1. Synthesis of the calcilytic ligand NPS 2143
- Author
-
Hans Bräuner-Osborne, Alex R.B. Thomsen, Thomas Cailly, Henrik Johansson, and Daniel Sejer Pedersen
- Subjects
NPS-2143 ,pyrylium chemistry ,Allosteric modulator ,Chemistry ,Stereochemistry ,Organic Chemistry ,nucleophilic aromatic substitution ,Ligand (biochemistry) ,NPS 2143 ,Full Research Paper ,Chiral column chromatography ,lcsh:QD241-441 ,epoxides ,GPCR ,lcsh:Organic chemistry ,Nucleophilic aromatic substitution ,Calcilytic ,lcsh:Q ,Enantiomer ,Enantiomeric excess ,lcsh:Science - 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.
- Published
- 2013