Design, synthesis and antiarrhythmic activity of new amide derivatives of indole-3-carboxylic acid

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Resumo

The hERG (human ether-à-go-go-related gene) potassium channel has elicited intense scientific interest due to its counter-intuitive kinetics and its association with arrhythmia and sudden death. Kv1.5 potassium channel, encoded by KCNA5, is a promising target for the treatment of atrial fibrillation, one of the common arrhythmia. A new indole derivatives were synthesized via reaction of indole-3-carboxylic acid with 4-[2-(diethylamino)ethoxy]aniline under peptide coupling protocol in DMF with good yields and evaluated their antiarrythmic activity. Among them, 2-butyl- N -{4-[2-(diethylamino)ethoxy]phenyl}-1-(2-fluorobenzoyl)-1 H -indole-3-carboxamide 34 showed preferable anti-arrhythmic effects and favoured safety. These results indicate that lead compound can be a promising antiarrythmic drug for further studies.

Sobre autores

Ya. Platonova

Lomonosov Moscow State University

Email: knoposk@gmail.com

Z. Tarasov

Lomonosov Moscow State University

A. Volov

Lomonosov Moscow State University

N. Volov

Pirogov Russian National Research Medical University

S. Savilov

Lomonosov Moscow State University;Kurnakov Institute of General and Inorganic Chemistry, Russian Academy of Sciences

Bibliografia

  1. Burashnikov A., Antzelevitch C. Heart Rhythm. 2008, 5, 1304-1309. doi: 10.1016/j.hrthm.2008.05.020
  2. Mulder B.A., Schnabel R.B., Rienstra M. Eur. J. Heart Failure. 2013, 15, 366-367. doi: 10.1093/eurjhf/hft039
  3. Nattel S., Carlsson L. Nature. Rev. Drug Discovery. 2006, 5, 1034-1049. doi: 10.1038/nrd2112
  4. Wolf P.A., Mitchell J.B., Baker C.S., Kannel W.B., D'Agostino R.B. Arch. Intern. Med. 1998, 158, 229-234. doi: 10.1001/archinte.158.3.229
  5. Brandt M.C., Priebe L., Bohle T., Sudkamp M., Beuckelmann D.J. J. Mol. Cell. Cardiol. 2000, 32, 1885-1896. doi: 10.1006/jmcc.2000.1221
  6. Brunner M., Kodirov S.A., Mitchell G.F., Buckett P.D., Shibata K., Folco E.J., Baker L., Salama G., Chan D.P., Zhou J., Koren G. Am. J. Physiol. Heart. Circ. Physiol. 2003, 285, H194-H203. doi: 10.1152/ajpheart.00971.2002
  7. Yang Y., Li J., Lin X., Lin X., Yang Y., Hong K., Wang L., Liu J., Li L., Yan D., Liang D., Xiao J., Jin H., Wu J., Zhang Y., Chen Y.-H. J. Hum. Genet. 2009, 54, 277-283. doi: 10.1038/jhg.2009.26
  8. Olson T.M., Alekseev A.E., Liu X.K., Park S., Zingman L.V., Bienengraeber M., Sattiraju S., Ballew J.D., Jahangir A., Terzic A. Hum. Mol. Genet. 2006, 15, 2185-2191. doi: 10.1093/hmg/ddl143
  9. Wang Y.J., Chen B.S., Lin M.W., Lin A.A., Peng H., Sung R.J., Wu S.N. Toxicol. Sci. 2008, 106, 454-463. doi: 10.1093/toxsci/kfn189
  10. Nerbonne J.M., Kass R.S. Physiol. Rev. 2005, 85, 1205-1253. doi: 10.1152/physrev.00002.2005
  11. Martens J.R., Kwak Y.G., Tamkun M.M. Trends. Cardiovas. Med. 1999, 9, 253-258. doi: 10.1016/s1050-1738(00)00037-2
  12. Tanabe Y., Hatada K., Naito N., Aizawa Y., Chinushi M., Nawa H., Aizawa Y. Biochem. Biophys. Res. Commun. 2006, 345, 1116-1121. doi: 10.1016/j.bbrc.2006.05.030.
  13. Wu S., Fluxe A., Sheffer J., Janusz J.M., Blass B.E., White R., Jackson C., Hedges R., Murawsky M., Fang B., Fadayel G.M., Hare M., Djandjighian L. Bioorg. Med. Chem. Lett. 2006, 16, 6213-6218. doi: 10.1016/j.bmcl.2006.09.021
  14. Griffin A., Scott R.H. Resp. Physiol. 1994, 96, 297-309. doi: 10.1016/0034-5687(94)90134-1
  15. Rettig J., Heinemann S.H., Wunder F., Lorra C., Parcej D.N., Dolly J.O., Pongs O. Nature. 1994, 369, 289-294. doi: 10.1038/369289a0
  16. Herre J.M., Sauve M.J., Malone P., Griffin J.C., Helmy I., Langberg J.J., Goldberg H., Scheinmann M.M. J. Am. Coll. Cardiol. 1989, 13, 442. doi: 10.1016/0735-1097(89)90525-1
  17. Carlsson B., Singh B.N., Temciuc M., Nilsson S., Li Y.-L., Mellin C., Malm J. J. Med. Chem. 2002, 45, 623-630. doi: 10.1021/jm001126+
  18. Druzgala P., Milner P.G. Пат. US 2002/0193428A1. США.
  19. Golightly L.K., Pharm D. Pharmacotherapy. 1982, 2, 134-147.
  20. Aelig W.H. Am. Heart. J. 1982, 104, 346-356.
  21. Nikhar S., Siokas I., Schlicher L., Lee S., Gyrd-Hansen M., Degterev A., Cuny G.D. Eur. J. Med. Chem. 2021, 215, 113252. doi: 10.1016/j.ejmech.2021.113252

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