ABSTRACT
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)< or =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.
Subject(s)
Pyrazoles/chemistry , Receptors, Corticotropin-Releasing Hormone/drug effects , Triazines/chemical synthesis , Animals , Binding Sites , Cell Membrane/drug effects , Cell Membrane/metabolism , Corticotropin-Releasing Hormone/chemistry , Corticotropin-Releasing Hormone/pharmacology , In Vitro Techniques , Ligands , Models, Molecular , Molecular Structure , Rats , Receptors, Corticotropin-Releasing Hormone/classification , Triazines/pharmacologyABSTRACT
Potent, small molecule A beta inhibitors have been prepared that incorporate an alanine core bracketed by an N-terminal arylacetyl group and various C-terminal amino alcohols. The compounds exhibit stereospecific inhibition as demonstrated in an in vitro assay.
