期刊
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
卷 21, 期 6, 页码 1807-1809出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2011.01.074
关键词
Permeability; NKA antagonists; Hydrogen bond
资金
- MIUR, Ministero dell'Istruzione, dell'Universita e della Ricerca [4579/DSPAR/01]
Starting from in-house capped tripeptide libraries, we have developed two series of compounds as potent antagonists of the hNK(2) receptor with a reduced peptide character. These two series maintained a crucial amide bond, which could not be methylated or substituted with classical isostere without a dramatic loss in binding affinity, very likely due conformational changes. We report here the planning, synthesis and evaluation of molecules belonging to the selected chemical series, which contain a strategically placed hydrogen bond acceptor. The aim of the work was to improve membrane permeability via the formation of an intramolecular hydrogen bonding, and at the same time to maintain the structural characteristics geometry and polarity of the amide linkage so as to retain a relevant binding affinity for the biological target. (C) 2011 Elsevier Ltd. All rights reserved.
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