Synthesis and in vivo evaluation of [11C]SN003 as a PET ligand for CRF1 receptors

  • Bioorg Med Chem. 2006 Jun 15;14(12):4029-34. doi: 10.1016/j.bmc.2006.02.019.
J S Dileep Kumar  1 ,  Vattoly J Majo ,  Gregory M Sullivan ,  Jaya Prabhakaran ,  Norman R Simpson ,  Ronald L Van Heertum ,  J John Mann ,  Ramin V Parsey
Affiliations
  • 1. Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, USA. [email protected]
PMID: 16529935 DOI: 10.1016/j.bmc.2006.02.019
Abstract

Synthesis and evaluation of [O-methyl-11C](4-methoxy-2-methylphenyl)[1-(1-methoxymethylpropyl)-6-methyl-1H-[1,2,3]triazolo[4,5-c]pyridin-4-yl]amine or [11C]SN003 ([11C]6), as a PET imaging agent for CRF1 receptors, in baboons is described. 4-[1-(1-Methoxymethylpropyl)-6-methyl-1H-[1,2,3]triazolo[4,5-c]pyridin-4-ylamino]-3-methylphenol (5), the precursor molecule for the radiolabeling, was synthesized from 2,4-dichloro-6-methyl-3-nitropyridine in seven steps with 20% overall yield. The total time required for the synthesis of [11C]SN003 is 30 min from EOB using [11C]methyl triflate in the presence of NaOH in acetone. The yield of the synthesis is 22% (EOS) with >99% chemical and radiochemical purities and a specific activity of >2000 Ci/mmol. PET studies in baboon show that [11C]6 penetrates the BBB and accumulates in brain. No detectable specific binding was observed, likely due to the rapid metabolism or low density of CRF1 receptors in primate brain.

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