M3 muscarinic acetylcholine receptor antagonists: SAR and optimization of bi-aryl amines

Brian Budzik; Yonghui Wang; Dongchuan Shi; Feng Wang; Haibo Xie; Zehong Wan; Chongye Zhu; James J. Foley; Parvathi Nuthulaganti; Lorena A. Kallal; Henry M. Sarau; Dwight M. Morrow; Michael L. Moore; Ralph A. Rivero; Michael Palovich; Michael Salmon; Kristen E. Belmonte; Dramane I. Laine; Jian Jin

doi:10.1016/j.bmcl.2009.01.098

M₃ muscarinic acetylcholine receptor antagonists: SAR and optimization of bi-aryl amines

Brian Budzik, Yonghui Wang, Dongchuan Shi, Feng Wang, Haibo Xie, Zehong Wan, Chongye Zhu, James J. Foley, Parvathi Nuthulaganti, Lorena A. Kallal, Henry M. Sarau, Dwight M. Morrow, Michael L. Moore, Ralph A. Rivero, Michael Palovich, Michael Salmon, Kristen E. Belmonte, Dramane I. Laine, Jian Jin

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

4 Scopus citations

Abstract

Exploration of multiple regions of a bi-aryl amine template led to the identification of highly potent M₃ muscarinic acetylcholine receptor antagonists such as 14 (pA₂ = 11.0) possessing good sub-type selectivity for M₃ over M₂. The structure-activity relationships (SAR) and optimization of the bi-aryl amine series are described.

Original language	English
Pages (from-to)	1686-1690
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	19
Issue number	6
DOIs	https://doi.org/10.1016/j.bmcl.2009.01.098
State	Published - 15 Mar 2009
Externally published	Yes

Keywords

Antagonists
Asthma
Bi-aryl amines
COPD
M mAChR
Muscarinic acetylcholine receptor
SAR
Sub-type selectivity

Access to Document

10.1016/j.bmcl.2009.01.098

Cite this

Budzik, B., Wang, Y., Shi, D., Wang, F., Xie, H., Wan, Z., Zhu, C., Foley, J. J., Nuthulaganti, P., Kallal, L. A., Sarau, H. M., Morrow, D. M., Moore, M. L., Rivero, R. A., Palovich, M., Salmon, M., Belmonte, K. E., Laine, D. I., & Jin, J. (2009). M₃ muscarinic acetylcholine receptor antagonists: SAR and optimization of bi-aryl amines. Bioorganic and Medicinal Chemistry Letters, 19(6), 1686-1690. https://doi.org/10.1016/j.bmcl.2009.01.098

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title = "M3 muscarinic acetylcholine receptor antagonists: SAR and optimization of bi-aryl amines",

abstract = "Exploration of multiple regions of a bi-aryl amine template led to the identification of highly potent M3 muscarinic acetylcholine receptor antagonists such as 14 (pA2 = 11.0) possessing good sub-type selectivity for M3 over M2. The structure-activity relationships (SAR) and optimization of the bi-aryl amine series are described.",

keywords = "Antagonists, Asthma, Bi-aryl amines, COPD, M mAChR, Muscarinic acetylcholine receptor, SAR, Sub-type selectivity",

author = "Brian Budzik and Yonghui Wang and Dongchuan Shi and Feng Wang and Haibo Xie and Zehong Wan and Chongye Zhu and Foley, {James J.} and Parvathi Nuthulaganti and Kallal, {Lorena A.} and Sarau, {Henry M.} and Morrow, {Dwight M.} and Moore, {Michael L.} and Rivero, {Ralph A.} and Michael Palovich and Michael Salmon and Belmonte, {Kristen E.} and Laine, {Dramane I.} and Jian Jin",

year = "2009",

month = mar,

day = "15",

doi = "10.1016/j.bmcl.2009.01.098",

language = "English",

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Budzik, B, Wang, Y, Shi, D, Wang, F, Xie, H, Wan, Z, Zhu, C, Foley, JJ, Nuthulaganti, P, Kallal, LA, Sarau, HM, Morrow, DM, Moore, ML, Rivero, RA, Palovich, M, Salmon, M, Belmonte, KE, Laine, DI & Jin, J 2009, 'M₃ muscarinic acetylcholine receptor antagonists: SAR and optimization of bi-aryl amines', Bioorganic and Medicinal Chemistry Letters, vol. 19, no. 6, pp. 1686-1690. https://doi.org/10.1016/j.bmcl.2009.01.098

TY - JOUR

T1 - M3 muscarinic acetylcholine receptor antagonists

T2 - SAR and optimization of bi-aryl amines

AU - Budzik, Brian

AU - Wang, Yonghui

AU - Shi, Dongchuan

AU - Wang, Feng

AU - Xie, Haibo

AU - Wan, Zehong

AU - Zhu, Chongye

AU - Foley, James J.

AU - Nuthulaganti, Parvathi

AU - Kallal, Lorena A.

AU - Sarau, Henry M.

AU - Morrow, Dwight M.

AU - Moore, Michael L.

AU - Rivero, Ralph A.

AU - Palovich, Michael

AU - Salmon, Michael

AU - Belmonte, Kristen E.

AU - Laine, Dramane I.

AU - Jin, Jian

PY - 2009/3/15

Y1 - 2009/3/15

N2 - Exploration of multiple regions of a bi-aryl amine template led to the identification of highly potent M3 muscarinic acetylcholine receptor antagonists such as 14 (pA2 = 11.0) possessing good sub-type selectivity for M3 over M2. The structure-activity relationships (SAR) and optimization of the bi-aryl amine series are described.

AB - Exploration of multiple regions of a bi-aryl amine template led to the identification of highly potent M3 muscarinic acetylcholine receptor antagonists such as 14 (pA2 = 11.0) possessing good sub-type selectivity for M3 over M2. The structure-activity relationships (SAR) and optimization of the bi-aryl amine series are described.

KW - Antagonists

KW - Asthma

KW - Bi-aryl amines

KW - COPD

KW - M mAChR

KW - Muscarinic acetylcholine receptor

KW - SAR

KW - Sub-type selectivity

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JO - Bioorganic and Medicinal Chemistry Letters

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