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J Med Chem. 2004 Mar 25;47(7):1864-7.

Structure-activity study of the ORL1 antagonist Ac-Arg-D-Cha-Qaa-D-Arg-D-p-ClPhe-NH2.

Author information

1
Eenheid Organische Chemie, Vrije Universiteit Brussel, 2, Pleinlaan, B-1050, Brussels, Belgium.

Abstract

The structure-activity requirements of the ORL1 antagonist Ac-Arg-D-Cha-Qaa-D-Arg-D-p-ClPhe-NH(2) 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-NH(2).

PMID:
15027881
DOI:
10.1021/jm031034v
[Indexed for MEDLINE]

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