title: Triazole oxytocin antagonists: Identification of an aryloxyazetidine replacement for a biaryl substituent.
abstract: 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.
authors: Discovery Chemistry, Pfizer Global Research and Development, Sandwich, United Kingdom. Alan.D.Brown@pfizer.com
authors: Alan
authors: A
authors: Brown
authors: T Bruce
authors: TB
authors: Brown
authors: Andrew
authors: A
authors: Calabrese
authors: Dave
authors: D
authors: Ellis
authors: Nicholas
authors: N
authors: Puhalo
authors: Michael
authors: M
authors: Ralph
authors: Lesa
authors: L
authors: Watson
mesh_terms: D000284:Administration, Oral; D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D001384:Azetidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D004285:Dogs; D006801:Humans; D008862:Microsomes, Liver / Q000378:metabolism; D010121:Oxytocin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D017483:Receptors, Vasopressin / Q000378:metabolism; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics
chemical_list: D065092:Antidiuretic Hormone Receptor Antagonists; D001384:Azetidines; D017483:Receptors, Vasopressin; D014230:Triazoles; D010121:Oxytocin