Influence of chain length on the activity of tripeptidomimetic antagonists for CXC chemokine receptor 4 (CXCR4)
Peer reviewed, Journal article
MetadataShow full item record
- Department of Chemistry 
Original versionBaumann M, Hussain MM, Henne N, Garrote DM, Karlshøj S, Fossen T, Rosenkilde MM, Våbenø J, Haug BE. Influence of chain length on the activity of tripeptidomimetic antagonists for CXC chemokine receptor 4 (CXCR4). Bioorganic & Medicinal Chemistry. 2017;25(2):646-657 https://doi.org/10.1016/j.bmc.2016.11.036
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.
Under embargo until: 21.11.2018