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

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

49 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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doi = "10.1016/j.bmcl.2004.11.071",

language = "English",

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journal = "Bioorganic and Medicinal Chemistry Letters",

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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

UR - https://www.scopus.com/pages/publications/20144387408

U2 - 10.1016/j.bmcl.2004.11.071

DO - 10.1016/j.bmcl.2004.11.071

M3 - Article

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AN - SCOPUS:20144387408

SN - 0960-894X

VL - 15

SP - 1225

EP - 1228

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 4

ER -

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

Abstract

Keywords

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