Abstract
Here we report a series of close analogues of our recently published scaffold-based tripeptidomimetic CXCR4 antagonists, containing positively charged guanidino groups in R1 and R2, and an aromatic group in R3. While contraction/elongation of the guanidine carrying side chains (R1 and R2) resulted in loss of activity, introduction of bromine in position 1 on the naphth-2-ylmethyl moiety (R3) resulted in an EC50 of 61 μM (mixture of diastereoisomers) against wild-type CXCR4; thus, the antagonistic activity of these tripeptidomimetics seems to be amenable to optimization of the aromatic moiety. Moreover, for analogues carrying a naphth-2-ylmethyl substituent, we observed that a Pictet-Spengler like cyclization side reaction depended on the nature of the R1 substituent.
Original language | English |
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Journal | Bioorganic & Medicinal Chemistry |
Volume | 25 |
Issue number | 2 |
Pages (from-to) | 646-657 |
ISSN | 0968-0896 |
DOIs | |
Publication status | Published - 15 Jan 2017 |
Keywords
- CXCR4 antagonist
- Peptidomimetic
- Scaffold