title: Synthesis of a high specific activity methyl sulfone tritium isotopologue of fevipiprant (NVP-QAW039).
abstract: The synthesis of a triple tritiated isotopologue of the CRTh2 antagonist NVP-QAW039 (fevipiprant) with a specific activity >3 TBq/mmol is described. Key to the high specific activity is the methylation of a bench-stable dimeric disulfide precursor that is in situ reduced to the corresponding thiol monomer and methylated with [(3)H3]MeONos having per se a high specific activity. The high specific activity of the tritiated active pharmaceutical ingredient obtained by a build-up approach is discussed in the light of the specific activity usually to be expected if hydrogen tritium exchange methods were applied.
authors.affiliation: Novartis Pharma AG, Novartis Institutes for Biomedical Research, Forum 1 Novartis Campus, Basel, CH-4056, Switzerland.
authors.forename: Van T
authors.initials: VT
authors.lastname: Luu
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Goujon
authors.forename: Christian
authors.initials: C
authors.lastname: Meisterhans
authors.forename: Matthias
authors.initials: M
authors.lastname: Frommherz
authors.forename: Carsten
authors.initials: C
authors.lastname: Bauer
mesh_terms: D007210:Indoleacetic Acids / Q000138:chemical synthesis* / Q000494:pharmacology; D007212:Indolizines / Q000737:chemistry; D008745:Methylation; D011725:Pyridines / Q000138:chemical synthesis* / Q000494:pharmacology; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000494:pharmacology; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors; D013450:Sulfones / Q000737:chemistry; D014316:Tritium / Q000737:chemistry
chemical_list: D007210:Indoleacetic Acids; D007212:Indolizines; D011725:Pyridines; D019275:Radiopharmaceuticals; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; D013450:Sulfones; C588117:NVP-QAV680; D014316:Tritium; C000604875:fevipiprant; C036293:prostaglandin D2 receptor
keywords: 3-(2-methyl-7-aza-indolyl) acetic acid; CRTh2 receptor antagonists; NVP-QAV680; NVP-QAW039; [3H3]methyl nosylate; chemical cross-linking; fevipiprant; hydrogen isotope exchange; palladium catalysis; tritium