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 V(1A) and V(2) 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.

Identification of a urea bioisostere of a triazole oxytocin antagonist.

A series of azetidine ureas were investigated as potential bioisosteres of previously reported azetidinyltriazole oxytocin antagonists. Although potency was somewhat reduced in several close-in analogues, one compound, 9, was both a potent oxytocin antagonist and demonstrated significant selectivity over the closely related vasopressin V(1A) receptor.

Design and optimization of potent, selective antagonists of Oxytocin.

A novel series of Oxytocin antagonists are described. This series was identified through pharmacophoric overlap of in-house and literature antagonists. Subsequent optimization led to a series of potent, selective antagonists. Several analogues displayed oral bioavailability in vivo in the rat.

Triazole oxytocin antagonists: identification of aryl ether replacements for a biaryl substituent.

Several potent aryl ether/triazole oxytocin antagonists are described. The lead compound in this series had significantly improved aqueous solubility over related systems containing a biaryl substituent.