title: "Fit-for-purpose" development of analytical and (semi)preparative enantioselective high performance liquid and supercritical fluid chromatography for the access to a novel σ1 receptor agonist.
abstract: A rapid and straightforward screening protocol of chiral stationary phases (CSPs) in HPLC and SFC resulted in three different methods "fit-for-purpose", i.e. analysis and scale-up to semi-preparative enantioselective chromatography. The efficient use of these three methods allowed expedited preparation of an important drug discovery target, (R/S)-1, a potent new sigma 1 (σ1) receptor agonist. The approach taken resulted in significant savings of both time and labor for the isolation of enantiomers compared to the development of a stereo-selective synthesis. The enantiomers of 1 have been isolated allowing studies of their chirooptical properties and an in-deep comparative examination of the pharmacological profile for the individual enantiomers.
authors.affiliation: Department of Drug Sciences, Medicinal Chemistry and Pharmaceutical Technology Section, University of Pavia, Viale Taramelli 12, 27100 Pavia, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Rossi
authors.affiliation: NicOx Research Institute, Via Ariosto 21, 20091 Bresso (MI), Italy.
authors.forename: Annamaria
authors.initials: A
authors.lastname: Marra
authors.affiliation: Department of Drug Sciences, Medicinal Chemistry and Pharmaceutical Technology Section, University of Pavia, Viale Taramelli 12, 27100 Pavia, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Rui
authors.affiliation: NicOx Research Institute, Via Ariosto 21, 20091 Bresso (MI), Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Brambilla
authors.affiliation: Corden Pharma Switzerland LLC, Eichenweg 1, 4410 Liestal, Switzerland. Electronic address: Markus.Juza@cordenpharma.com.
authors.forename: Markus
authors.initials: M
authors.lastname: Juza
authors.affiliation: Department of Drug Sciences, Medicinal Chemistry and Pharmaceutical Technology Section, University of Pavia, Viale Taramelli 12, 27100 Pavia, Italy. Electronic address: simona.collina@unipv.it.
authors.forename: Simona
authors.initials: S
authors.lastname: Collina
mesh_terms: D000701:Analgesics, Opioid / Q000032:analysis* / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid / Q000379:methods / Q000639:trends; D025924:Chromatography, Supercritical Fluid / Q000379:methods* / Q000639:trends; D017480:Receptors, sigma / Q000819:agonists*; D013237:Stereoisomerism
chemical_list: D000701:Analgesics, Opioid; D017480:Receptors, sigma
keywords: Amylose and cellulose derived CSPs; Chiral resolution; Elution order; Enantioselective HPLC and SFC; Sigma 1 (σ(1)) receptor agonist