title: Synthesis of 2,6-difluoro-N-(3-[11C]methoxy-1H-pyrazolo[3,4-b]pyridine-5-yl)-3-(propylsulfonamidio)benzamide as a new potential PET agent for imaging of B-Raf(V600E) in cancers.
abstract: The authentic standard 2,6-difluoro-N-(3-methoxy-1H-pyrazolo[3,4-b]pyridine-5-yl)-3-(propylsulfonamidio)benzamide was synthesized from 2,6-difluorobenzoic acid and 3-amino-5-hydroxypyrazole in 9 steps with 1% overall chemical yield. Direct desmethylation of the reference standard with TMSCl/NaI gave the precursor 2,6-difluoro-N-(3-hydroxy-1H-pyrazolo[3,4-b]pyridine-5-yl)-3-(propylsulfonamidio)benzamide for radiolabeling in 70% yield. The target tracer 2,6-difluoro-N-(3-[(11)C]methoxy-1H-pyrazolo[3,4-b]pyridine-5-yl)-3-(propylsulfonamidio)benzamide was prepared from the precursor with [(11)C]CH(3)OTf through O-[(11)C]methylation and isolated by HPLC combined with SPE in 40-50% decay corrected radiochemical yields with 370-740 GBq/μmol specific activity at end of bombardment (EOB).
authors.affiliation: Department of Radiology and Imaging Sciences, Indiana University School of Medicine, 1345 West 16th Street, Room 202, Indianapolis, IN 46202, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.forename: Mingzhang
authors.initials: M
authors.lastname: Gao
authors.forename: Kathy D
authors.initials: KD
authors.lastname: Miller
authors.forename: Qi-Huang
authors.initials: QH
authors.lastname: Zheng
mesh_terms: D001549:Benzamides / Q000138:chemical synthesis* / Q000737:chemistry; D006801:Humans; D009369:Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism; D049268:Positron-Emission Tomography / Q000379:methods*; D048493:Proto-Oncogene Proteins B-raf / Q000032:analysis; D011720:Pyrazoles / Q000737:chemistry / Q000494:pharmacology; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry; D019275:Radiopharmaceuticals / Q000138:chemical synthesis*
chemical_list: D001549:Benzamides; D011720:Pyrazoles; D011725:Pyridines; D019275:Radiopharmaceuticals; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf