Tubulin-binding dibenz[c,e]oxepines as colchinol analogues for targeting tumour vasculature

Abstract

Various methoxy- and hydroxy-substituted dibenz[c,e]oxepines were prepared via the copper(I)-induced coupling of ether-tethered arylstannanes or the dehydrative cyclisation of 1,1'-biphenyl-2,2'-dimethanols, assembled using the Ullmann cross-coupling of ortho-bromoaryl carbonyl compounds. The dibenzoxepines were screened for their ability to inhibit tubulin polymerisation and the in vitro growth of K562 human chronic myelogenous leukemia cells. The most active was 5,7-dihydro-3,9,10,11-tetramethoxydibenz[c,e]oxepin-4-ol, whose tubulin inhibitory and cytotoxicity (IC(50)) values were 1 μM and 40 nM, respectively.

Exciting progress in the transition metal‐catalyzed synthesis of oxepines, benzoxepines, dibenzoxepines, and other derivatives

“…In 2011, Edwards et al synthesize a library of methoxy‐ and hydroxy‐substituted dibenzo[ c , e ]oxepines 155 through the Cu‐catalyzed intramolecular coupling reaction of ether‐tethered arylstannanes (Scheme 45), or the Ullmann cross‐coupling of ortho ‐bromoaryl carbonyl compounds followed the dehydrative cyclization of resulted 1,1′‐biphenyl‐2,2′‐dimethanols (Scheme 46). [ 83 ]…”

A Tandem Sulfonylation and Knoevenagel Condensation for the Preparation of Sulfocoumarin-3-carboxylates

“…9 These two methods are mainly restricted by the inconvenient routes to access the sulfonyl reagents. In 2012, in response to the irreproducibility of literature procedures, 10 Zalubovskis et al developed an efficient procedure to prepare 3, 4- featured the mesylation of salicylaldehydes, a DBU-catalyzed aldol-type condensation, and POCl 3 -mediated dehydration (Scheme 1c). 11 This method was widely used in the studies by Supuran and co-workers on the bioactivities of structurally diverse sulfocoumarins.…”

Crystal structures of methyl 3-phenyl-4,5-dihydro-1H,3H-benzo[4,5]imidazo[2,1-c][1,4]oxazepine-4-carboxylate and methyl 1-methyl-3-phenyl-4,5-dihydro-1H,3H-benzo[4,5]imidazo[2,1-c][1,4]oxazepine-4-carboxylate

“…Tumor growth requires the support of an associated blood supply, making tumor vasculature a potential target for anticancer therapy. This principle has inspired decades of research into the pathways of angiogenesis (the formation of new blood vessels), leading to the identification of a family of vascular endothelial growth factors (VEGFs) that stimulate this process (Edwards et al, 2011). Sevenmembered oxygen heterocycles are ubiquitous in natural products and show a wide spectrum of biological activity (Bera et al, 2014).…”