The analogs of oxytocin and D-homoarginine vasopressin with bulky substituted phenylalanine in position 2

Summary Solid phase technique on p-methylbenzhydrylamine resin was used for the synthesis of eight analogs of oxytocin and 8-D-homoarginine vasopressin with the non-coded amino acids L- or D-2,3,4,5,6-pentamethylphenylalanine and L- or D-4-phenylphenylalanine in position 2. The preparation of the above mentioned non-coded amino acids is described as well. All eight analogs were found to be potent inhibitors of oxytocin activity in the uterotonicin vitro test in the absence of Mg²⁺ ions. In the uterotonic testin vitro in the presence of Mg²⁺ and in the testin vivo, their potency is strongly decreased or completely abolished. The substances are also weak pressor inhibitors. The L or D configuration does not seem to influence the activity significantly. Abbreviations: All the chiral amino acids unless otherwise stated are of the L-series. Phe(4-Ph) denotes the 4-phenylphenylalanine, Phe(pentaMe) the 2,3,4,5,6-pentamethylphenylalanine, Har the homoarginine, DMF dimethylformamide, OHBT 1-hydroxybenzotriazole and DCC dicylohexyl-carbodiimitz. The Nomenclature and symbols of the amino acids and peptides obey the published recommendations: IUPAC-IUB Joint Commission on Biochemical Nomenclature: Eur. J. Biochem., 138 (1984) 9.