Format

Send to

Choose Destination
J Med Chem. 2003 May 8;46(10):1918-30.

Design of selective peptidomimetic agonists for the human orphan receptor BRS-3.

Author information

1
Institut für Organische Chemie und Biochemie, Technische Universität München, Lichtenbergstrasse 4, 85747 Garching, Germany.

Abstract

New tool substances may help to unravel the physiological role of the human orphan receptor BRS-3 and its possible use as a drug target for the treatment of obesity and cancer. In continuation of our work on BRS-3, the solid- and solution-phase synthesis of a library of low molecular weight peptidomimetic agonists based on the recently developed short peptide agonist 4 is described. Functional potencies of the compounds were determined measuring calcium mobilization in a fluorometric imaging plate reader (FLIPR) assay. Focusing on the N-terminus, the d-Phe-Gln moiety of 4 was modified in a combinatorial SAR-oriented medicinal chemistry approach. With the incorporation of N-arylated glycine and alanine building blocks azaglycine, piperazine, or piperidine and the synthesis of semicarbazides and semicarbazones, a number of highly potent and selective compounds with a reduced number of peptide bonds were obtained, which also should have enhanced metabolic stability.

PMID:
12723954
DOI:
10.1021/jm0210921
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for American Chemical Society
Loading ...
Support Center