View : 287 Download: 0
The carbonate analogues of 5 '-halogenated resiniferatoxin as TRPV1 ligands
- The carbonate analogues of 5 '-halogenated resiniferatoxin as TRPV1 ligands
- Lim, Kwang Su; Lee, Hobin; Kim, Sung Eun; Ha, Tae-Hwan; Ann, Jihyae; Son, Karam; Choi, Sun; Sun, Wei; Pearce, Larry V.; DeAndrea-Lazarus, Ian A.; Blumberg, Peter M.; Lee, Jeewoo
- Ewha Authors
- SCOPUS Author ID
- Issue Date
- Journal Title
- EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
- EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY vol. 68, pp. 233 - 243
- TRPV1 agonist; TRPV1 antagonist; Partial agonist; Halogenation; Resiniferatoxin; Molecular modelling
- ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
- SCI; SCIE; SCOPUS
- Document Type
Show the fulltext
- A series of carbonate analogues of 5'-halogenated RTX have been investigated in order to examine the effect of the carbonate group as a linker and the role of halogens in the reversal of activity from agonism to antagonism for rat and human TRPV1 heterologously expressed in Chinese hamster ovary cells. The carbonate analogues showed similar activities to the corresponding RTX derivatives in rat TRPV1 but lower potency in human TRPV1. 5-Halogenation converted the agonists to partial agonists or full antagonists and the extent of antagonism reflected the order of I > Br > Cl > F, with a somewhat greater extent of antagonism for the derivatives of the 4-amino RTX surrogates compared to the corresponding derivatives of RTX itself. The carbonate analogues of I-RTX: (60) and 5-bromo-4-amino-RTX (66) were potent and full antagonists with K-i(ant) = 2.23 and 2.46 nM, respectively, for rat TRPV1, which were ca. 5-fold more potent than I-RTX (2) under our conditions. The conformational analysis of the I-RTX-carbonate (60) indicated that its bent conformation was similar to that of I-RTX, consistent with compound 60 and I-RTX showing comparable potent antagonism. (C) 2013 Elsevier Masson SAS. All rights reserved.
- Appears in Collections:
- 약학대학 > 약학과 > Journal papers
- Files in This Item:
There are no files associated with this item.
- RIS (EndNote)
- XLS (Excel)
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.