Synthesis Binding Affinity Radiolabeling and MicroPET Evaluation of 4-(2-Substituted-4-substituted)-8-(dialkylamino)-6-methyl-1-substituted-34-dihydropyrido23-bpyrazin-2(1H)-ones as Ligands for Brain Corticotropin-Releasing Factor Type-1 (CRF1) Receptors

摘要

Compounds >1–14 were synthesized in a search for high-affinity CRF1 receptor ligands that could be radiolabeled with ¹¹C or ¹⁸F for use as positron emission tomography (PET) radiotracers. Derivatives of >2 were developed which contained amide N-fluoroalkyl substituents. Compounds [¹⁸F]>24 and [¹⁸F]>25 were found to have appropriate lipophilicities of logP7.4 = 2.2 but microPET imaging with [¹⁸F]>25 demonstrated limited brain uptake.