Synthesis and evaluation of a series of homologues of lobelane at the vesicular monoamine transporter-2

Guangrong Zheng; Linda P. Dwoskin; Agripina G. Deaciuc; Peter A. Crooks

doi:10.1016/j.bmcl.2008.10.042

Synthesis and evaluation of a series of homologues of lobelane at the vesicular monoamine transporter-2

Guangrong Zheng, Linda P. Dwoskin, Agripina G. Deaciuc, Peter A. Crooks

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27 Scopus citations

Abstract

A series of lobelane homologues has been synthesized and evaluated for their [³H]DTBZ binding affinity at the vesicular monoamine transporter-2 (VMAT2). The structure-activity relationships (SAR) indicate that for retention of binding affinity at VMAT2, the lengths of the methylene linkers should be no shorter than one methylene unit at C-6 of the piperidine ring, and no shorter than two methylene units at C-2 of the piperidine ring. These results indicate that the intramolecular distances between the piperidine ring and two phenyl rings in lobelane analogues are an important criterion for retention of high affinity at VMAT2.

Original language	English
Pages (from-to)	6509-6512
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	18
Issue number	24
DOIs	https://doi.org/10.1016/j.bmcl.2008.10.042
State	Published - Dec 15 2008

Bibliographical note

Funding Information:
This research was supported by NIH Grant DA 13519.

Keywords

Lobelane
Structure-activity relationship
Vesicular monoamine transporter

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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10.1016/j.bmcl.2008.10.042

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title = "Synthesis and evaluation of a series of homologues of lobelane at the vesicular monoamine transporter-2",

abstract = "A series of lobelane homologues has been synthesized and evaluated for their [3H]DTBZ binding affinity at the vesicular monoamine transporter-2 (VMAT2). The structure-activity relationships (SAR) indicate that for retention of binding affinity at VMAT2, the lengths of the methylene linkers should be no shorter than one methylene unit at C-6 of the piperidine ring, and no shorter than two methylene units at C-2 of the piperidine ring. These results indicate that the intramolecular distances between the piperidine ring and two phenyl rings in lobelane analogues are an important criterion for retention of high affinity at VMAT2.",

keywords = "Lobelane, Structure-activity relationship, Vesicular monoamine transporter",

author = "Guangrong Zheng and Dwoskin, {Linda P.} and Deaciuc, {Agripina G.} and Crooks, {Peter A.}",

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doi = "10.1016/j.bmcl.2008.10.042",

language = "English",

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T1 - Synthesis and evaluation of a series of homologues of lobelane at the vesicular monoamine transporter-2

AU - Zheng, Guangrong

AU - Dwoskin, Linda P.

AU - Deaciuc, Agripina G.

AU - Crooks, Peter A.

N1 - Funding Information: This research was supported by NIH Grant DA 13519.

PY - 2008/12/15

Y1 - 2008/12/15

N2 - A series of lobelane homologues has been synthesized and evaluated for their [3H]DTBZ binding affinity at the vesicular monoamine transporter-2 (VMAT2). The structure-activity relationships (SAR) indicate that for retention of binding affinity at VMAT2, the lengths of the methylene linkers should be no shorter than one methylene unit at C-6 of the piperidine ring, and no shorter than two methylene units at C-2 of the piperidine ring. These results indicate that the intramolecular distances between the piperidine ring and two phenyl rings in lobelane analogues are an important criterion for retention of high affinity at VMAT2.

AB - A series of lobelane homologues has been synthesized and evaluated for their [3H]DTBZ binding affinity at the vesicular monoamine transporter-2 (VMAT2). The structure-activity relationships (SAR) indicate that for retention of binding affinity at VMAT2, the lengths of the methylene linkers should be no shorter than one methylene unit at C-6 of the piperidine ring, and no shorter than two methylene units at C-2 of the piperidine ring. These results indicate that the intramolecular distances between the piperidine ring and two phenyl rings in lobelane analogues are an important criterion for retention of high affinity at VMAT2.

KW - Lobelane

KW - Structure-activity relationship

KW - Vesicular monoamine transporter

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EP - 6512

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 24

ER -

Synthesis and evaluation of a series of homologues of lobelane at the vesicular monoamine transporter-2

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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