New Cytotoxic α‐Aminoacylamide and <i>bis</i>‐1,5‐Disubstituted Tetrazole Adducts From Amino‐Diterpene Molecules by Ugi Reaction

In search for new molecules of diterpene origin with promising anticancer activity, two amino-derivatives (methyl maleopimarate aminoimide and methyl 1β,13-epoxydihydroquinopimarate C4-hydrazone) were involved in the 4-component Ugi reaction (Ugi-4CR) and pseudo-7-component azido-Ugi condensation (azido-Ugi-7CR) to afford a series of adducts holding α-aminoacylamide and bis-1,5-disubstituted tetrazole substituents. The NCI-60 cancer cell panel screening revealed diterpene-type Ugi adducts 2, 5, and 6 with strong antiproliferative potency with GI₅₀ in range of 1.2-15.4 μM. The high positive correlations with standard anticancer drugs suggest microtubules or progesterone and androgen receptors as possible targets of the synthesized compounds.