Gold(I)-catalyzed cascade approach for the synthesis of tryptamine-based polycyclic privileged scaffolds as α1-adrenergic receptor antagonists

摘要

An efficient and facile gold(I)-catalyzed one-pot cascade protocol has been developed for the synthesis of tryptamine-fused polycyclic privileged structures through the treatment of substituted tryptamines and 2-ethynylbenzoic acids or 2-ethynylphenylacetic acids. This strategy features the formation of one C-C bond and two C-N bonds with high yields and broad substrate tolerance. The selected reduced target molecules are validated to perform as α_1-adrenergic receptors antagonists. The most potent one, 4bh, exhibits an IC_(50) value of 277 nM on α_(1A) subtype with a selectivity ratio of 15.8 over α_(1B) subtype.