The results demonstrate proof-of-concept in the treatment of threatened spontaneous preterm labour [6] The oral bioavailability of retosiban is in the order of 100% in the rat with a half life of 1.4 hours.

Retosiban is the (3R, 6R, 7R)-isomer and is a sub-nanomolar (Ki = 0.65 nM) oxytocin receptor antagonist, while the (3R, 6R, 7S)-isomer where the stereochemistry in the amide side-chain at C-7 is inverted, is 10-fold less potent.

This structure–activity relationship (SAR) is supported by the crystal structure of the human oxytocin receptor in complex with retosiban, [7] where the lipophilic indanyl substituent penetrates into a deep, mainly hydrophobic crevice at the bottom of the binding pocket, while the oxazol-morpholine amide moiety is closest to the extracellular surface.

In the short lab-scale and highly stereoselective synthesis of Retosiban 8 the linear peptide 5 is formed by the four-component Ugi reaction of the carboxybenzyl (Cbz) protected R-indanylglycine 1, D-alloisoleucine methyl ester hydrochloride 2, 2-methyloxazole-4-carboxaldehyde 3 and 2-benzyloxyphenylisonitrile 4.

Hydrogenation to remove the Cbz and benzyl protecting groups, enabled cyclization of the linear peptide 5 to occur to give the phenolic cyclic dipeptide 6.