Synthesis of the calcilytic ligand NPS 2143

Beilstein Journal of Organic Chemistry

Hans Bräuner-Osborne¹  Daniel Sejer Pedersen¹  Thomas Cailly¹  Henrik Johansson¹  Alex Rojas Bie Thomsen¹ 

[1] Department of Drug Design and Pharmacology, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark;

关键词: epoxides;    GPCR;    NPS 2143;    nucleophilic aromatic substitution;    pyrylium chemistry;   

DOI  :  10.3762/bjoc.9.154

来源: DOAJ

【 摘 要 】

(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.

【 授权许可】

Unknown