Synthesis and evaluation of novel amide amino-β-lactam derivatives as cholesterol absorption inhibitors.

The β-lactam cholesterol absorption inhibitor ezetimibe is so far the only representative of this class of compounds on the market today. The goal of this work was to synthesize new amide ezetimibe analogs from trans-3-amino-(3R,4R)-β-lactam and to test their cytotoxicity and activity as cholesterol absorption inhibitors. We synthesized six new amide ezetimibe analogs.

Novel amino-β-lactam derivatives as potent cholesterol absorption inhibitors.

Two new trans-(3R,4R)-amino-β-lactam derivatives and their diastereoisomeric mixtures were synthesized as ezetimibe bioisosteres and tested in in vitro and in vivo experiments as novel β-lactam cholesterol absorption inhibitors. Both compounds exhibited low cytotoxicity in MDCKII, hNPC1L1/MDCKII, and HepG2 cell lines and potent inhibitory effect in hNPC1L1/MDCKII cells. In addition, these compounds markedly reduced cholesterol absorption in mice, resulting in reduced cholesterol concentrations in plasma, liver, and intestine.

Aminoethyl-substituted indole-3-acetic acids for the preparation of tagged and carrier-linked auxin.

Indole-3-acetic acid is an indispensable hormone (auxin) in plants and an important metabolite in humans, animals, and microorganisms. Here we introduce its 5- and 6-(2-aminoethyl)-derivatives for use in the design of novel research tools, such as immobilized and carrier-linked forms of indole-3-acetic acid and its conjugates with biochemical tags or biocompatible molecular probes. The aliphatic nitrogens of 5- and 6-(2-aminoethyl)indole were acetylated and the products were converted to the corresponding 3-(N,N-dimethylamino)methyl derivatives (gramines).