Indole-like Trk receptor antagonists

Tammiku-Taul, J.; Park, R.; Jaanson, K.; Luberg, K.; Dobchev, D. A.; Kananovich, D.; Noole, A.; Mandel, M.; Kaasik, A.; Lopp, M.; Timmusk, T.; Karelson, M. (2016). Indole-like Trk receptor antagonists. European Journal of Medicinal Chemistry, 121, 541−552.10.1016/j.ejmech.2016.06.003.
ajakirjaartikkel
Tammiku-Taul, J.; Park, R.; Jaanson, K.; Luberg, K.; Dobchev, D. A.; Kananovich, D.; Noole, A.; Mandel, M.; Kaasik, A.; Lopp, M.; Timmusk, T.; Karelson, M.
  • Inglise
European Journal of Medicinal Chemistry
121
2016
541552
Ilmunud
1.1. Teadusartiklid, mis on kajastatud Web of Science andmebaasides Science Citation Index Expanded, Social Sciences Citation Index, Arts & Humanities Citation Index ja/või andmebaasis Scopus (v.a. kogumikud)
WOS

Viited terviktekstile

dx.doi.org/10.1016/j.ejmech.2016.06.003

Lisainfo

Article The virtual screening for new scaffolds for TrkA receptor antagonists resulted in potential low molecular weight drug candidates for the treatment of neuropathic pain and cancer. In particular, the compound (Z)-3-((5-methoxy-1H-indol-3-yl)methylene)-2-oxindole and its derivatives were assessed for their inhibitory activity against Trk receptors. The IC50 values were computationally predicted in combination of molecular and fragment-based QSAR. Thereafter, based on the structure-activity relationships (SAR), a series of new compounds were designed and synthesized. Among the final selection of 13 compounds, (Z)-3-((5-methoxy-1-methyl-1H-indol-3-yl)methylene)-N-methyl-2-oxindole-5-sulfonamide showed the best TrkA inhibitory activity using both biochemical and cellular assays and (Z)-3-((5-methoxy-1-methyl-1H-indol-3-yl)methylene)-2-oxindole-5-sulfonamide was the most potent inhibitor of TrkB and TrkC.
TrkA; TrkB; Antagonist; Fragment-based QSAR; 2-Oxindole