Synthesis of carbon-11 labeled fluorinated 2-arylbenzothiazoles as novel potential PET cancer imaging agents.
Fluorinated 2-arylbenzothiazoles are new potential antitumor drugs, which show potent and selective inhibitory activity against breast, lung, and colon cancer cell lines. Carbon-11 labeled fluorinated 2-arylbenzothiazoles may serve as novel probes for positron emission tomography (PET) to image tyrosine kinase in cancers. The preparation of 4-fluorinated 2-arylbenzothiazoles 4-fluoro-2-(3-benzloxy-4-methoxyphenyl)benzothiazole (6a) and 4-fluoro-2-(3,4-dimethoxyphenyl)benzothiazole (6b) was achieved by a modification of Jacobson thioanilide radical cyclization chemistry. Hydrogenolytic cleavage of the benzyl ether group of compound 6a using H(2)/Pd-C provided the precursor 4-fluoro-2-(3-hydroxy-4-methoxyphenyl)benzothiazole (7) for radiolabeling. Synthesis of radiolabeling precursors and the reference standards 5- and 6-fluorinated arylbenzothiazoles (11c-n) was achieved via the reaction of o-aminothiophenol disulfides with substituted benzaldehydes under reducing conditions. The target radiotracers carbon-11 labeled 4-, 5-, and 6-fluorinated arylbenzothiazoles (3-[(11)C]6b, 4-[(11)C]11c, 3-[(11)C]11c, 5-[(11)C]11f, 4-[(11)C]11f, 4-[(11)C]11i, 3-[(11)C]11i, 5-[(11)C]11l, and 4-[(11)C]11l) were prepared by O-[(11)C]methylation of the phenolic hydroxyl precursors (7, 11d, 11e, 11g, 11h, 11j, 11k, 11m, and 11n) with [(11)C]methyl triflate and isolated by solid-phase extraction (SPE) purification in 30-55% radiochemical yields.
Wang
Min
M
Department of Radiology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Gao
Mingzhang
M
Mock
Bruce H
BH
Miller
Kathy D
KD
Sledge
George W
GW
Hutchins
Gary D
GD
Zheng
Qi-Huang
QH
D000818:Animals; D052160:Benzothiazoles / Q000138:chemical synthesis* / Q000737:chemistry; D002250:Carbon Radioisotopes; D006801:Humans; D009369:Neoplasms / Q000000981:diagnostic imaging*; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000737:chemistry; D014055:Tomography, Emission-Computed
C516702:4-fluoro-2-(3,4-dimethoxyphenyl)benzothiazole; C516701:4-fluoro-2-(3-benzyloxy-4-methoxyphenyl)benzothiazole; D052160:Benzothiazoles; D002250:Carbon Radioisotopes; D019275:Radiopharmaceuticals; C005465:benzothiazole