The chiral isomers of the two potent simplified RTX-based vanilloids, compounds 2 and 3, were synthesized employing highly enantioselective PTC alkylation and evaluated as hTRPV1 ligands. The analysis indicated that the R-isomer was the eutomer in binding affinity and functional activity. The agonism of compound 2R was comparable to that of RTX. Docking analysis of the chiral isomers of 3 suggested the basis for its stereospecific activity and the binding mode of 3R.
Bibliographical noteFunding Information:
This research was supported by the National Research Foundation of Korea (NRF) Grant ( 2007-0056817 ) and NLRL program Grant ( 2011-0028885 ) funded by the Korea government MSIP, and was supported in part by the Intramural Research Program of the National Institutes of Health, Center for Cancer Research, National Cancer Institute (Project Z1A BC 005270).
- Molecular modeling
- TRPV1 antagonist
- Vanilloid receptor 1