title: Synthesis of carbon-11-labeled 4-(phenylamino)-pyrrolo[2,1-f][1,2,4]triazine derivatives as new potential PET tracers for imaging of p38α mitogen-activated protein kinase.
abstract: The reference standards methyl 4-(2-methyl-5-(methoxycarbamoyl)phenylamino)-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylate (10a), methyl 4-(2-methyl-5-(ethoxycarbamoyl)phenylamino)-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylate (10b) and corresponding precursors 4-(2-methyl-5-(methoxycarbamoyl)phenylamino)-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylic acid (11a), methyl 4-(2-methyl-5-(ethoxycarbamoyl)phenylamino)-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylic acid (11b) were synthesized from methyl crotonate and 3-amino-4-methylbenzoic acid in multiple steps with moderate to excellent yields. The target tracer [(11)C]methyl 4-(2-methyl-5-(methoxycarbamoyl)phenylamino)-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylate ([(11)C]10a) and [(11)C]methyl 4-(2-methyl-5-(ethoxycarbamoyl)phenylamino)-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylate ([(11)C]10b) were prepared from their corresponding precursors with [(11)C]CH3OTf under basic condition through O-[(11)C]methylation and isolated by a simplified solid-phase extraction (SPE) method in 50-60% radiochemical yields at end of bombardment (EOB) with 185-555 GBq/μmol specific activity at end of synthesis (EOS).
authors: Department of Radiology and Imaging Sciences, Indiana University School of Medicine, 1345 West 16th Street, Room 202, Indianapolis, IN 46202, USA.
authors: Min
authors: M
authors: Wang
authors: Department of Radiology and Imaging Sciences, Indiana University School of Medicine, 1345 West 16th Street, Room 202, Indianapolis, IN 46202, USA.
authors: Mingzhang
authors: M
authors: Gao
authors: Department of Radiology and Imaging Sciences, Indiana University School of Medicine, 1345 West 16th Street, Room 202, Indianapolis, IN 46202, USA. Electronic address: qzheng@iupui.edu.
authors: Qi-Huang
authors: QH
authors: Zheng
mesh_terms: D002250:Carbon Radioisotopes; D003952:Diagnostic Imaging; D004305:Dose-Response Relationship, Drug; D006801:Humans; D048308:Mitogen-Activated Protein Kinase 14 / Q000032:analysis* / Q000037:antagonists & inhibitors / Q000378:metabolism; D015394:Molecular Structure; D049268:Positron-Emission Tomography; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000494:pharmacology; D011758:Pyrroles / Q000737:chemistry / Q000494:pharmacology*; D019275:Radiopharmaceuticals / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014227:Triazines / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D002250:Carbon Radioisotopes; D047428:Protein Kinase Inhibitors; D011758:Pyrroles; D019275:Radiopharmaceuticals; D014227:Triazines; D048308:Mitogen-Activated Protein Kinase 14
keywords: Cancer; Carbon-11-labeled 4-(phenylamino)-pyrrolo[2,1-f][1,2,4]triazine derivatives; Diabetes; Inflammation; Positron emission tomography (PET); p38α mitogen-activated protein kinase (MAPK)