Figure 1
From: pKa of opioid ligands as a discriminating factor for side effects

Chemical structures of fentanyl, N-{1-[2-(2,6-difluorphenyl)ethyl]piperidine-4-yl}-N-phenylpropionamide (FF6), (±)-N-[1-(2-fluoro-2-phenylethyl)piperidine-4-yl]-N-phenyl propionamide (FF3) and (±)-N-(3-fluoro-1-phenethylpiperidine-4-yl)-N-phenyl propionamide (NFEPP). The blue circle highlights the tertiary nitrogen atom subjected to pH-dependent protonation in whose vicinity electrons may be withdrawn to reduce the pKa value. The respective isomers of FF3 and NFEPP are shown. Sites of fluorination are indicated as F.