Yantai Institute of Materia Medica

A new series of 1H-pyrrolo[3,2-c]pyridine derivatives were designed and synthesised as colchicine-binding site inhibitors. Preliminary biological evaluations showed that most of the target compounds displayed moderate to excellent antitumor activities against three cancer cell lines (HeLa, SGC-7901, and MCF-7) in vitro. Among them, 10t exhibited the most potent activities against three cancer cell lines with IC₅₀ values ranging from 0.12 to 0.21 μM. Tubulin polymerisation experiments indicated that 10t potently inhibited tubulin polymerisation at concentrations of 3 μM and 5 μM, and immunostaining assays revealed that 10t remarkably disrupted tubulin microtubule dynamics at a concentration of 0.12 μM. Furthermore, cell cycle studies and cell apoptosis analyses demonstrated that 10t at concentrations of 0.12 μM, 0.24 μM, and 0.36 μM significantly caused G2/M phase cell cycle arrest and apoptosis. The results of molecular modelling studies suggested that 10t interacts with tubulin by forming hydrogen bonds with colchicine sites Thrα179 and Asnβ349. In addition, the prediction of physicochemical properties disclosed that 10t conformed well to the Lipinski's rule of five.

MB-07344 was found to be a very potent liver-selective phosphonic acid thyroid hormone receptor (TR) agonist.Few routes have been reported for the synthesis of MB-07344.In one route reported by Boyer and colleagues, 2-isopropylphenol was brominated and subsequently protected by chloromethyl Me ether (MOMCl).MOMCl is a toxic and carcinogenic compound, unfriendly to both people and the environment and at the deprotection step it requires acid or heat.These considerations have limited its use for the desired purpose.In the present work, we describe a novel and practical method to synthesize MB-07344.Reduction of compound {4-[(4-Benzyloxy-3-isopropylphenyl)hydroxymethyl]-3,5-dimethylphenoxymethyl}-phosphonic acid dibenzyl ester using hydrogen in the presence of palladium leads to MB-07344.This method does not require the use of MOMCl and TMSBr, which are inconvenient to use in both the academic laboratory and in industry.

Herein we report a concise and efficient method for the synthesis of spirocyclic oxindole scaffolds via the formal [4+1] cycloaddition of 3-chlorooxindoles with o-quinone methides (o-QMs).In this method, using NaOH as the base ensures that the one-pot domino reaction occurs under mild reaction conditions, with no heating under an operationally simple procedure, affording the desired 3,2'-tetrahy-drofuryl-spirooxindoles in high yields and moderate diastereoselectivities.