Lipophilicity coefficients of potential tumor imaging agents, positron-labeled O(6)-benzylguanine derivatives.
Novel radiolabeled O(6)-benzylguanine (O(6)-BG) derivatives, 6-O-[(11)C]-[(methoxymethyl)benzyl]guanines ([(11)C]p-O(6)-MMBG, 1a; [(11)C]m-O(6)-MMBG, 1b; [(11)C]o-O(6)-MMBG, 1c), 2-amino-6-O-[(11)C]-[(methoxymethyl)benzyloxy]-9-methyl purines ([(11)C]p-O(6)-AMMP, 2a; [(11)C]m-O(6)-AMMP, 2b; [(11)C]o-O(6)-AMMP, 2c), 2-amino-6-O-[(11)C]-[(methoxymethyl)benzyloxy]-9-benzyl purines ([(11)C]p-O(6)-AMBP, 3a; [(11)C]m-O(6)-AMBP, 3b; [(11)C]o-O(6)-AMBP, 3c), 2-amino-6-O-benzyloxy-9-[(11)C]-[(methoxycarbonyl)methyl]purine ([(11)C]ABMMP, 4), and 2-amino-6-O-benzyloxy-9-[(11)C]-[(4'-methoxycarbonyl)benzyl]purine ([(11)C]ABMBP, 5), have been synthesized for evaluation as potential novel positron emission tomography tumor imaging agents. The ability of O(6)-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 C(18) 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.
Liu
Xuan
X
Department of Radiology, Indiana University School of Medicine, L-3 Room 202, Indianapolis, IN 46202, USA.
Wang
Ji-Quan
JQ
Zheng
Qi-Huang
QH
D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors; D001593:Benzyl Compounds / Q000737:chemistry*; D001943:Breast Neoplasms / Q000201:enzymology; D002250:Carbon Radioisotopes; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D006147:Guanine / Q000031:analogs & derivatives*; D006367:HeLa Cells; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000737:chemistry*
D001593:Benzyl Compounds; D002250:Carbon Radioisotopes; D008055:Lipids; D019275:Radiopharmaceuticals; D006147:Guanine; D019883:Alkyl and Aryl Transferases; C050956:DNA alkyltransferase