A one-pot synthesis of indole-appended heterocycles as potent anti-inflammatory, analgesic, and CNS depressant agents

Abstract

A series of novel 3-[3-(2,5-dichloro-3-thienyl)-substituted-1H-pyrazol-5-yl]-2,5-disubstituted-1H-indoles, 3-[3-(2,5-dichloro-3-thienyl)isoxazol-5-yl]-2,5-disubstituted-1H-indoles, and 4-(2,5-dichloro-3-thienyl)-6-(2,5-disubstituted-1H-indol-3-yl)-substituted pyrimidin-2(5H)-ones were synthesized by means of a one-pot reaction. Structures of all compounds were confirmed by their melting points, elemental analysis, IR, 1H NMR, 13C NMR, and mass spectral data. The novel compounds were evaluated for pharmacological studies and discussed in terms of their structural differences. Among the screened compounds, three show excellent anti-inflammatory activity with maximum inhibition (50.0-59.1 %), i.e. better than the standard drug indomethacin (50.0 %). Four of the compounds revealed highest analgesic potency. In locomotor activity, six compounds exhibited promising results for CNS depressant activity. Graphical abstract: [Figure not available: see fulltext.] © 2015 Springer-Verlag Wien.