Synthesis of new 4-HPR analogues and use of PET imaging to support the development of drug candidates

Fenretinide (4-HPR) is a synthetic retinoid which has been investigated for decades as an anticancer agent and more recently as a potential drug to treat metabolic syndrome. Here we synthesised a library of 4-HPR analogues - using a SAR approach - with the final goal to improve both anti-cancer activity and anti- obesity/diabetes properties of 4-HPR. Among the designed 4-HPR analogues, we selected the click-type analogue 3b, which is amenable to radiofluorination, to develop a PET tracer to further investigate the pharmacological profile of 4-HPR and analogues in vivo