52688-11-6Relevant articles and documents
Development of the First Two-Pore Domain Potassium Channel TWIK-Related K+ Channel 1-Selective Agonist Possessing in Vivo Antinociceptive Activity
Vivier, Delphine,Soussia, Ismail Ben,Rodrigues, Nuno,Lolignier, Stéphane,Devilliers, Ma?ly,Chatelain, Franck C.,Prival, Laetitia,Chapuy, Eric,Bourdier, Geoffrey,Bennis, Khalil,Lesage, Florian,Eschalier, Alain,Busserolles, Jér?me,Ducki, Sylvie
supporting information, p. 1076 - 1088 (2017/02/19)
The TWIK-related K+ channel, TREK-1, has recently emerged as an attractive therapeutic target for the development of a novel class of analgesic drugs, suggesting that activation of TREK-1 could result in pain inhibition. Here, we report the synthesis of a series of substituted acrylic acids (1-54) based on our previous work with caffeate esters. The analogues were evaluated for their ability to modulate TREK-1 channel by electrophysiology and for their in vivo antinociceptive activity (acetic acid-induced writhing and hot plate assays), leading to the identification of a series of novel molecules able to activate TREK-1 and displaying potent antinociceptive activity in vivo. Furyl analogue 36 is the most promising of the series.
A new class of small molecule RNA polymerase inhibitors with activity against Rifampicin-resistant Staphylococcus aureus1
Arhin, Francis,Belanger, Odette,Ciblat, Stephane,Dehbi, Mohammed,Delorme, Daniel,Dietrich, Evelyne,Dixit, Dilip,Lafontaine, Yanick,Lehoux, Dario,Liu, Jing,McKay, Geoffrey A.,Moeck, Greg,Reddy, Ranga,Rose, Yannick,Srikumar, Ramakrishnan,Tanaka, Kelly S.E.,Williams, Daniel M.,Gros, Philippe,Pelletier, Jerry,Parr Jr., Thomas R.,Far, Adel Rafai
, p. 5812 - 5832 (2007/10/03)
The RNA polymerase holoenzyme is a proven target for antibacterial agents. A high-throughput screening program based on this enzyme from Staphylococcus aureus had previously identified a 2-ureidothiophene-3-carboxylate as a low micromolar inhibitor. An investigation of the relationships between the structures of this class of compounds and their inhibitory- and antibacterial activities is described here, leading to a set of potent RNA polymerase inhibitors with antibacterial activity. Characterization of this bioactivity, including studies of the mechanism of action, is provided, highlighting the power of the reverse chemical genetics approach in providing tools to inhibit the bacterial RNA polymerase.
