Triazole oxytocin antagonists: Identification of an aryloxyazetidine replacement for a biaryl substituent

A series of aryloxyazetidines, aryloxypyrrolidines and aryloxypiperidines were designed based on structural overlap with previously reported arylpyrazine Oxytocin antagonists. Similarly high levels of Oxytocin antagonism were achievable in these new series. Several aryloxyazetidines also showed high levels of selectivity, with one compound, 25, displaying promising in vivo pharmacokinetics and significantly improved aqueous solubility over related compounds containing a biaryl substituent.

Several potent aryl ether/triazole Oxytocin antagonists are described. One of these compounds, 25, has excellent potency and selectivity, as well as promising in vivo pharmacokinetics and significantly improved aqueous solubility over related systems containing a biaryl substituent.Figure optionsDownload as PowerPoint slide