Potential CRF1R PET imaging agents: N-Fluoroalkyl-8-(6-methoxy-2-methylpyridin-3-yl)-2,7-dimethyl-N-alkylpyrazolo[1,5-a][1,3,5]triazin-4-amines

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 CRF1R PET imaging agents. Optimization of their CRF1R binding potencies and octanol–phosphate buffer phase distribution coefficients resulted in discovery of analog 7e (IC50 = 6.5 nM, log D = 3.5).

Graphical abstractA series of N-(3-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 CRF1R PET imaging agents. Optimization of their CRF1R binding potencies and octanol-phosphate buffer phase distribution coefficients resulted in discovery of analog 7e (IC50 = 6.5 nM, log D = 3.5).Figure optionsDownload full-size imageDownload as PowerPoint slide