No abstract

Lysyl oxidase (LOX) is a secreted copper-dependent amine oxidase that cross-links collagens and elastin in the extracellular matrix and is a critical mediator of tumor growth and metastatic spread. LOX is a target for cancer therapy, and thus the search for therapeutic agents against LOX has been widely sought. We report herein the medicinal chemistry discovery of a series of LOX inhibitors bearing an aminomethylenethiophene (AMT) scaffold. High-throughput screening provided the initial hits. Structure–activity relationship (SAR) studies led to the discovery of AMT inhibitors with sub-micromolar half-maximal inhibitory concentrations (IC50) in a LOX enzyme activity assay. Further SAR optimization yielded the orally bioavailable LOX inhibitor CCT365623 with good anti-LOX potency, selectivity, pharmacokinetic properties, as well as anti-metastatic efficacy.

We describe three cases that presented with symptoms suggestive of appendicitis but were found at operation to have an inflamed solitary caecal diverticulum. All were treated successfully with diverticulectomy or inversion of the diverticulum. We wish to highlight this diagnosis and its surgical management so that informed decisions can be made if this is first encountered in the operating theatre.

Vicinal diamines constitute one the most important functional motif in organic chemistry because of its wide occurrence in a variety of biological and pharmaceutical molecules. We report an efficient metal‐free, highly stereoselective intramolecular diamination using a novel chiral hypervalent iodine reagent together with its application as an efficient catalyst for the synthesis of diamines.