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

26 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.

ASJC Scopus subject areas

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

Access to Document

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

Cite this

@article{e2687a73b12745cf88a0a2f544ca5f4c,

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. ",

year = "2001",

month = may,

day = "7",

doi = "10.1016/S0960-894X(01)00193-7",

language = "English",

volume = "11",

pages = "1245--1248",

number = "9",

}

TY - JOUR

T1 - Neuronal nicotinic acetylcholine receptor binding affinities of boron-containing nicotine analogues

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.

UR - http://www.scopus.com/inward/record.url?scp=0035821337&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035821337&partnerID=8YFLogxK

U2 - 10.1016/S0960-894X(01)00193-7

DO - 10.1016/S0960-894X(01)00193-7

M3 - Article

C2 - 11354387

AN - SCOPUS:0035821337

SN - 0960-894X

VL - 11

SP - 1245

EP - 1248

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 9

ER -

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

Abstract

Bibliographical note

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this