Inhibition of NaV1.6 sodium channel currents by a novel series of 1,4-disubstituted-triazole derivatives obtained via copper-catalyzed click chemistry.
Inhibition of NaV1.6 sodium channel currents by a novel series of 1,4-disubstituted-triazole derivatives obtained via copper-catalyzed click chemistry.
复制标题
DOI：
10.1016/j.bmcl.2012.08.067
复制
发表时间：
2012-10-15
影响因子：
2.7
通讯作者：
Zuliani, Valentina
中科院分区：
文献类型：
--
作者：
Rivara, Mirko;Patel, Manoj K.;Amori, Laura;Zuliani, Valentina
We have synthesized and evaluated a series of 1,4-disubstituted-triazole derivatives for inhibition of the rat NaV1.6 sodium channel isoform, an isoform thought to play an important role in controlling neuronal firing. Starting from a series of 2,4(1H)-diarylimidazoles previously published, we decided to extend the SAR study by replacing the imidazole with a different heterocyclic scaffold and by varying the aryl substituents on the central aromatic ring. The 1,4-disubstituted 1,2,3-triazoles were prepared employing the copper-catalyzed azide-alkyne cycloaddition (CuAAC). Many of the new molecules were able to block the rNav1.6 currents at 10 µM by over 20%, displaying IC50 values ranging in the low micromolar, thus indicating that triazole can efficiently replace the central heterocyclic core. Moreover, the introduction of a long chain at C4 of the central triazole seems beneficial for increased rNav1.6 current block, whereas the length of N1 substituent seems less crucial for inhibition, as long as a phenyl ring is not direcly connected to the triazole. These results provide additional information on the structural features necessary for block of the voltage-gated sodium channels. These new data will be exploited in the preparation of new compounds and could result in potentially useful AEDs.
登录
查看更多内容
影响因子：
7.3
作者：
MICETICH, RG;MAITI, SN;OGAWA, K
通讯作者：
OGAWA, K
影响因子：
2.7
作者：
Rivara, Mirko;Baheti, Aparna R.;Zuliani, Valentina
通讯作者：
Zuliani, Valentina
影响因子：
5.3
作者：
Van Wart, Audra;Matthews, Gary
通讯作者：
Matthews, Gary
影响因子：
6.1
作者：
Hargus, Nicholas J.;Merrick, Ellen C.;Nigam, Aradhya;Kalmar, Christopher L.;Baheti, Aparna R.;Bertram, Edward H., III;Patel, Manoj K.
通讯作者：
Patel, Manoj K.
影响因子：
3.5
作者：
Martin, Melinda S.;Tang, Bin;Escayg, Andrew
通讯作者：
Escayg, Andrew