ABSTRACT
A series of pyrazinones were prepared and evaluated as potential CRF(1)R PET imaging agents. Optimization of their CRF(1)R binding potencies and octanol-phosphate buffer phase distribution coefficients are discussed herein.
Subject(s)
Positron-Emission Tomography , Pyrazines/pharmacology , Receptors, Corticotropin-Releasing Hormone/antagonists & inhibitors , Animals , Brain , Humans , Molecular Structure , Pyrazines/chemistry , Rats , Receptors, Corticotropin-Releasing Hormone/chemistryABSTRACT
Based on a favorable balance between CRF-R1 affinity, lipophilicity and metabolic stability, compound 10 was evaluated for potential development as PET radioligand. Compound [(18)F]10 was prepared with high radiochemical purity and showed promising binding properties in rat brain imaging experiments.
Subject(s)
Aniline Compounds/chemistry , Fluorine Radioisotopes , Positron-Emission Tomography , Pyrazines/chemistry , Pyrazoles/chemistry , Animals , Brain/diagnostic imaging , Brain/metabolism , Fluorine Radioisotopes/blood , Imaging, Three-Dimensional , Molecular Structure , Pyrazoles/metabolism , Rats , Tissue DistributionABSTRACT
A series of N-fluoroalkyl-8-(6-methoxy-2-methylpyridin-3-yl)-2,7-dimethyl-N-alkylpyrazolo[1,5-a][1,3,5]triazin-4-amines were prepared and evaluated as potential CRF(1)R PET imaging agents. Optimization of their CRF(1)R binding potencies and octanol-phosphate buffer phase distribution coefficients resulted in discovery of analog 7e (IC(50)=6.5 nM, logD=3.5).
