Synthesis of carbon-11 labeled fluorinated 2-arylbenzothiazoles as novel potential PET cancer imaging agents

Min Wang, Mingzhang Gao, Bruce H. Mock, Kathy Miller, George W. Sledge, Gary Hutchins, Qi-Huang Zheng

Research output: Contribution to journalArticle

101 Citations (Scopus)

Abstract

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 H2/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-[11C]6b, 4-[11C]11c, 3-[11C]11c, 5-[11C]11f, 4-[11C]11f, 4-[11C]11i, 3-[11C]11i, 5-[11C]11l, and 4-[11C]11l) were prepared by O-[11C]methylation of the phenolic hydroxyl precursors (7, 11d, 11e, 11g, 11h, 11j, 11k, 11m, and 11n) with [11C]methyl triflate and isolated by solid-phase extraction (SPE) purification in 30-55% radiochemical yields.

Original languageEnglish
Pages (from-to)8599-8607
Number of pages9
JournalBioorganic and Medicinal Chemistry
Volume14
Issue number24
DOIs
StatePublished - Dec 15 2006

Fingerprint

Positron emission tomography
Positron-Emission Tomography
Carbon
Benzaldehydes
Imaging techniques
Methylation
Cyclization
Solid Phase Extraction
Disulfides
Hydroxyl Radical
Antineoplastic Agents
Ether
Protein-Tyrosine Kinases
Colonic Neoplasms
Purification
Lung Neoplasms
Neoplasms
Cells
Breast Neoplasms
Cell Line

Keywords

  • Cancer imaging
  • Carbon-11
  • Fluorinated 2-arylbenzothiazoles
  • Positron emission tomography (PET)
  • Tyrosine kinase

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Organic Chemistry
  • Drug Discovery
  • Pharmaceutical Science

Cite this

Synthesis of carbon-11 labeled fluorinated 2-arylbenzothiazoles as novel potential PET cancer imaging agents. / Wang, Min; Gao, Mingzhang; Mock, Bruce H.; Miller, Kathy; Sledge, George W.; Hutchins, Gary; Zheng, Qi-Huang.

In: Bioorganic and Medicinal Chemistry, Vol. 14, No. 24, 15.12.2006, p. 8599-8607.

Research output: Contribution to journalArticle

@article{55baec81620d44119c6da6f9757f78b6,
title = "Synthesis of carbon-11 labeled fluorinated 2-arylbenzothiazoles as novel potential PET cancer imaging agents",
abstract = "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 H2/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-[11C]6b, 4-[11C]11c, 3-[11C]11c, 5-[11C]11f, 4-[11C]11f, 4-[11C]11i, 3-[11C]11i, 5-[11C]11l, and 4-[11C]11l) were prepared by O-[11C]methylation of the phenolic hydroxyl precursors (7, 11d, 11e, 11g, 11h, 11j, 11k, 11m, and 11n) with [11C]methyl triflate and isolated by solid-phase extraction (SPE) purification in 30-55{\%} radiochemical yields.",
keywords = "Cancer imaging, Carbon-11, Fluorinated 2-arylbenzothiazoles, Positron emission tomography (PET), Tyrosine kinase",
author = "Min Wang and Mingzhang Gao and Mock, {Bruce H.} and Kathy Miller and Sledge, {George W.} and Gary Hutchins and Qi-Huang Zheng",
year = "2006",
month = "12",
day = "15",
doi = "10.1016/j.bmc.2006.08.026",
language = "English",
volume = "14",
pages = "8599--8607",
journal = "Bioorganic and Medicinal Chemistry",
issn = "0968-0896",
publisher = "Elsevier Limited",
number = "24",

}

TY - JOUR

T1 - Synthesis of carbon-11 labeled fluorinated 2-arylbenzothiazoles as novel potential PET cancer imaging agents

AU - Wang, Min

AU - Gao, Mingzhang

AU - Mock, Bruce H.

AU - Miller, Kathy

AU - Sledge, George W.

AU - Hutchins, Gary

AU - Zheng, Qi-Huang

PY - 2006/12/15

Y1 - 2006/12/15

N2 - 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 H2/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-[11C]6b, 4-[11C]11c, 3-[11C]11c, 5-[11C]11f, 4-[11C]11f, 4-[11C]11i, 3-[11C]11i, 5-[11C]11l, and 4-[11C]11l) were prepared by O-[11C]methylation of the phenolic hydroxyl precursors (7, 11d, 11e, 11g, 11h, 11j, 11k, 11m, and 11n) with [11C]methyl triflate and isolated by solid-phase extraction (SPE) purification in 30-55% radiochemical yields.

AB - 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 H2/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-[11C]6b, 4-[11C]11c, 3-[11C]11c, 5-[11C]11f, 4-[11C]11f, 4-[11C]11i, 3-[11C]11i, 5-[11C]11l, and 4-[11C]11l) were prepared by O-[11C]methylation of the phenolic hydroxyl precursors (7, 11d, 11e, 11g, 11h, 11j, 11k, 11m, and 11n) with [11C]methyl triflate and isolated by solid-phase extraction (SPE) purification in 30-55% radiochemical yields.

KW - Cancer imaging

KW - Carbon-11

KW - Fluorinated 2-arylbenzothiazoles

KW - Positron emission tomography (PET)

KW - Tyrosine kinase

UR - http://www.scopus.com/inward/record.url?scp=33750507472&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33750507472&partnerID=8YFLogxK

U2 - 10.1016/j.bmc.2006.08.026

DO - 10.1016/j.bmc.2006.08.026

M3 - Article

C2 - 16962783

AN - SCOPUS:33750507472

VL - 14

SP - 8599

EP - 8607

JO - Bioorganic and Medicinal Chemistry

JF - Bioorganic and Medicinal Chemistry

SN - 0968-0896

IS - 24

ER -