Novel and High Affinity 2-[(Diphenylmethyl)sulfinyl]acetamide (Modafinil) Analogues as Atypical Dopamine Transporter Inhibitors

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

Standard

Novel and High Affinity 2-[(Diphenylmethyl)sulfinyl]acetamide (Modafinil) Analogues as Atypical Dopamine Transporter Inhibitors. / Cao, Jianjing; Slack, Rachel D.; Bakare, Oluyomi M.; Burzynski, Caitlin; Rais, Rana; Slusher, Barbara S.; Kopajtic, Theresa; Bonifazi, Alessandro; Ellenberger, Michael P.; Yano, Hideaki; He, Yi; Bi, Guo-Hua; Xi, Zheng-Xiong; Loland, Claus J.; Newman, Amy Hauck.

In: Journal of Medicinal Chemistry, Vol. 59, No. 23, 08.12.2016, p. 10676-10691.

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

Harvard

Cao, J, Slack, RD, Bakare, OM, Burzynski, C, Rais, R, Slusher, BS, Kopajtic, T, Bonifazi, A, Ellenberger, MP, Yano, H, He, Y, Bi, G-H, Xi, Z-X, Loland, CJ & Newman, AH 2016, 'Novel and High Affinity 2-[(Diphenylmethyl)sulfinyl]acetamide (Modafinil) Analogues as Atypical Dopamine Transporter Inhibitors', Journal of Medicinal Chemistry, vol. 59, no. 23, pp. 10676-10691. https://doi.org/10.1021/acs.jmedchem.6b01373

APA

Cao, J., Slack, R. D., Bakare, O. M., Burzynski, C., Rais, R., Slusher, B. S., Kopajtic, T., Bonifazi, A., Ellenberger, M. P., Yano, H., He, Y., Bi, G-H., Xi, Z-X., Loland, C. J., & Newman, A. H. (2016). Novel and High Affinity 2-[(Diphenylmethyl)sulfinyl]acetamide (Modafinil) Analogues as Atypical Dopamine Transporter Inhibitors. Journal of Medicinal Chemistry, 59(23), 10676-10691. https://doi.org/10.1021/acs.jmedchem.6b01373

Vancouver

Cao J, Slack RD, Bakare OM, Burzynski C, Rais R, Slusher BS et al. Novel and High Affinity 2-[(Diphenylmethyl)sulfinyl]acetamide (Modafinil) Analogues as Atypical Dopamine Transporter Inhibitors. Journal of Medicinal Chemistry. 2016 Dec 8;59(23):10676-10691. https://doi.org/10.1021/acs.jmedchem.6b01373

Author

Cao, Jianjing ; Slack, Rachel D. ; Bakare, Oluyomi M. ; Burzynski, Caitlin ; Rais, Rana ; Slusher, Barbara S. ; Kopajtic, Theresa ; Bonifazi, Alessandro ; Ellenberger, Michael P. ; Yano, Hideaki ; He, Yi ; Bi, Guo-Hua ; Xi, Zheng-Xiong ; Loland, Claus J. ; Newman, Amy Hauck. / Novel and High Affinity 2-[(Diphenylmethyl)sulfinyl]acetamide (Modafinil) Analogues as Atypical Dopamine Transporter Inhibitors. In: Journal of Medicinal Chemistry. 2016 ; Vol. 59, No. 23. pp. 10676-10691.

