Bioorganic & Medicinal Chemistry 2012-01-01

Radiosynthesis of [13N]dantrolene, a positron emission tomography probe for breast cancer resistant protein, using no-carrier-added [13N]ammonia.

Katsushi Kumata, Masanao Ogawa, Makoto Takei, Masayuki Fujinaga, Yuichiro Yoshida, Nobuki Nengaki, Toshimitsu Fukumura, Kazutoshi Suzuki, Ming-Rong Zhang

Index: Bioorg. Med. Chem. 20(1) , 305-10, (2012)

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Abstract

Dantrolene (1) is a substrate for breast cancer resistant protein, which is widely distributed in the blood-brain-barrier, intestine, gall bladder, and liver. PET study with 1 labeled with a positron emitter can be used to visualize BCRP and to elucidate the effect of BCRP on the pharmacokinetics of drugs. The objective of this study was to label 1 using nitrogen-13 ((13)N, a positron emitter; half-life: 9.9min). Using no-carrier-added [(13)N]NH(3) as the labeling agent, we synthesized [(13)N]dantrolene ([(13)N]1) for the first time. The reaction of carbomyl chloride 2b with [(13)N]NH(3) gave an unsymmetrical urea [(13)N]3, followed by cyclization of [(13)N]3 to afford [(13)N]1. Due to its instability, 2b was prepared in situ by treating amine 5 with triphosgene in a ratio of 4 to 1 and used for subsequent [(13)N]ammonolysis without purification.Copyright © 2011 Elsevier Ltd. All rights reserved.