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

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

41 Citations (Scopus)

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 languageEnglish
Pages (from-to)1225-1228
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume15
Issue number4
DOIs
StatePublished - 15 Feb 2005

Fingerprint

Calcium-Sensing Receptors
Structure-Activity Relationship
Ether
Amines
Genes
N-(2-hydroxy-3-(2-cyano-3-chlorophenoxy)propyl)-1,1-dimethyl-2-(2-nephthyl)ethylamine
ethylamine

Keywords

  • Calcium-sensing receptor antagonist
  • Osteoporosis

Cite this

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.",
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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 › Research › peer-review

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

AU - Seethala, Ramakrishna

AU - Feyen, Jean H.M.

AU - Dickson, John K.

PY - 2005/2/15

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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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JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

SN - 0960-894X

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Yang W, Wang Y, Roberge JY, Ma Z, Liu Y, Lawrence RM et al. Discovery and structure-activity relationships of 2-benzylpyrrolidine- substituted aryloxypropanols as calcium-sensing receptor antagonists. Bioorganic and Medicinal Chemistry Letters. 2005 Feb 15;15(4):1225-1228. https://doi.org/10.1016/j.bmcl.2004.11.071

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