Bibtex

@article{363a56ff3084438584124bbc32f11738,
title = "Novel and High Affinity 2-[(Diphenylmethyl)sulfinyl]acetamide (Modafinil) Analogues as Atypical Dopamine Transporter Inhibitors",
abstract = "The development of pharmacotherapeutic treatments of psychostimulant abuse has remained a challenge, despite significant efforts made toward relevant mechanistic targets, such as the dopamine transporter (DAT). The atypical DAT inhibitors have received attention due to their promising pharmacological profiles in animal models of cocaine and methamphetamine abuse. Herein, we report a series of modafinil analogues that have an atypical DAT inhibitor profile. We extended SAR by chemically manipulating the oxidation states of the sulfoxide and the amide functional groups, halogenating the phenyl rings, and/or functionalizing the terminal nitrogen with substituted piperazines, resulting in several novel leads such as 11b, which demonstrated high DAT affinity (Ki = 2.5 nM) and selectivity without producing concomitant locomotor stimulation in mice, as compared to cocaine. These results are consistent with an atypical DAT inhibitor profile and suggest that 11b may be a potential lead for development as a psychostimulant abuse medication.",
author = "Jianjing Cao and Slack, {Rachel D.} and Bakare, {Oluyomi M.} and Caitlin Burzynski and Rana Rais and Slusher, {Barbara S.} and Theresa Kopajtic and Alessandro Bonifazi and Ellenberger, {Michael P.} and Hideaki Yano and Yi He and Guo-Hua Bi and Zheng-Xiong Xi and Loland, {Claus J.} and Newman, {Amy Hauck}",
year = "2016",
month = dec,
day = "8",
doi = "10.1021/acs.jmedchem.6b01373",
language = "English",
volume = "59",
pages = "10676--10691",
journal = "Journal of Medicinal Chemistry",
issn = "0022-2623",
publisher = "American Chemical Society",
number = "23",

}

RIS

TY - JOUR

T1 - Novel and High Affinity 2-[(Diphenylmethyl)sulfinyl]acetamide (Modafinil) Analogues as Atypical Dopamine Transporter Inhibitors

AU - Cao, Jianjing

AU - Slack, Rachel D.

AU - Bakare, Oluyomi M.

AU - Burzynski, Caitlin

AU - Rais, Rana

AU - Slusher, Barbara S.

AU - Kopajtic, Theresa

AU - Bonifazi, Alessandro

AU - Ellenberger, Michael P.

AU - Yano, Hideaki

AU - He, Yi

AU - Bi, Guo-Hua

AU - Xi, Zheng-Xiong

AU - Loland, Claus J.

AU - Newman, Amy Hauck

PY - 2016/12/8

Y1 - 2016/12/8

N2 - The development of pharmacotherapeutic treatments of psychostimulant abuse has remained a challenge, despite significant efforts made toward relevant mechanistic targets, such as the dopamine transporter (DAT). The atypical DAT inhibitors have received attention due to their promising pharmacological profiles in animal models of cocaine and methamphetamine abuse. Herein, we report a series of modafinil analogues that have an atypical DAT inhibitor profile. We extended SAR by chemically manipulating the oxidation states of the sulfoxide and the amide functional groups, halogenating the phenyl rings, and/or functionalizing the terminal nitrogen with substituted piperazines, resulting in several novel leads such as 11b, which demonstrated high DAT affinity (Ki = 2.5 nM) and selectivity without producing concomitant locomotor stimulation in mice, as compared to cocaine. These results are consistent with an atypical DAT inhibitor profile and suggest that 11b may be a potential lead for development as a psychostimulant abuse medication.

AB - The development of pharmacotherapeutic treatments of psychostimulant abuse has remained a challenge, despite significant efforts made toward relevant mechanistic targets, such as the dopamine transporter (DAT). The atypical DAT inhibitors have received attention due to their promising pharmacological profiles in animal models of cocaine and methamphetamine abuse. Herein, we report a series of modafinil analogues that have an atypical DAT inhibitor profile. We extended SAR by chemically manipulating the oxidation states of the sulfoxide and the amide functional groups, halogenating the phenyl rings, and/or functionalizing the terminal nitrogen with substituted piperazines, resulting in several novel leads such as 11b, which demonstrated high DAT affinity (Ki = 2.5 nM) and selectivity without producing concomitant locomotor stimulation in mice, as compared to cocaine. These results are consistent with an atypical DAT inhibitor profile and suggest that 11b may be a potential lead for development as a psychostimulant abuse medication.

U2 - 10.1021/acs.jmedchem.6b01373

DO - 10.1021/acs.jmedchem.6b01373

M3 - Journal article

C2 - 27933960

VL - 59

SP - 10676

EP - 10691

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

SN - 0022-2623

IS - 23

ER -

ID: 170800965