Eur J Med Chem 2003 May 01;385:481-93. doi: 10.1016/s0223-5234(03)00062-x.

Design, synthesis, and biological evaluation of non-peptidic ligands at the Xenopus laevis skin-melanocortin receptor.

???displayArticle.abstract???
Taking the tripeptide D-Trp-Arg-Leu-NH(2) as a lead for a Xenopus laevis skin-melanocortin (MC) receptor antagonist, thirteen non-peptidic compounds were synthesized and biologically evaluated at Xenopus laevis melanophores. Six competitive antagonists (shown by Schild analysis) and one partial agonist were identified with moderate activity (IC(50): 5-10 microM). Tryptophanamides with aliphatic side chains were inactive whereas basic residues restored activity. Introducing an imidazole residue yielded partial agonist activity (EC50: 32 microM). Interestingly, constraining the inactive S-tryptophan-isoamylamide to a beta-carboline ring yielded an MC receptor antagonist (42). The specificity for MC receptors was tested at various G-protein coupled receptors. In conclusion, the synthesis of non-peptidic MC receptor antagonists is described which may serve as lead compounds for further studies.

???displayArticle.pubmedLink??? 12767598
???displayArticle.link??? Eur J Med Chem