Opioids are widely used for pain management in moderate-to-severe pain. However, opioids
are associated with adverse events, such as constipation and emesis/vomiting. To reduce these undesired
effects, a structure–activity relationship study of morphinan derivatives was conducted, and a
promising lead compound with inhibitory effects on opioid receptors was obtained. Further improvement
in the potency and pharmacokinetic profiles of the lead compound led to the discovery of
naldemedine, which showed anti-constipation and anti-emetic effects against these adverse events that
were induced by morphine without influencing morphine’s analgesic effect. Naldemedine was launched
in Japan and the USA in 2017 and in the EU in 2019, for treating opioid-induced constipation.
Synthesis and preliminary structure-activity relationship study of 3-methylquinazolinone derivatives as EGFR inhibitors with enhanced antiproliferative activities against tumour cells