Synthesis of 14 C- and 2 H-labelled CHF6001: A new potent PDE4 inhibitor

E Fontana; V Cenacchi; F Pivetti; A Pignatti; T Pazzi; L Bondanza; M Pazzi

doi:10.1002/jlcr.3537

Synthesis of ¹⁴ C- and ² H-labelled CHF6001: A new potent PDE4 inhibitor

J Labelled Comp Radiopharm. 2017 Oct;60(12):577-585. doi: 10.1002/jlcr.3537. Epub 2017 Sep 18.

Authors

E Fontana¹, V Cenacchi², F Pivetti³, A Pignatti¹, T Pazzi⁴, L Bondanza⁴, M Pazzi⁴

Affiliations

¹ Isotope Chemistry, Accelera S.r.l., Nerviano (MI), Italy.
² Pharmacokinetics Biochemistry and Metabolism, Corporate Pre-Clinical R&D Chiesi Farmaceutici SpA, Parma, Italy.
³ Chemical Process Development, Chiesi Farmaceutici SpA, Parma, Italy.
⁴ Chimete S.r.l., Tortona (Al), Italy.

PMID: 28763109
DOI: 10.1002/jlcr.3537

Abstract

An 8-step preparation of ¹⁴ C-labelled CHF6001, a potent phosphodiesterase 4 inhibitor in the treatment of respiratory diseases, is described. An overall yield of approximately 9% was obtained starting from copper[¹⁴ C]cyanide. The synthesis of a stable labelled version of CHF6001 is also reported using the commercially available trideuterated bromomethylcyclopropane as starting material.

Keywords: CHF6001; PDE4 inhibitor; carbon-14; deuterium; internal standard.

MeSH terms

Carbon Radioisotopes / chemistry*
Chemistry Techniques, Synthetic
Cyclic Nucleotide Phosphodiesterases, Type 4 / metabolism*
Deuterium / chemistry*
Isotope Labeling
Phosphodiesterase 4 Inhibitors / chemical synthesis*
Phosphodiesterase 4 Inhibitors / chemistry*
Phosphodiesterase 4 Inhibitors / pharmacology
Sulfonamides / chemical synthesis*
Sulfonamides / chemistry*
Sulfonamides / pharmacology
para-Aminobenzoates / chemical synthesis*
para-Aminobenzoates / chemistry*
para-Aminobenzoates / pharmacology

Substances

tanimilast
Carbon Radioisotopes
Phosphodiesterase 4 Inhibitors
Sulfonamides
para-Aminobenzoates
Carbon-14
Deuterium
Cyclic Nucleotide Phosphodiesterases, Type 4