Discovery of non-peptide, small molecule antagonists of α9α10 nicotinic acetylcholine receptors as novel analgesics for the treatment of neuropathic and tonic inflammatory pain

Guangrong Zheng; Zhenfa Zhang; Cheryl Dowell; Elzbieta Wala; Linda P. Dwoskin; Joseph R. Holtman; J. Michael McIntosh; Peter A. Crooks

doi:10.1016/j.bmcl.2011.02.043

Discovery of non-peptide, small molecule antagonists of α9α10 nicotinic acetylcholine receptors as novel analgesics for the treatment of neuropathic and tonic inflammatory pain

Guangrong Zheng, Zhenfa Zhang, Cheryl Dowell, Elzbieta Wala, Linda P. Dwoskin, Joseph R. Holtman, J. Michael McIntosh, Peter A. Crooks

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

27 Scopus citations

Abstract

A series of azaaromatic quaternary ammonium analogs has been discovered as potent and selective α9α10 nicotinic acetylcholine receptor (nAChR) antagonists. The preliminary structure-activity relationships of these analogs suggest that increased rigidity in the linker units results in higher potency in inhibition of α9α10 nAChRs and greater selectivity over α7 nAChRs. These analogs represent a new class of analgesic for the treatment of neuropathic and tonic inflammatory pain.

Original language	English
Pages (from-to)	2476-2479
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	21
Issue number	8
DOIs	https://doi.org/10.1016/j.bmcl.2011.02.043
State	Published - Apr 15 2011

Bibliographical note

Funding Information:
This work was supported by NIH (Grant U19DA017548 to L.P.D. and P.A.C., MH53631 and GM48677 to J.M.M.) and a seed grant from the University of Utah Research Foundation to J.M.M.

Keywords

Analgesic
Pain
SAR
α9α10 nAChR

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.2011.02.043

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Zheng, G., Zhang, Z., Dowell, C., Wala, E., Dwoskin, L. P., Holtman, J. R., McIntosh, J. M., & Crooks, P. A. (2011). Discovery of non-peptide, small molecule antagonists of α9α10 nicotinic acetylcholine receptors as novel analgesics for the treatment of neuropathic and tonic inflammatory pain. Bioorganic and Medicinal Chemistry Letters, 21(8), 2476-2479. https://doi.org/10.1016/j.bmcl.2011.02.043

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abstract = "A series of azaaromatic quaternary ammonium analogs has been discovered as potent and selective α9α10 nicotinic acetylcholine receptor (nAChR) antagonists. The preliminary structure-activity relationships of these analogs suggest that increased rigidity in the linker units results in higher potency in inhibition of α9α10 nAChRs and greater selectivity over α7 nAChRs. These analogs represent a new class of analgesic for the treatment of neuropathic and tonic inflammatory pain.",

keywords = "Analgesic, Pain, SAR, α9α10 nAChR",

author = "Guangrong Zheng and Zhenfa Zhang and Cheryl Dowell and Elzbieta Wala and Dwoskin, {Linda P.} and Holtman, {Joseph R.} and McIntosh, {J. Michael} and Crooks, {Peter A.}",

note = "Funding Information: This work was supported by NIH (Grant U19DA017548 to L.P.D. and P.A.C., MH53631 and GM48677 to J.M.M.) and a seed grant from the University of Utah Research Foundation to J.M.M. ",

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Zheng, G, Zhang, Z, Dowell, C, Wala, E, Dwoskin, LP, Holtman, JR, McIntosh, JM & Crooks, PA 2011, 'Discovery of non-peptide, small molecule antagonists of α9α10 nicotinic acetylcholine receptors as novel analgesics for the treatment of neuropathic and tonic inflammatory pain', Bioorganic and Medicinal Chemistry Letters, vol. 21, no. 8, pp. 2476-2479. https://doi.org/10.1016/j.bmcl.2011.02.043

Discovery of non-peptide, small molecule antagonists of α9α10 nicotinic acetylcholine receptors as novel analgesics for the treatment of neuropathic and tonic inflammatory pain. / Zheng, Guangrong; Zhang, Zhenfa; Dowell, Cheryl et al.
In: Bioorganic and Medicinal Chemistry Letters, Vol. 21, No. 8, 15.04.2011, p. 2476-2479.

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

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AU - Zheng, Guangrong

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AU - Dowell, Cheryl

AU - Wala, Elzbieta

AU - Dwoskin, Linda P.

AU - Holtman, Joseph R.

AU - McIntosh, J. Michael

AU - Crooks, Peter A.

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KW - Pain

KW - SAR

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Discovery of non-peptide, small molecule antagonists of α9α10 nicotinic acetylcholine receptors as novel analgesics for the treatment of neuropathic and tonic inflammatory pain

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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