Neuronal nicotinic acetylcholine receptor binding affinities of boron-containing nicotine analogues

Rui Xu; Linda P. Dwoskin; Vladimir P. Grinevich; Gabriela Deaciuc; Peter A. Crooks

doi:10.1016/S0960-894X(01)00193-7

Neuronal nicotinic acetylcholine receptor binding affinities of boron-containing nicotine analogues

Rui Xu, Linda P. Dwoskin, Vladimir P. Grinevich, Gabriela Deaciuc, Peter A. Crooks

Research output: Contribution to journal › Article › peer-review

27 Scopus citations

Abstract

A series of boron-containing nicotine (NIC) analogues 7-9 was synthesized and evaluated for binding to α4β2 and α7 nicotinic receptors. Compound ACME-B inhibited [³H]methyllycaconitine binding to rat brain membranes with a similar potency compared to NIC (K_i=2.4 and 0.77 μM, respectively), but was markedly less potent in inhibiting [³H]NIC binding when compared to NIC (K_i=0.60 μM and 1.0 nM, respectively). Thus, tethering a two-carbon bridge between the 2-pyridyl and 3′-pyrrolidino carbons of NIC or 7 affords analogues that bind to the α7 receptor in a manner similar to NIC, but with a dramatic loss of affinity for the α4β2 receptor.

Original language	English
Pages (from-to)	1245-1248
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	11
Issue number	9
DOIs	https://doi.org/10.1016/S0960-894X(01)00193-7
State	Published - May 7 2001

Bibliographical note

Funding Information:
This work was supported by grants from the National Institute on Drug Abuse (DA10394 and DA00399) and Layton Bioscience, Inc.

Funding

This work was supported by grants from the National Institute on Drug Abuse (DA10394 and DA00399) and Layton Bioscience, Inc.

Funders	Funder number
Layton Bioscience, Inc.
National Institute on Drug Abuse	R43DA010394, DA00399

ASJC Scopus subject areas

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

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title = "Neuronal nicotinic acetylcholine receptor binding affinities of boron-containing nicotine analogues",

abstract = "A series of boron-containing nicotine (NIC) analogues 7-9 was synthesized and evaluated for binding to α4β2 and α7 nicotinic receptors. Compound ACME-B inhibited [3H]methyllycaconitine binding to rat brain membranes with a similar potency compared to NIC (Ki=2.4 and 0.77 μM, respectively), but was markedly less potent in inhibiting [3H]NIC binding when compared to NIC (Ki=0.60 μM and 1.0 nM, respectively). Thus, tethering a two-carbon bridge between the 2-pyridyl and 3′-pyrrolidino carbons of NIC or 7 affords analogues that bind to the α7 receptor in a manner similar to NIC, but with a dramatic loss of affinity for the α4β2 receptor.",

author = "Rui Xu and Dwoskin, \{Linda P.\} and Grinevich, \{Vladimir P.\} and Gabriela Deaciuc and Crooks, \{Peter A.\}",

note = "Funding Information: This work was supported by grants from the National Institute on Drug Abuse (DA10394 and DA00399) and Layton Bioscience, Inc. ",

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AU - Xu, Rui

AU - Dwoskin, Linda P.

AU - Grinevich, Vladimir P.

AU - Deaciuc, Gabriela

AU - Crooks, Peter A.

N1 - Funding Information: This work was supported by grants from the National Institute on Drug Abuse (DA10394 and DA00399) and Layton Bioscience, Inc.

PY - 2001/5/7

Y1 - 2001/5/7

N2 - A series of boron-containing nicotine (NIC) analogues 7-9 was synthesized and evaluated for binding to α4β2 and α7 nicotinic receptors. Compound ACME-B inhibited [3H]methyllycaconitine binding to rat brain membranes with a similar potency compared to NIC (Ki=2.4 and 0.77 μM, respectively), but was markedly less potent in inhibiting [3H]NIC binding when compared to NIC (Ki=0.60 μM and 1.0 nM, respectively). Thus, tethering a two-carbon bridge between the 2-pyridyl and 3′-pyrrolidino carbons of NIC or 7 affords analogues that bind to the α7 receptor in a manner similar to NIC, but with a dramatic loss of affinity for the α4β2 receptor.

AB - A series of boron-containing nicotine (NIC) analogues 7-9 was synthesized and evaluated for binding to α4β2 and α7 nicotinic receptors. Compound ACME-B inhibited [3H]methyllycaconitine binding to rat brain membranes with a similar potency compared to NIC (Ki=2.4 and 0.77 μM, respectively), but was markedly less potent in inhibiting [3H]NIC binding when compared to NIC (Ki=0.60 μM and 1.0 nM, respectively). Thus, tethering a two-carbon bridge between the 2-pyridyl and 3′-pyrrolidino carbons of NIC or 7 affords analogues that bind to the α7 receptor in a manner similar to NIC, but with a dramatic loss of affinity for the α4β2 receptor.

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Neuronal nicotinic acetylcholine receptor binding affinities of boron-containing nicotine analogues

Abstract

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