Piperidine-catalyzed synthesis of (<i>E</i>)-2-cyanoacrylamides: crystallographic, antiproliferative, and docking studies.

ABSTRACT: A piperidine-catalyzed Knoevenagel condensation between (hetero)aromatic aldehydes 1a-i and 2-cyanoacetamide 2a was developed to afford (E)-2-cyano-3-(het)arylacrylamides 3a-i in 40-95% yields under mild and environmentally friendly conditions. The methodology was further extended to other methylene active compounds, including malonamide 2b and ethyl cyanoacetate 2c, providing the corresponding adducts 3m-o in 54-81% yields. The (E)-stereochemistry of 3-arylacrylamide 3i was unambiguously confirmed by single-crystal X-ray diffraction analysis. The antiproliferative activity of compounds 3a-o was evaluated across the NCI-60 human cancer cell line panel. Compounds 3f and 3o exhibited the highest potency against the CAKI-1 renal cancer cell line, with GI₅₀ values of 0

SUBMITTER: Serrano-Sterling C 

PROVIDER: S-EPMC12757768 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature