = "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. ",
author = "Oluyomi Okunola-Bakara and Jianjing Cao and Theresa Kopajtic and Katz, {Jonathan L.} and L{\o}land, {Claus Juul} and Lei Shi and Newman, {Amy Hauck}",
year = "2014",
doi = "10.1021/jm401754x",
language = "English",
volume = "57",
pages = "1000--1013",
journal = "Journal of Medicinal Chemistry",
issn = "0022-2623",
publisher = "American Chemical Society",
number = "3",

}

RIS

TY - JOUR

T1 - Elucidation of Structural Elements for Selectivity across Monoamine Transporters: Novel 2-[(Diphenylmethyl)sulfinyl]acetamide (Modafinil) Analogues

AU - Okunola-Bakara, Oluyomi

AU - Cao, Jianjing

AU - Kopajtic, Theresa

AU - Katz, Jonathan L.

AU - Løland, Claus Juul

AU - Shi, Lei

AU - Newman, Amy Hauck

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

U2 - 10.1021/jm401754x

DO - 10.1021/jm401754x

M3 - Journal article

VL - 57

SP - 1000

EP - 1013

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

SN - 0022-2623

IS - 3

ER -

ID: 137196803