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 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 Rotella, Ramakrishna Seethala, Jean H.M. Feyen, John K. Dickson

Chemistry and Biochemistry

Research output: Contribution to journal › Article

43 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

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Keywords

Calcium-sensing receptor antagonist
Osteoporosis

Cite this

Yang, W., Wang, Y., Roberge, J. Y., Ma, Z., Liu, Y., Lawrence, R. M., Rotella, D., 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

Yang, Wu ; Wang, Yufeng ; Roberge, Jacques Y. ; Ma, Zhengping ; Liu, Yalei ; Lawrence, R. Michael ; Rotella, David ; Seethala, Ramakrishna ; Feyen, Jean H.M. ; Dickson, John K. / Discovery and structure-activity relationships of 2-benzylpyrrolidine- substituted aryloxypropanols as calcium-sensing receptor antagonists. In: Bioorganic and Medicinal Chemistry Letters. 2005 ; Vol. 15, No. 4. pp. 1225-1228.

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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 David Rotella 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, D, 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

Discovery and structure-activity relationships of 2-benzylpyrrolidine- substituted aryloxypropanols as calcium-sensing receptor antagonists. / Yang, Wu; Wang, Yufeng; Roberge, Jacques Y.; Ma, Zhengping; Liu, Yalei; Lawrence, R. Michael; Rotella, David; Seethala, Ramakrishna; Feyen, Jean H.M.; Dickson, John K.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 15, No. 4, 15.02.2005, p. 1225-1228.

Research output: Contribution to journal › Article

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AU - Liu, Yalei

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AU - Dickson, John K.

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10.1016/j.bmcl.2004.11.071

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