title: Synthesis and in vivo evaluation of [11C]SN003 as a PET ligand for CRF1 receptors.
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.
authors.affiliation: Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, USA. dk2038@columbia.edu
authors.forename: J S Dileep
authors.initials: JS
authors.lastname: Kumar
authors.forename: Vattoly J
authors.initials: VJ
authors.lastname: Majo
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Sullivan
authors.forename: Jaya
authors.initials: J
authors.lastname: Prabhakaran
authors.forename: Norman R
authors.initials: NR
authors.lastname: Simpson
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Van Heertum
authors.forename: J John
authors.initials: JJ
authors.lastname: Mann
authors.forename: Ramin V
authors.initials: RV
authors.lastname: Parsey
mesh_terms: D000631:Aminopyridines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D002250:Carbon Radioisotopes; D007553:Isotope Labeling / Q000379:methods; D008024:Ligands; D015394:Molecular Structure; D010215:Papio; D049268:Positron-Emission Tomography / Q000379:methods*; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D018019:Receptors, Corticotropin-Releasing Hormone / Q000187:drug effects*; D013997:Time Factors; D014230:Triazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000099052:CRF Receptor, Type 1
chemical_list: C512237:4-(1-(1-methoxymethylpropyl)-6-methyl-1H-(1,2,3)triazolo(4,5-c)pyridin-4-ylamino)-3-methylphenol; D000631:Aminopyridines; D002250:Carbon Radioisotopes; D008024:Ligands; D011725:Pyridines; D018019:Receptors, Corticotropin-Releasing Hormone; C473245:SN003; D014230:Triazoles; D000099052:CRF Receptor, Type 1