@article{63cd38f896344989967ef013d2aa336e,
title = "Structure-Activity Relationship Studies on a Series of 3α-[Bis(4-fluorophenyl)methoxy]tropanes and 3α-[Bis(4-fluorophenyl)methylamino]tropanes As Novel Atypical Dopamine Transporter (DAT) Inhibitors for the Treatment of Cocaine Use Disorders",
abstract = "The development of medications to treat cocaine use disorders has thus far defied success, leaving this patient population without pharmacotherapeutic options. As the dopamine transporter (DAT) plays a prominent role in the reinforcing effects of cocaine that can lead to addiction, atypical DAT inhibitors have been developed that prevent cocaine from binding to DAT, but they themselves are not cocaine-like. Herein, a series of novel DAT inhibitors were synthesized, and based on its pharmacological profile, the lead compound 10a was evaluated in phase I metabolic stability studies in mouse liver microsomes and compared to cocaine in locomotor activity and drug discrimination paradigms in mice. A molecular dynamic simulation study supported the hypothesis that atypical DAT inhibitors have similar binding poses at DAT in a conformation that differs from that of cocaine. Such differences may ultimately contribute to their unique behavioral profiles and potential for development as cocaine use disorder therapeutics.",
author = "Zou, {Mu Fa} and Jianjing Cao and Abramyan, {Ara M.} and Theresa Kopajtic and Claudio Zanettini and Guthrie, {Daryl A.} and Rana Rais and Slusher, {Barbara S.} and Lei Shi and Loland, {Claus J.} and Newman, {Amy Hauck}",
note = "Funding Information: Support for this research was provided to A.H.N., M.F.Z., J.C., T.K. J.K., A.M.A., D.A.G., and L.S. by the National Institute on Drug Abuse-Intramural Research Program (Z1A DA000389 21). C.J.L. is supported by the Danish Council for Independent Research (0602-02100B and 4183-00581). Care of the animals was in accordance with the guidelines of the National Institutes of Health and the National Institute on Drug Abuse Intramural Research Program Animal Care and Use Program, which is fully accredited by AAALAC International. Funding Information: Lone Rosenquist is thanked for excellent technical assistance. Support for this research was provided to A.H.N., M.F.Z., J.C., T.K., J.K., A.M.A., D.A.G., and L.S. by the National Institute on Drug AbuseIntramural Research Program (Z1A DA000389 21). C.J.L. is supported by the Danish Council for Independent Research (0602-02100B and 4183-00581). Care of the animals was in accordance with the guidelines of the National Institutes of Health and the National Institute on Drug Abuse Intramural Research Program Animal Care and Use Program, which is fully accredited by AAALAC International. Publisher Copyright: {\textcopyright} 2017 American Chemical Society.",
year = "2017",
month = dec,
day = "28",
doi = "10.1021/acs.jmedchem.7b01454",
language = "English (US)",
volume = "60",
pages = "10172--10187",
journal = "Journal of medicinal chemistry",
issn = "0022-2623",
publisher = "American Chemical Society",
number = "24",
}