Discovery of biphenyl piperazines as novel and long acting muscarinic acetylcholine receptor antagonists

Jian Jin; Brian Budzik; Yonghui Wang; Dongchuan Shi; Feng Wang; Haibo Xie; Zehong Wan; Chongye Zhu; James J. Foley; Edward F. Webb; Manuela Berlanga; Miriam Burman; Henry M. Sarau; Dwight M. Morrow; Michael L. Moore; Ralph A. Rivero; Michael Palovich; Michael Salmon; Kristen E. Belmonte; Dramane I. Lainé

doi:10.1021/jm800935u

Discovery of biphenyl piperazines as novel and long acting muscarinic acetylcholine receptor antagonists

Jian Jin, Brian Budzik, Yonghui Wang, Dongchuan Shi, Feng Wang, Haibo Xie, Zehong Wan, Chongye Zhu, James J. Foley, Edward F. Webb, Manuela Berlanga, Miriam Burman, Henry M. Sarau, Dwight M. Morrow, Michael L. Moore, Ralph A. Rivero, Michael Palovich, Michael Salmon, Kristen E. Belmonte, Dramane I. Lainé

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

16 Scopus citations

Abstract

A series of novel biphenyl piperazines was discovered as highly potent muscarinic acetylcholine receptor antagonists via high throughput screening and subsequent optimization. Compound 5c with respective 500- and 20-fold subtype selectivity for M₃ over M₂ and M₁ exhibited excellent inhibitory activity and long duration of action in a bronchoconstriction in vivo model in mice via intranasal administration. The novel inhaled mAChR antagonists are potentially useful therapeutic agents for the treatment of chronic obstructive pulmonary disease.

Original language	English
Pages (from-to)	5915-5918
Number of pages	4
Journal	Journal of Medicinal Chemistry
Volume	51
Issue number	19
DOIs	https://doi.org/10.1021/jm800935u
State	Published - 9 Oct 2008
Externally published	Yes

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Jin, J., Budzik, B., Wang, Y., Shi, D., Wang, F., Xie, H., Wan, Z., Zhu, C., Foley, J. J., Webb, E. F., Berlanga, M., Burman, M., Sarau, H. M., Morrow, D. M., Moore, M. L., Rivero, R. A., Palovich, M., Salmon, M., Belmonte, K. E., & Lainé, D. I. (2008). Discovery of biphenyl piperazines as novel and long acting muscarinic acetylcholine receptor antagonists. Journal of Medicinal Chemistry, 51(19), 5915-5918. https://doi.org/10.1021/jm800935u

@article{90fe7b64a19541d0af2735fe63f8a1d9,

title = "Discovery of biphenyl piperazines as novel and long acting muscarinic acetylcholine receptor antagonists",

abstract = "A series of novel biphenyl piperazines was discovered as highly potent muscarinic acetylcholine receptor antagonists via high throughput screening and subsequent optimization. Compound 5c with respective 500- and 20-fold subtype selectivity for M3 over M2 and M1 exhibited excellent inhibitory activity and long duration of action in a bronchoconstriction in vivo model in mice via intranasal administration. The novel inhaled mAChR antagonists are potentially useful therapeutic agents for the treatment of chronic obstructive pulmonary disease.",

author = "Jian Jin and 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 Webb, {Edward F.} and Manuela Berlanga and Miriam Burman 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 Lain{\'e}, {Dramane I.}",

year = "2008",

month = oct,

day = "9",

doi = "10.1021/jm800935u",

language = "English",

volume = "51",

pages = "5915--5918",

journal = "Journal of Medicinal Chemistry",

issn = "0022-2623",

publisher = "American Chemical Society",

number = "19",

}

Jin, J, Budzik, B, Wang, Y, Shi, D, Wang, F, Xie, H, Wan, Z, Zhu, C, Foley, JJ, Webb, EF, Berlanga, M, Burman, M, Sarau, HM, Morrow, DM, Moore, ML, Rivero, RA, Palovich, M, Salmon, M, Belmonte, KE & Lainé, DI 2008, 'Discovery of biphenyl piperazines as novel and long acting muscarinic acetylcholine receptor antagonists', Journal of Medicinal Chemistry, vol. 51, no. 19, pp. 5915-5918. https://doi.org/10.1021/jm800935u

TY - JOUR

T1 - Discovery of biphenyl piperazines as novel and long acting muscarinic acetylcholine receptor antagonists

AU - Jin, Jian

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 - Webb, Edward F.

AU - Berlanga, Manuela

AU - Burman, Miriam

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 - Lainé, Dramane I.

PY - 2008/10/9

Y1 - 2008/10/9

N2 - A series of novel biphenyl piperazines was discovered as highly potent muscarinic acetylcholine receptor antagonists via high throughput screening and subsequent optimization. Compound 5c with respective 500- and 20-fold subtype selectivity for M3 over M2 and M1 exhibited excellent inhibitory activity and long duration of action in a bronchoconstriction in vivo model in mice via intranasal administration. The novel inhaled mAChR antagonists are potentially useful therapeutic agents for the treatment of chronic obstructive pulmonary disease.

AB - A series of novel biphenyl piperazines was discovered as highly potent muscarinic acetylcholine receptor antagonists via high throughput screening and subsequent optimization. Compound 5c with respective 500- and 20-fold subtype selectivity for M3 over M2 and M1 exhibited excellent inhibitory activity and long duration of action in a bronchoconstriction in vivo model in mice via intranasal administration. The novel inhaled mAChR antagonists are potentially useful therapeutic agents for the treatment of chronic obstructive pulmonary disease.

UR - http://www.scopus.com/inward/record.url?scp=53549091063&partnerID=8YFLogxK

U2 - 10.1021/jm800935u

DO - 10.1021/jm800935u

M3 - Article

C2 - 18798607

AN - SCOPUS:53549091063

SN - 0022-2623

VL - 51

SP - 5915

EP - 5918

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

IS - 19

ER -

Discovery of biphenyl piperazines as novel and long acting muscarinic acetylcholine receptor antagonists

Abstract

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