- BENZAMIDE TRPA1 ANTAGONISTS
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Compounds of formula I, pharmaceutically acceptable salts thereof, diastereomers, enantiomers, or mixtures thereof: wherein R, X, Y, Z, n and A are as defined in the specification, as well as pharmaceutical compositions including the compounds are prepared. They are useful in therapy, in particular in the management of pain.
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Page/Page column 83
(2014/12/12)
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- N-1-Alkyl-2-oxo-2-aryl amides as novel antagonists of the TRPA1 receptor
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A series of potent antagonists of the ion channel transient receptor potential A1 (TRPA1) was developed by modifying lead structure 16 that was discovered by high-throughput screening. Based on lead compound 16, a SAR was established, showing a narrow region at the nitro-aromatic R1 moiety and at the warhead, while the R2 side had a much wider scope including ureas and carbamates. Compound 16 inhibits Ca2+-activated TRPA1 currents reversibly in whole cell patch clamp experiments, indicating that under in vivo conditions, it does not react covalently, despite its potentially electrophilic ketone.
- Vallin, Karl S.A.,Sterky, Karin J.,Nyman, Eva,Bernstroem, Jenny,From, Rebecka,Linde, Christian,Minidis, Alexander B.E.,Nolting, Andreas,Naerhi, Katja,Santangelo, Ellen M.,Sehgelmeble, Fernando W.,Sohn, Daniel,Strindlund, Jennie,Weigelt, Dirk
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supporting information; experimental part
p. 5485 - 5492
(2012/09/22)
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