Synthesis of novel 8-(het)aryl-6H-pyrano[4′,3′:4,5]thieno[3,2-b]pyridines by 6-endo-dig cyclization of Sonogashira products and halolactonizations with Cu salts/NXS. Preliminary antitumor evaluation

Synthesis of Novel Methyl 3-(hetero)arylthieno[3,2-b]pyridine-2-carboxylates and Antitumor Activity Evaluation: Studies In Vitro and In Ovo Grafts of Chick Chorioallantoic Membrane (CAM) with a Triple Negative Breast Cancer Cell Line

“…The precursor methyl 3-bromothieno[3,2- b ]pyridine-2-carboxylate 1 was prepared according to a known procedure, from the corresponding 3-amino compound [ 15 ] using t -BuONO and CuBr 2 [ 12 ], and it was reacted with several commercial (hetero)aryl pinacolboranes, trifluoro potassium boron salts or boronic acids under Pd-catalyzed Suzuki-Miyaura [ 8 , 16 , 17 , 18 ] cross-coupling conditions (1.2–1.6 equiv. of the boronated compound, 2–4 mol% of Pd(dppf).CH 2 Cl 2 (1:1), 6 equiv.…”

“…Since 2010, both research groups involved in this work have been interested in the synthesis and antitumor evaluation of new functionalized thieno[3,2- b ]pyridines, either on the pyridine ring by C-C Suzuki-Miyaura [ 8 ], Sonogashira [ 9 ], C-N Buchwald-Hartwig and C-O Ullmann [ 10 ] couplings, or on the thiophene by C-N coupling [ 11 ] and C-C Sonogashira followed by intramolecular cyclization [ 12 ]. Some of the compounds synthesized in the referred works showed GI 50 values below 10 µM in different human tumor cell lines and for the most promising compounds, some insights on the mechanism of action were assessed, namely, the effects in the cell cycle of NCI-H460 cells by flow cytometry and in apoptosis using Annexin(V)-PI.…”

Rhodium(III)‐Catalyzed Formal Cycloaddition between Thienopyridine/Thienopyrazine Carboxylic Acids and Alkynes, Triggered by C−H Activation

“…Thiophene fused bicyclic or tricyclic ɑ‐pyrones were earlier prepared by Pal et al [3a–c] . and Queiroz et al ., [4a,b] by reaction between ɑ‐halothiophene derivatives bearing carboxylic acids or methyl esters, and terminal alkynes, using a Pd/Cu‐catalyzed Sonogashira coupling followed by (halo)electrophilic cyclization. Using this protocol, several thiophene, [3c] benzo[ b ]thiophene derivatives, [4a] and thieno[3,2‐ b ]pyridines [4b] with promising pharmacological properties were assembled.…”

“…and Queiroz et al ., [4a,b] by reaction between ɑ‐halothiophene derivatives bearing carboxylic acids or methyl esters, and terminal alkynes, using a Pd/Cu‐catalyzed Sonogashira coupling followed by (halo)electrophilic cyclization. Using this protocol, several thiophene, [3c] benzo[ b ]thiophene derivatives, [4a] and thieno[3,2‐ b ]pyridines [4b] with promising pharmacological properties were assembled. Examples of some of these synthetic products that present antitumoral properties are shown in Figure 1 [3c,4a–b] .…”

Application of PEG400 in the one-pot synthesis of 7-[4-alkyl- or (hetero)aryl-1H-1,2,3-triazol-1-yl]thieno[3,2-b]pyridines via SNAr and Cu(I)-Catalyzed Azide-Alkyne Cycloaddition and preliminary evaluation of their anti-tumour activity

“…Since 2010 our research group has reported different Pd and/or Cu catalyzed syntheses of thieno [3,2-b]pyridine functionalized derivatives either on the pyridine ring via CAC [2,3], CAN [4], and CAO [5a,b] couplings or on the thiophene ring via CAN coupling [6], Cu(I) Azide-Alkyne Cycloaddition (CuAAC) [7], and Sonogashira coupling followed by 6-endo-dig cyclization to give the corresponding tricyclic pyranones [8]. Evaluation of the antitumour activity of the prepared compounds was performed using several human tumour cell lines and for the most promising compounds insights into their mechanisms of action were achieved (e.g.…”