OBE022, an Oral and Selective Prostaglandin F Receptor Antagonist as an Effective and Safe Modality for the Treatment of Preterm Labor.

Preterm birth is the major challenge in obstetrics, affecting ∼10% of pregnancies. Pan-prostaglandin synthesis inhibitors [nonsteroidal anti-inflammatory drugs (NSAIDs)] prevent preterm labor and prolong pregnancy but raise concerns about fetal renal and cardiovascular safety. We conducted preclinical studies examining the tocolytic effect and fetal safety of the oral prodrug candidate OBE022 [()-2-amino-3-methyl-butyric acid ()-3-{[(S)-3-(biphenyl-4-sulfonyl)-thiazolidine-2-carbonyl]-amino}-3-(4-fluoro-phenyl)-propyl ester] and its parent OBE002 [()-3-(biphenyl-4-sulfonyl)-thiazolidine-2-carboxylic acid [(S)-1-(4-fluoro-phenyl)-3-hydroxy-propyl]-amide], both potent and highly selective antagonist of the contractile prostaglandin F (PGF ) receptor (FP).