Nonpeptide oxytocin antagonists: analogs of L-371,257 with improved potency

P D Williams; M G Bock; B E Evans; R M Freidinger; S N Gallicchio; M T Guidotti; M A Jacobson; M S Kuo; M R Levy; E V Lis; S R Michelson; J M Pawluczyk; D S Perlow; D J Pettibone; A G Quigley; D R Reiss; C Salvatore; K J Stauffer; C J Woyden

doi:10.1016/s0960-894x(99)00181-x

Nonpeptide oxytocin antagonists: analogs of L-371,257 with improved potency

Bioorg Med Chem Lett. 1999 May 3;9(9):1311-6. doi: 10.1016/s0960-894x(99)00181-x.

Affiliation

¹ Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486, USA.

PMID: 10340620
DOI: 10.1016/s0960-894x(99)00181-x

Abstract

Structure-activity studies on the oxytocin antagonist 1 (L-371,257; Ki = 9.3 nM) have led to the identification of a related series of compounds containing an ortho-trifluoroethoxyphenylacetyl core which are orally bioavailable and have significantly improved potency in vitro and in vivo, e.g., compound 8 (L-374,943; Ki = 1.4 nM).

MeSH terms

Animals
Benzoxazines
Cell Line
Humans
Inhibitory Concentration 50
Kinetics
Oxazines / chemical synthesis*
Oxazines / pharmacokinetics*
Oxytocin / antagonists & inhibitors*
Piperidines / chemical synthesis*
Piperidines / pharmacokinetics*
Rats
Structure-Activity Relationship

Substances

Benzoxazines
L 371257
Oxazines
Piperidines
Oxytocin