Identification of amide bioisosteres of triazole Oxytocin antagonists

A series of amides were investigated as potential bioisosteres of previously reported triazole Oxytocin antagonists. A range of potent analogues were identified, although SAR for potency and selectivity over the related V1A and V2 receptors was found to be somewhat divergent from that observed for the corresponding triazole series. The high synthetic accessibility of this new amide series also facilitated the identification of a range of alternative left hand side (biaryl replacement) substituents which gave good levels of Oxytocin antagonism.

Graphical abstractA series of amides, A, were prepared as potential bioisosteres of previously reported triazole Oxytocin antagonists B. A range of potent analogues were identified, although SAR for potency and selectivity over the related V1A and V2 receptors was found to be somewhat divergent from that observed for triazoles B. The high synthetic accessibility of targets A also facilitated the identification of a range of alternative left hand side (R) substituents with good levels of Oxytocin antagonism.Figure optionsDownload full-size imageDownload as PowerPoint slide