Structure-activity relationship studies of highly selective inhibitors of the dopamine transporter:: N-benzylpiperidine analogues of 1-[2-[bis(4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperazine

被引：19

作者：

Greiner, E

Prisinzano, T

Johnson, EM

Dersch, CM

Marcus, J

Partilla, JS

Rothman, RB

Jacobson, AE

Rice, KC

机构：

[1] NIDDKD, Med Chem Lab, NIH, Bethesda, MD 20892 USA

[2] NIDA, Addict Res Ctr, Clin Psychopharmacol Sect, DHHS, Baltimore, MD 21224 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2003年 / 46卷 / 08期

关键词：

D O I：

10.1021/jm020419v

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of 4-[2-[bis(4-fluorophenyl)methoxylethyl-1-benzylpiperidines were examined for their ability to bind to the dopamine transporter (DAT), the serotonin transporter (SERT), and the norepinephrine transporter (NET). Binding results indicated that the presence of an electron-withdrawing group in the C-4-position of the N-benzyl group is beneficial for binding to the DAT. Several analogues have been identified with high affinity for the DAT, up to 500-fold selectivity over the SERT and about 170-fold selectivity over the NET in binding and uptake inhibition assays.

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页码：1465 / 1469

页数：5

相关论文

共 22 条

[1] THE DOPAMINE UPTAKE INHIBITOR GBR 12909 - SELECTIVITY AND MOLECULAR MECHANISM OF ACTION [J].

ANDERSEN, PH .

EUROPEAN JOURNAL OF PHARMACOLOGY, 1989, 166 (03) :493-504

[2]

BERGMAN J, 1989, J PHARMACOL EXP THER, V251, P150

[3] Expansion of structure-activity studies of piperidine analogues of 1-[2-(diphenylmethoxy)ethyl]-4-(3-phenylpropyl)piperazine (GBR 12935) compounds by altering substitutions in the N-benzyl moiety and behavioral pharmacology of selected molecules [J].

Dutta, AK ;

Davis, MC ;

Fei, XS ;

Beardsley, PM ;

Cook, CD ;

Reith, MEA .

JOURNAL OF MEDICINAL CHEMISTRY, 2002, 45 (03) :654-662

[4] Structure-activity relationship studies of 4-[2-(diphenylmethoxy)ethyl]-1-benzylpiperidine derivatives and their N-analogues: Evaluation of behavioral activity of O- and N-analogues and their binding to monoamine transporters [J].

Dutta, AK ;

Fei, XS ;

Beardsley, PM ;

Newman, JL ;

Reith, MEA .

JOURNAL OF MEDICINAL CHEMISTRY, 2001, 44 (06) :937-948

[5] Highly selective, novel analogs of 4-[2-(diphenylmethoxy)ethyl]-1-benzylpiperidine for the dopamine transporter: Effect of different aromatic substitutions on their affinity and selectivity [J].

Dutta, AK ;

Coffey, LL ;

Reith, MEA .

JOURNAL OF MEDICINAL CHEMISTRY, 1997, 40 (01) :35-43

[6] Structure-activity relationship studies of novel 4-[2-[bis(4-fluorophenyl)methoxy]ethyl]-1-(3-phenylpropyl)piperidine analogs: Synthesis and biological evaluation at the dopamine and serotonin transporter sites [J].

Dutta, AK ;

Xu, C ;

Reith, MEA .

JOURNAL OF MEDICINAL CHEMISTRY, 1996, 39 (03) :749-756

[7]

DUTTA AK, 1993, MED CHEM RES, V3, P209

[8] Sustained decrease in cocaine-maintained responding in rhesus monkeys with 1-[2-[bis(4-fluorophenyl)methoxy]ethyl]4-(3-hydroxy-3-phenylpropyl)piperazinyl decanoate, a long-acting ester derivative of GBR 12909 [J].

Glowa, JR ;

Fantegrossi, WE ;

Lewis, DB ;

Matecka, D ;

Rice, KC ;

Rothman, RB .

JOURNAL OF MEDICINAL CHEMISTRY, 1996, 39 (24) :4689-4691

[9]

Hansch C., 1995, Exploring QSAR-Fundamentals and Applications in Chemistry and Biology

[10] Cocaine use and high-risk sexual behavior among STD clinic patients [J].

Hser, YI ;

Chou, CP ;

Hoffman, V ;

Anglin, MD .

SEXUALLY TRANSMITTED DISEASES, 1999, 26 (02) :82-86