Design of Potent Oxytocin Antagonists Featuring D-Tryptophan at Position 2

We prepared nine analogues of MCPA-D-Phe-Phe-Ile-Asn-Cys-Pro-Arg-Gly-NH 2 , [MCPA 1 , D-Phe 2 , Phe 3 , Ile 4 , Arg 8 ] oxytocin (MCPA=β-mercapto-β,β-pentamethylenepropionic acid), a potent antagonist of the rat uterotonic action of oxytocin (OT). We replaced D-Phe with D-Trp and made [MCPA 1 ,D-Trp 2 ,Phe 3 ,Ile 4 ,Arg 8 ]OT, which had OT pA 2 of 7.51, somewhat higher than that of the D-Phe 2 antagonist which has OT pA 2 =7.35 in our rat uterotonic assay. Both compounds are equipotent as antagonists of [Arg 8 ] vasopressin in the rat antidiuretic assay