Lipophilicity coefficients of potential tumor imaging agents, positron-labeled O6-benzylguanine derivatives

Xuan Liu, Ji Quan Wang, Qi-Huang Zheng

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Novel radiolabeled O6-benzylguanine (O6-BG) derivatives, 6-O-[11C]-[(methoxymethyl)benzyl]guanines ([11C]p-O6-MNMG, 1a; [11C]m-O6-MMBG, 1b; [11C]o-O6-MMBG, 1c), 2-amino-6-O-[11C]-[(methoxymethyl)benzyloxy]-9-methyl purines ([11C]p-O6-AMMP, 2a; [11C]m-O6-AMMP, 2b; [11C]o-O6-AMMP, 2c), 2-amino-6-O-[11C]-[(methoxymethyl)benzyloxy]-9-benzyl purines ([11C]p-O6-AMBP, 3a; [11C]m-O6-AMBP, 3b; [11C]o-O6-AMBP, 3c), 2-amino-6-O-benzyloxy-9-[11C]-[(methoxycarbonyl)methyl]purine ([11C]ABMMP, 4), and 2-amino-6-O-benzyloxy-9-[11C]- [(4′-methoxycarbonyl)benzyl]purine ([11C]ABMBP, 5), have been synthesized for evaluation as potential novel positron emission tomography tumor imaging agents. The ability of O6-BG analogs to penetrate the blood-brain barrier in brain tumor could be due, at least in part, to their lipophilicity. In this paper, we measured lipophilicity coefficients (log P) of compounds 1-5 by the C18 HPLC method. These log P values were compared, and correlations between lipophilicity and biological activity of selected analogs were made. The results suggest the appropriate level of lipophilic character in this class of compounds as useful imaging agents appears to be in the range of 1.4-2.6.

Original languageEnglish
Pages (from-to)379-384
Number of pages6
JournalBiomedical Chromatography
Volume19
Issue number5
DOIs
StatePublished - Jun 2005

Fingerprint

Purines
Positrons
Tumors
Electrons
Derivatives
Imaging techniques
Positron emission tomography
Guanine
Bioactivity
Blood-Brain Barrier
Brain Neoplasms
Positron-Emission Tomography
Brain
Neoplasms
High Pressure Liquid Chromatography
purine
O(6)-benzylguanine

Keywords

  • HPLC
  • Lipophilicity coefficients
  • O-benzylguanine derivatives
  • Positron emission tomography
  • Tumor imaging agents

ASJC Scopus subject areas

  • Analytical Chemistry
  • Clinical Biochemistry
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Pharmacology

Cite this

Lipophilicity coefficients of potential tumor imaging agents, positron-labeled O6-benzylguanine derivatives. / Liu, Xuan; Wang, Ji Quan; Zheng, Qi-Huang.

In: Biomedical Chromatography, Vol. 19, No. 5, 06.2005, p. 379-384.

Research output: Contribution to journalArticle

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abstract = "Novel radiolabeled O6-benzylguanine (O6-BG) derivatives, 6-O-[11C]-[(methoxymethyl)benzyl]guanines ([11C]p-O6-MNMG, 1a; [11C]m-O6-MMBG, 1b; [11C]o-O6-MMBG, 1c), 2-amino-6-O-[11C]-[(methoxymethyl)benzyloxy]-9-methyl purines ([11C]p-O6-AMMP, 2a; [11C]m-O6-AMMP, 2b; [11C]o-O6-AMMP, 2c), 2-amino-6-O-[11C]-[(methoxymethyl)benzyloxy]-9-benzyl purines ([11C]p-O6-AMBP, 3a; [11C]m-O6-AMBP, 3b; [11C]o-O6-AMBP, 3c), 2-amino-6-O-benzyloxy-9-[11C]-[(methoxycarbonyl)methyl]purine ([11C]ABMMP, 4), and 2-amino-6-O-benzyloxy-9-[11C]- [(4′-methoxycarbonyl)benzyl]purine ([11C]ABMBP, 5), have been synthesized for evaluation as potential novel positron emission tomography tumor imaging agents. The ability of O6-BG analogs to penetrate the blood-brain barrier in brain tumor could be due, at least in part, to their lipophilicity. In this paper, we measured lipophilicity coefficients (log P) of compounds 1-5 by the C18 HPLC method. These log P values were compared, and correlations between lipophilicity and biological activity of selected analogs were made. The results suggest the appropriate level of lipophilic character in this class of compounds as useful imaging agents appears to be in the range of 1.4-2.6.",
keywords = "HPLC, Lipophilicity coefficients, O-benzylguanine derivatives, Positron emission tomography, Tumor imaging agents",
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AB - Novel radiolabeled O6-benzylguanine (O6-BG) derivatives, 6-O-[11C]-[(methoxymethyl)benzyl]guanines ([11C]p-O6-MNMG, 1a; [11C]m-O6-MMBG, 1b; [11C]o-O6-MMBG, 1c), 2-amino-6-O-[11C]-[(methoxymethyl)benzyloxy]-9-methyl purines ([11C]p-O6-AMMP, 2a; [11C]m-O6-AMMP, 2b; [11C]o-O6-AMMP, 2c), 2-amino-6-O-[11C]-[(methoxymethyl)benzyloxy]-9-benzyl purines ([11C]p-O6-AMBP, 3a; [11C]m-O6-AMBP, 3b; [11C]o-O6-AMBP, 3c), 2-amino-6-O-benzyloxy-9-[11C]-[(methoxycarbonyl)methyl]purine ([11C]ABMMP, 4), and 2-amino-6-O-benzyloxy-9-[11C]- [(4′-methoxycarbonyl)benzyl]purine ([11C]ABMBP, 5), have been synthesized for evaluation as potential novel positron emission tomography tumor imaging agents. The ability of O6-BG analogs to penetrate the blood-brain barrier in brain tumor could be due, at least in part, to their lipophilicity. In this paper, we measured lipophilicity coefficients (log P) of compounds 1-5 by the C18 HPLC method. These log P values were compared, and correlations between lipophilicity and biological activity of selected analogs were made. The results suggest the appropriate level of lipophilic character in this class of compounds as useful imaging agents appears to be in the range of 1.4-2.6.

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