Document Report Card

ID: ALA1126670

Journal: J Med Chem

Title: Cyclic peptides as selective tachykinin antagonists.

Authors: Williams BJ, Curtis NR, McKnight AT, Maguire JJ, Young SC, Veber DF, Baker R.

Abstract: Twenty homodetic cyclic peptides based on the C-terminal sequence of substance P were prepared (Table I) by a combination of solid-phase techniques and cyclizations using azide coupling procedures. Incorporation of dipeptide mimics based on substituted gamma-lactams were used in some cases to restrict their conformational mobility. Five of these cyclic peptides were shown to have high tachykinin antagonist activity (pA2 > 6) at NK-2 receptors (rat vas deferens). The two most potent of this series, XVII, cyclo(Gln-Trp-Phe-Gly-Leu-Met) (pA2 = 8.1), and I cyclo(Gln-Trp-Phe(R)Gly[ANC-2]Leu-Met) (pA2 = 6.7), were selective for NK-2 receptors compared with the other tachykinin receptors (Table II).

CiteXplore: 7678430

DOI: 10.1021/jm00053a001