1050443-69-0Relevant articles and documents
Synthesis and evaluation of analogues of N-phthaloyl-l-tryptophan (RG108) as inhibitors of DNA methyltransferase 1
Asgatay, Saa?dia,Champion, Christine,Marloie, Ga?l,Drujon, Thierry,Senamaud-Beaufort, Catherine,Ceccaldi, Alexandre,Erdmann, Alexandre,Rajavelu, Arumugam,Schambel, Philippe,Jeltsch, Albert,Lequin, Olivier,Karoyan, Philippe,Arimondo, Paola B.,Guianvarc'H, Dominique
, p. 421 - 434 (2014/02/14)
DNA methyltransferases (DNMT) are promising drug targets in cancer provided that new, more specific, and chemically stable inhibitors are discovered. Among the non-nucleoside DNMT inhibitors, N-phthaloyl-l-tryptophan 1 (RG108) was first identified as inhibitor of DNMT1. Here, 1 analogues were synthesized to understand its interaction with DNMT. The indole, carboxylate, and phthalimide moieties were modified. Homologated and conformationally constrained analogues were prepared. The latter were synthesized from prolinohomotryptophan derivatives through a methodology based amino-zinc-ene-enolate cyclization. All compounds were tested for their ability to inhibit DNMT1 in vitro. Among them, constrained compounds 16-18 and NPys derivatives 10-11 were found to be at least 10-fold more potent than the reference compound. The cytotoxicity on the tumor DU145 cell line of the most potent inhibitors was correlated to their inhibitory potency. Finally, docking studies were conducted in order to understand their binding mode. This study provides insights for the design of the next-generation of DNMT inhibitors.
Aminomethylation of chiral silyl enol ethers: access to β2-homotryptophane and β2-homolysine derivatives
Moumné, Roba,Larregola, Maud,Boutadla, Youcef,Lavielle, Solange,Karoyan, Philippe
, p. 4704 - 4707 (2008/09/21)
We describe here the aminomethylation of chiral silyl enol ether derivatives using iminium ion. The choice of judicious precursors with adequate protecting groups for the silylation/aminomethylation step was required to achieve the synthesis of β2-homotryptophane in few steps. The same methodology was used to prepare a β2-homolysine derivative.
