title: A novel five-lipoxygenase activity protein inhibitor labeled with carbon-14 and deuterium.
abstract: 2-[4-(3-{(1R)-1-[4-(2-Aminopyrimidin-5-yl)phenyl]-1-cyclopropylethyl}-1,2,4-oxadiazol-5-yl)-1H-pyrazol-1-yl]-N,N-dimethylacetamide (1), is a novel and selective five-lipoxygenase activity protein (FLAP) inhibitor with excellent pharmacokinetics properties. The availability of a key chiral intermediate allowed the synthesis of [(14) C]-(1) in six radiochemical steps and in 47% overall radiochemical yield with a specific activity of 51 mCi/mmol using carbon-14 zinc cyanide. 2-Chloro-N,N-dimethyl-(2)H6-acetamide was prepared and condensed with a penultimate intermediate to give [(2)H6]-(1) in very high yield and in more than 99% isotopic enrichment.
authors.affiliation: Chemical Development, Boehringer Ingelheim Pharmaceuticals, Inc., 900 Ridgebury Road, P.O. Box 368, Ridgefield, CT, 06877-0368, USA.
authors.forename: Bachir
authors.initials: B
authors.lastname: Latli
authors.affiliation: Chemical Development, Boehringer Ingelheim Pharmaceuticals, Inc., 900 Ridgebury Road, P.O. Box 368, Ridgefield, CT, 06877-0368, USA.
authors.forename: Matt
authors.initials: M
authors.lastname: Hrapchak
authors.affiliation: Chemical Development, Boehringer Ingelheim Pharmaceuticals, Inc., 900 Ridgebury Road, P.O. Box 368, Ridgefield, CT, 06877-0368, USA.
authors.forename: Joe J
authors.initials: JJ
authors.lastname: Gao
authors.affiliation: Chemical Development, Boehringer Ingelheim Pharmaceuticals, Inc., 900 Ridgebury Road, P.O. Box 368, Ridgefield, CT, 06877-0368, USA.
authors.forename: Carl A
authors.initials: CA
authors.lastname: Busacca
authors.affiliation: Chemical Development, Boehringer Ingelheim Pharmaceuticals, Inc., 900 Ridgebury Road, P.O. Box 368, Ridgefield, CT, 06877-0368, USA.
authors.forename: Chris H
authors.initials: CH
authors.lastname: Senanayake
mesh_terms: D002250:Carbon Radioisotopes / Q000737:chemistry*; D003903:Deuterium / Q000737:chemistry*; D007553:Isotope Labeling / Q000379:methods*; D016859:Lipoxygenase Inhibitors / Q000737:chemistry* / Q000302:isolation & purification; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000302:isolation & purification
chemical_list: D002250:Carbon Radioisotopes; D016859:Lipoxygenase Inhibitors; D019275:Radiopharmaceuticals; D003903:Deuterium
keywords: BI665915; FLAP; carbon-14; deuterium; radiosynthesis