Pyrazolo-[1,5- a]-1,3,5-triazine corticotropin-Releasing factor (CRF) receptor ligands

The syntheses and rat CRF receptor binding affinities of ‘retro-pyrazolotriazine’ corticotropin-releasing factor (CRF) ligands 4 are reported. Some have high affinity for rat CRF receptors ( K i≤10 nM). The data provide additional support for the hypothesis that it is possible to interchange isosteric cores with similar electronic properties in the design of high-affinity CRF receptor ligands, provided the peripheral pharmacophore elements are maintained in the same three-dimensional array. The syntheses and rat CRF receptor binding affinities of compounds 4 are described. Example 4j (R 1=R 2=Pr, R 3=Cl, R 4=R 5=OMe) had very high affinity ( K i=0.7 nM).