Tyrosine urea muscarinic acetylcholine receptor antagonists: Achiral quaternary ammonium groups

Qi Jin; Roderick S. Davis; Ann M. Bullion; Jian Jin; Yonghui Wang; Katherine L. Widdowson; Michael R. Palovich; James J. Foley; Dulcie B. Schmidt; Peter T. Buckley; Edward F. Webb; Michael Salmon; Kristen E. Belmonte; Henry M. Sarau; Jakob Busch-Petersen

doi:10.1016/j.bmcl.2012.09.085

Tyrosine urea muscarinic acetylcholine receptor antagonists: Achiral quaternary ammonium groups

Qi Jin
, Roderick S. Davis
, Ann M. Bullion
, Jian Jin
, Yonghui Wang
, Katherine L. Widdowson
, Michael R. Palovich
, James J. Foley
, Dulcie B. Schmidt
, Peter T. Buckley
, Edward F. Webb
, Michael Salmon
, Kristen E. Belmonte
, Henry M. Sarau
, Jakob Busch-Petersen

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

3 Scopus citations

Abstract

Tyrosine ureas had been identified as potent muscarinic receptor antagonists with promising in vivo activity. Controlling the stereochemistry of the chiral quaternary ammonium center had proved to be a serious issue for this series, however. Herein we describe the preparation and SAR of tyrosine urea antagonists containing achiral quaternary ammonium centers. The most successful such moiety was the 2-methylimidazo[2,1-b][1,3]thiazol-7-ium group which yielded highly potent antagonists with long duration of action in an inhaled animal model of bronchoconstriction.

Original language	English
Pages (from-to)	7087-7091
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	22
Issue number	23
DOIs	https://doi.org/10.1016/j.bmcl.2012.09.085
State	Published - 1 Dec 2012
Externally published	Yes

Keywords

Airway disease
Inhaled
Muscarinic antagonists
Quaternary ammonium salts
Solid phase synthesis

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10.1016/j.bmcl.2012.09.085

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Jin, Q., Davis, R. S., Bullion, A. M., Jin, J., Wang, Y., Widdowson, K. L., Palovich, M. R., Foley, J. J., Schmidt, D. B., Buckley, P. T., Webb, E. F., Salmon, M., Belmonte, K. E., Sarau, H. M., & Busch-Petersen, J. (2012). Tyrosine urea muscarinic acetylcholine receptor antagonists: Achiral quaternary ammonium groups. Bioorganic and Medicinal Chemistry Letters, 22(23), 7087-7091. https://doi.org/10.1016/j.bmcl.2012.09.085

@article{2d991eabf9274668bb7916600cd0e514,

title = "Tyrosine urea muscarinic acetylcholine receptor antagonists: Achiral quaternary ammonium groups",

abstract = "Tyrosine ureas had been identified as potent muscarinic receptor antagonists with promising in vivo activity. Controlling the stereochemistry of the chiral quaternary ammonium center had proved to be a serious issue for this series, however. Herein we describe the preparation and SAR of tyrosine urea antagonists containing achiral quaternary ammonium centers. The most successful such moiety was the 2-methylimidazo[2,1-b][1,3]thiazol-7-ium group which yielded highly potent antagonists with long duration of action in an inhaled animal model of bronchoconstriction.",

keywords = "Airway disease, Inhaled, Muscarinic antagonists, Quaternary ammonium salts, Solid phase synthesis",

author = "Qi Jin and Davis, \{Roderick S.\} and Bullion, \{Ann M.\} and Jian Jin and Yonghui Wang and Widdowson, \{Katherine L.\} and Palovich, \{Michael R.\} and Foley, \{James J.\} and Schmidt, \{Dulcie B.\} and Buckley, \{Peter T.\} and Webb, \{Edward F.\} and Michael Salmon and Belmonte, \{Kristen E.\} and Sarau, \{Henry M.\} and Jakob Busch-Petersen",

year = "2012",

month = dec,

day = "1",

doi = "10.1016/j.bmcl.2012.09.085",

language = "English",

volume = "22",

pages = "7087--7091",

journal = "Bioorganic and Medicinal Chemistry Letters",

issn = "0960-894X",

publisher = "Elsevier Ltd.",

number = "23",

}

Jin, Q, Davis, RS, Bullion, AM, Jin, J, Wang, Y, Widdowson, KL, Palovich, MR, Foley, JJ, Schmidt, DB, Buckley, PT, Webb, EF, Salmon, M, Belmonte, KE, Sarau, HM & Busch-Petersen, J 2012, 'Tyrosine urea muscarinic acetylcholine receptor antagonists: Achiral quaternary ammonium groups', Bioorganic and Medicinal Chemistry Letters, vol. 22, no. 23, pp. 7087-7091. https://doi.org/10.1016/j.bmcl.2012.09.085

TY - JOUR

T1 - Tyrosine urea muscarinic acetylcholine receptor antagonists

T2 - Achiral quaternary ammonium groups

AU - Jin, Qi

AU - Davis, Roderick S.

AU - Bullion, Ann M.

AU - Jin, Jian

AU - Wang, Yonghui

AU - Widdowson, Katherine L.

AU - Palovich, Michael R.

AU - Foley, James J.

AU - Schmidt, Dulcie B.

AU - Buckley, Peter T.

AU - Webb, Edward F.

AU - Salmon, Michael

AU - Belmonte, Kristen E.

AU - Sarau, Henry M.

AU - Busch-Petersen, Jakob

PY - 2012/12/1

Y1 - 2012/12/1

N2 - Tyrosine ureas had been identified as potent muscarinic receptor antagonists with promising in vivo activity. Controlling the stereochemistry of the chiral quaternary ammonium center had proved to be a serious issue for this series, however. Herein we describe the preparation and SAR of tyrosine urea antagonists containing achiral quaternary ammonium centers. The most successful such moiety was the 2-methylimidazo[2,1-b][1,3]thiazol-7-ium group which yielded highly potent antagonists with long duration of action in an inhaled animal model of bronchoconstriction.

AB - Tyrosine ureas had been identified as potent muscarinic receptor antagonists with promising in vivo activity. Controlling the stereochemistry of the chiral quaternary ammonium center had proved to be a serious issue for this series, however. Herein we describe the preparation and SAR of tyrosine urea antagonists containing achiral quaternary ammonium centers. The most successful such moiety was the 2-methylimidazo[2,1-b][1,3]thiazol-7-ium group which yielded highly potent antagonists with long duration of action in an inhaled animal model of bronchoconstriction.

KW - Airway disease

KW - Inhaled

KW - Muscarinic antagonists

KW - Quaternary ammonium salts

KW - Solid phase synthesis

UR - https://www.scopus.com/pages/publications/84869087778

U2 - 10.1016/j.bmcl.2012.09.085

DO - 10.1016/j.bmcl.2012.09.085

M3 - Article

C2 - 23099092

AN - SCOPUS:84869087778

SN - 0960-894X

VL - 22

SP - 7087

EP - 7091

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 23

ER -

Tyrosine urea muscarinic acetylcholine receptor antagonists: Achiral quaternary ammonium groups

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Keywords

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