Development of orally active oxytocin antagonists: studies on 1-(1-{4-[1-(2-methyl-1-oxidopyridin-3-ylmethyl) piperidin-4-yloxy]-2-methoxybenzoyl} piperidin-4-yl)-1, 4- …

…, RM Freidinger, SN Gallicchio, JP Guare…

Index: Bell, Ian M.; Erb, Jill M.; Freidinger, Roger M.; Gallicchio, Steven N.; Guare, James P.; Guidotti, Maribeth T.; Halpin, Rita A.; Hobbs, Doug W.; Homnick, Carl F.; Kuo, Michelle S.; Lis, Edward V.; Mathre, David J.; Michelson, Stuart R.; Pawluczy, Joseph M.; Pettibone, Douglas J.; Reiss, Duane R.; Vickers, Stanley; Williams, Peter D.; Woyden, Carla J. Journal of Medicinal Chemistry, 1998 , vol. 41, # 12 p. 2146 - 2163

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Citation Number: 59

Abstract

The previously reported oxytocin antagonist L-371,257 (2) has been modified at its acetylpiperidine terminus to incorporate various pyridine N-oxide groups. This modification has led to the identification of compounds with improved pharmacokinetics and excellent oral bioavailability. The pyridine N-oxide series is exemplified by L-372,662 (30), which possessed good potency in vitro (K i= 4.1 nM, cloned human oxytocin receptor) and in ...