par Van Cauwenberghe, Sylvia;Simonin, Frédéric;Cluzeau, Jérôme;Becker, Jérôme ;Lubell, William W.D.;Tourwe, Dirk
Référence Journal of medicinal chemistry, 47, 7, page (1864-1867)
Publication Publié, 2004-03
Référence Journal of medicinal chemistry, 47, 7, page (1864-1867)
Publication Publié, 2004-03
Article révisé par les pairs
Résumé : | The structure-activity requirements of the ORL1 antagonist Ac-Arg-D-Cha-Qaa-D-Arg-D-p-ClPhe-NH2 4 were investigated by varying the position, structure, and charge of the Arg residues. Attempts to abridge the peptide by removal of the Arg, D-Cha, and D-p-ClPhe residues abolished affinity for the ORL1 receptor, whereas deletion of the acetamido N-terminus maintained receptor affinity and selectivity. This series of analogues has provided an improved potent and selective ORL1 receptor antagonist, Ac-Cit-D-Cha-Qaa-D-Arg-D-p-ClPhe-NH2. |