Discovery and structure-activity relationships of 2-benzylpyrrolidine- substituted aryloxypropanols as calcium-sensing receptor antagonists

Wu Yang; Yufeng Wang; Jacques Y. Roberge; Zhengping Ma; Yalei Liu; R. Michael Lawrence; David P. Rotella; Ramakrishna Seethala; Jean H.M. Feyen; John K. Dickson

doi:10.1016/j.bmcl.2004.11.071

Discovery and structure-activity relationships of 2-benzylpyrrolidine- substituted aryloxypropanols as calcium-sensing receptor antagonists

Wu Yang, Yufeng Wang, Jacques Y. Roberge, Zhengping Ma, Yalei Liu, R. Michael Lawrence, David P. Rotella, Ramakrishna Seethala, Jean H.M. Feyen, John K. Dickson

Chemistry and Biochemistry

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45 Scopus citations

Abstract

A structure-activity relationship study of the amine portion of the calcilytic compound NPS-2143 resulted in the discovery of substituted 2-benzylpyrrolidines as replacements for the 1,1-dimethyl-2-naphthalen-2-yl- ethylamine. When compared to NPS-2143, a newly discovered compound, 3h, exhibited similar potency as a calcium-sensing receptor (CaR) antagonist and a superior human ether-a-go-go related gene (hERG) profile.

Original language	English
Pages (from-to)	1225-1228
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	15
Issue number	4
DOIs	https://doi.org/10.1016/j.bmcl.2004.11.071
State	Published - 15 Feb 2005

Keywords

Calcium-sensing receptor antagonist
Osteoporosis

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10.1016/j.bmcl.2004.11.071

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Yang, W., Wang, Y., Roberge, J. Y., Ma, Z., Liu, Y., Lawrence, R. M., Rotella, D. P., Seethala, R., Feyen, J. H. M., & Dickson, J. K. (2005). Discovery and structure-activity relationships of 2-benzylpyrrolidine- substituted aryloxypropanols as calcium-sensing receptor antagonists. Bioorganic and Medicinal Chemistry Letters, 15(4), 1225-1228. https://doi.org/10.1016/j.bmcl.2004.11.071

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abstract = "A structure-activity relationship study of the amine portion of the calcilytic compound NPS-2143 resulted in the discovery of substituted 2-benzylpyrrolidines as replacements for the 1,1-dimethyl-2-naphthalen-2-yl- ethylamine. When compared to NPS-2143, a newly discovered compound, 3h, exhibited similar potency as a calcium-sensing receptor (CaR) antagonist and a superior human ether-a-go-go related gene (hERG) profile.",

keywords = "Calcium-sensing receptor antagonist, Osteoporosis",

author = "Wu Yang and Yufeng Wang and Roberge, {Jacques Y.} and Zhengping Ma and Yalei Liu and Lawrence, {R. Michael} and Rotella, {David P.} and Ramakrishna Seethala and Feyen, {Jean H.M.} and Dickson, {John K.}",

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Yang, W, Wang, Y, Roberge, JY, Ma, Z, Liu, Y, Lawrence, RM, Rotella, DP, Seethala, R, Feyen, JHM & Dickson, JK 2005, 'Discovery and structure-activity relationships of 2-benzylpyrrolidine- substituted aryloxypropanols as calcium-sensing receptor antagonists', Bioorganic and Medicinal Chemistry Letters, vol. 15, no. 4, pp. 1225-1228. https://doi.org/10.1016/j.bmcl.2004.11.071

TY - JOUR

T1 - Discovery and structure-activity relationships of 2-benzylpyrrolidine- substituted aryloxypropanols as calcium-sensing receptor antagonists

AU - Yang, Wu

AU - Wang, Yufeng

AU - Roberge, Jacques Y.

AU - Ma, Zhengping

AU - Liu, Yalei

AU - Lawrence, R. Michael

AU - Rotella, David P.

AU - Seethala, Ramakrishna

AU - Feyen, Jean H.M.

AU - Dickson, John K.

PY - 2005/2/15

Y1 - 2005/2/15

N2 - A structure-activity relationship study of the amine portion of the calcilytic compound NPS-2143 resulted in the discovery of substituted 2-benzylpyrrolidines as replacements for the 1,1-dimethyl-2-naphthalen-2-yl- ethylamine. When compared to NPS-2143, a newly discovered compound, 3h, exhibited similar potency as a calcium-sensing receptor (CaR) antagonist and a superior human ether-a-go-go related gene (hERG) profile.

AB - A structure-activity relationship study of the amine portion of the calcilytic compound NPS-2143 resulted in the discovery of substituted 2-benzylpyrrolidines as replacements for the 1,1-dimethyl-2-naphthalen-2-yl- ethylamine. When compared to NPS-2143, a newly discovered compound, 3h, exhibited similar potency as a calcium-sensing receptor (CaR) antagonist and a superior human ether-a-go-go related gene (hERG) profile.

KW - Calcium-sensing receptor antagonist

KW - Osteoporosis

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SP - 1225

EP - 1228

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

SN - 0960-894X

IS - 4

ER -

Discovery and structure-activity relationships of 2-benzylpyrrolidine- substituted aryloxypropanols as calcium-sensing receptor antagonists

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Keywords

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