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.
Brown
Alan
A
Discovery Chemistry, Pfizer Global Research and Development, Sandwich, United Kingdom. Alan.D.Brown@pfizer.com
Ellis
Dave
D
Wallace
Olga
O
Ralph
Michael
M
D000577:Amides / Q000737:chemistry* / Q000494:pharmacology*; D065092:Antidiuretic Hormone Receptor Antagonists; D008958:Models, Molecular; D015394:Molecular Structure; D010121:Oxytocin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D017483:Receptors, Vasopressin / Q000378:metabolism; D014230:Triazoles / Q000037:antagonists & inhibitors* / Q000378:metabolism
D000577:Amides; D065092:Antidiuretic Hormone Receptor Antagonists; D017483:Receptors, Vasopressin; D014230:Triazoles; D010121:Oxytocin