Tetracyclic spirooxindole blockers of hNaV1.7: activity in vitro and in CFA-induced inflammatory pain model

The discovery of oxazolones-grafted spirooxindoles via three-component diversity oriented synthesis and their preliminary biological evaluation

“…[2] For example, the spirooxindole core is a privileged heterocyclic ring system, which constitutes the core structural element of pharmaceutically relevant natural products. [3,4] The natural spirotryprostatin A and its related alkaloids which have been identified as novel inhibitors of microtubule assembly, have encouraged the design and synthesis of novel spirocyclic oxindoles exhibiting a wide spectrum of important bioactivities such as antitumor [5], antimycobacterial [6], anti-inflammatory [7] and antitubercular [8] properties (Figure 1a). Though these biologically active heterocycles have already been synthesized by total synthesis, the targeted drug discovery process toward natural products is always tedious.…”

Synthesis of Hexahydrospiro[pyrazolo[3,4‐b]quinoline‐4,1′‐pyrrolo[3,2,1‐ij]quinoline‐2′,5(1H,4′H)‐diones] from 5,6‐dihydro‐4H‐pyrrolo[3,2,1‐ij]quinoline‐1,2‐dione Using Fe3O4@Cu(OH)x as a Nanocatalyst

“…Such structures have prompted cutting‐edge total syntheses, for example, of structurally complex alkaloids (e.g., horsfiline and welwitindolinone A ). Compounds with diverse medicinal interests are other examples containing spiro[3,3′‐oxindoles] moieties: broad‐spectrum anticancer potency , relief of inflammatory pain , antimicrobial activity , inhibitors of the dengue virus , and of the influenza virus . Natural products, too, show medicinal potential, for example, thiopyran‐spirooxindoles isolated from Isatis indigotica have activity against the influenza virus .…”

Spiro[4H‐2,3‐dihydropyran‐3,3′‐oxindoles] derived from 1,2,3,4‐tetrahydroquinoline

“…Interest in spiro‐oxindoles, that is, compounds 1 having an oxindole (1,3‐dihydro‐2 H ‐indol‐2‐one) nucleus but with a spirocyclic ring fused at C‐3, has been considerable, as one may judge from a comprehensive review on “Recent progress on routes to spirooxindole systems derived from isatin” in this journal, a Tetrahedron Report on “Recent advances in the synthesis of biologically active spirooxindoles”, and a mini review on “Pyrrolidinyl‐spiro‐oxindole natural products as inspirations for the development of potential therapeutic agents” and with more than 30 relevant papers at the time of writing in 2017, including a review on “Recent applications of isatin in the synthesis of organic compounds” . Various aspects of compounds with general structure 6 have caused this interest: the cutting‐edge total synthesis of complex spiro‐oxindole alkaloids such as horsfiline or welwitindolinone A and the synthesis of substances with diverse medicinal potentials, for example broad‐spectrum anticancer potency , antitumor effects on melanoma , relief of inflammatory pain , or having antimicrobial activity .…”