Discovery of indolizines containing triazine moiety as new leads for the development of antitumoral agents targeting mitotic events

Exploring isoxazoles and pyrrolidinones decorated with the 4,6‐dimethoxy‐1,3,5‐triazine unit as human farnesyltransferase inhibitors

“…The literature devoted to 2‐ethynyl‐4,6‐dimethoxy‐1,3,5‐triazine 1 is extremely scarce . We have recently proved that this dipolarophile constitutes a valuable intermediate in the synthesis of molecules with biological potential . From a synthetic point of view, alkyne 1 is also interesting since the dimethoxytriazine unit has a very pronounced electro‐withdrawing effect and should behave in the same way as classical methyl or ethyl propiolates in cycloaddition reactions.…”

Insights on the Chemical Behavior of Ethyl Cyanoformate: Dipolarophile, Cyano or Ethoxycarbonyl Source

“…Cycloimmonium salts 4 a‐g and 4 i‐n were obtained as bromides while the 4‐cyanopyridinium salt 4 h was obtained as a chloride. 3,5‐Difluoropyridinium 4 a and 3,5‐dichloropyridinium 4 b salts are not yet described in the literature, while the other intermediate salts 4 c‐n have already been reported …”

“…Compound D ) have already been reported as human Polo‐like kinase 1 (PLK1) inhibitors (Figure ). We recently submitted compound E to the NCI cancer screening test and highlighted interesting activities against some cancer cell lines such as SNB‐75 (CNS cancer), 786–0 and RXF 393 (renal cancer) . The standard NCI Compare results indicated that indolizine E may target PLK1 .…”

“…We recently submitted compound E to the NCI cancer screening test and highlighted interesting activities against some cancer cell lines such as SNB‐75 (CNS cancer), 786–0 and RXF 393 (renal cancer) . The standard NCI Compare results indicated that indolizine E may target PLK1 . The indolizine unit was also successfully used as the B‐ring of tubulin polymerization inhibitors, potent antitumor agents .…”

“…The indolizine unit was also successfully used as the B‐ring of tubulin polymerization inhibitors, potent antitumor agents . Moreover, indolizine derivatives are easily synthesized by [3 + 2] cycloaddition reaction of the ylide generated in situ by base treatment of pyridinium salts with dipolarophiles such as ethyl propiolate, acrylonitrile, 2‐ethynyl‐4,6‐dimethoxy‐1,3,5‐triazine, dimethyl or diethyl acetylenedicarboxylate, followed by spontaneous aromatization of intermediates . Given the pharmacological properties reported for (aza)indolizine derivatives and our interest to seek for unprecedented biologically active indolizine derivatives the synthesis of new imidazo‐pyridines 1 was envisaged (Figure ).…”