Synthesis of the calcilytic ligand NPS 2143

Henrik Johansson; Thomas Cailly; Alex Rojas Bie Thomsen; Hans Bräuner-Osborne; Daniel Sejer Pedersen

doi:10.3762/bjoc.9.154

Synthesis of the calcilytic ligand NPS 2143

Henrik Johansson, Thomas Cailly, Alex Rojas Bie Thomsen, Hans Bräuner-Osborne, Daniel Sejer Pedersen

Molecular Pathobiology

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

Abstract

(R)-3 (NPS 2143) is a negative allosteric modulator of the human calcium-sensing receptor (CaSR) and as such represents an important pharmacological tool compound for studying the CaSR. Herein, we disclose for the first time a complete experimental description, detailed characterisation and assessment of enantiomeric purity for (R)-3. An efficient, reproducible and scalable synthesis of (R)-3 that requires a minimum of chromatographic purification steps is presented. (R)-3 was obtained in excellent optical purity (er > 99:1) as demonstrated by chiral HPLC and the pharmacological profile for (R)-3 is in full accordance with that reported in the literature.

Original language	English (US)
Pages (from-to)	1383-1387
Number of pages	5
Journal	Beilstein Journal of Organic Chemistry
Volume	9
DOIs	https://doi.org/10.3762/bjoc.9.154
State	Published - Jul 9 2013

Keywords

Epoxides
GPCR
NPS 2143
Nucleophilic aromatic substitution
Pyrylium chemistry

ASJC Scopus subject areas

Organic Chemistry

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10.3762/bjoc.9.154

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abstract = "(R)-3 (NPS 2143) is a negative allosteric modulator of the human calcium-sensing receptor (CaSR) and as such represents an important pharmacological tool compound for studying the CaSR. Herein, we disclose for the first time a complete experimental description, detailed characterisation and assessment of enantiomeric purity for (R)-3. An efficient, reproducible and scalable synthesis of (R)-3 that requires a minimum of chromatographic purification steps is presented. (R)-3 was obtained in excellent optical purity (er > 99:1) as demonstrated by chiral HPLC and the pharmacological profile for (R)-3 is in full accordance with that reported in the literature.",

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AU - Johansson, Henrik

AU - Cailly, Thomas

AU - Thomsen, Alex Rojas Bie

AU - Bräuner-Osborne, Hans

AU - Pedersen, Daniel Sejer

PY - 2013/7/9

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AB - (R)-3 (NPS 2143) is a negative allosteric modulator of the human calcium-sensing receptor (CaSR) and as such represents an important pharmacological tool compound for studying the CaSR. Herein, we disclose for the first time a complete experimental description, detailed characterisation and assessment of enantiomeric purity for (R)-3. An efficient, reproducible and scalable synthesis of (R)-3 that requires a minimum of chromatographic purification steps is presented. (R)-3 was obtained in excellent optical purity (er > 99:1) as demonstrated by chiral HPLC and the pharmacological profile for (R)-3 is in full accordance with that reported in the literature.

KW - Epoxides

KW - GPCR

KW - NPS 2143

KW - Nucleophilic aromatic substitution

KW - Pyrylium chemistry

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Synthesis of the calcilytic ligand NPS 2143

Abstract

Keywords

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