Design and synthesis of 3,3′-biscoumarin-based c-Met inhibitors

Abstract

A library of biscoumarin-based c-Met inhibitors was synthesized, based on optimization of 3,3'-biscoumarin hit 3, which was identified as a non-ATP competitive inhibitor of c-Met from a diverse library of coumarin derivatives. Among these compounds, 38 and 40 not only showed potent enzyme activities with IC50 values of 107 nM and 30 nM, respectively, but also inhibited c-Met phosphorylation in BaF3/TPR-Met and EBC-1 cells.

Palladium(II)‐Catalyzed Efficient C‐3 Functionalization of Indoles with Benzylic and Allylic Alcohols under Co‐Catalyst, Acid, Base, Additive and External Ligand‐Free Conditions

“…A closely related enantioselective variant of this approach was later proposed by Trost et al using Pd 2 dba 3 ⋅CHCl 3 as the catalyst and 9‐BBN‐C 6 H 13 (105 mol%) as an additive 7c. Pullarkat et al employed a palladacycle catalyst (10 mol%) for the C‐3 allylation of 2‐substituted indoles 7d. Breit et al accomplished the allylation of indoles using the unique concept of self‐assembling palladium phosphane catalysts 7e.…”

Humic acid: A Biodegradable Organocatalyst for Solvent‐free Synthesis of Bis(indolyl)methanes, Bis(pyrazolyl)methanes, Bis‐coumarins and Bis‐lawsones

“…Dicoumarol is a normal anticoagulant and functions close to warfarin as a vitamin K antagonist. [95] Besides that, it has several biological activity such as anti-oxidants, [96] antidiabetic (α-glucosidase inhibitors), [97] anticancer, [98] antitumor, [99] antibacterial, [100] antimicrobial, [101] including enzyme inhibitors, [102] urease inhibitors, [103] HIV-1 inhibitors, [104] antiviral, [105] c-Met phosphorylation in BaF3/TPR-Met inhibitor and EBC-1 NSCLC cell lines inhibitor, [106] proliferation inhibition of K-562 [107] and also used in insecticidal, antihelminthic, phytoalexin, as reducing and stabilizing agents and ligands. [108] Several bis-coumarin analogs such as ismailin (Diospyros ismaili), dicoumarol (Melilotus alba) and gerberinol (Gerbera lanuginose) have been discovered from natural sources.…”

Fe3O4@SiO2@Im‐bisethylFc [HC2O4] as a novel recyclable heterogeneous nanocatalyst for synthesis of bis‐coumarin derivatives

“…4‐Hydroxycoumarin has become very popular due to its special properties, as well as its many biological uses, and this has led to the synthesis and identification of various derivatives of bis‐coumarin. These derivatives have been found useful in an extensive range of biological and pharmaceutical actions, including enzyme inhibitors, anticoagulants, antioxidants, antitumor drugs, anti‐diabetic (α‐glucosidase inhibitors) urease inhibitors, anticancers, antibacterials, inhibit c‐Met phosphorylation in BaF 3 /TPR‐Met and EBC‐1 NSCLC cell lines, antimicrobial, antiviral, proliferation inhibition of K‐562 and inhibit HIV‐1 . Recently, several methods have been reported for the synthesis of bis‐coumarin by the reaction of 4‐hydroxycoumarin and various aldehydes in the presence of various homogeneous and heterogeneous catalysts and under various reaction conditions, such as tetrabutylammonium bromide (TBAB), molecular iodine, [bmin] BF 4 , SO 3 H‐functionalized IL, sodium dodecyl sulfate, piperidine, n‐dodecylbenzene sulfonic acid (DBSA), [pyridin‐SO 3 H]Cl, TrBr and [Fe 3 O 4 @SiO 2 @(CH 2 ) 3 ‐Im‐SO 3 H]Cl, MNPs‐PSA and Fe 3 O 4 @SiO 2 @(CH 2 ) 3 semicarbazide‐SO 3 H/HCl .…”