José Carlos Menéndez

Inhibitors of multidrug resistance to antitumor agents (MDR).

Multidrug resistance is one of the main obstacles in the chemotherapy of cancer. Its inhibition by combination of chemosensitizers with antitumor compounds is a very active field of research, since safe and potent reversal agents would be beneficial for clinical use. Most modulators act by binding to membrane transport proteins (specially P-gp and MRP) and inhibiting their drug-effluxing activity, or by indirect mechanisms related to phosphorylation of the transport proteins or expression of the mdr1 and mrp1 genes. The main body of the review focuses on the study of the known MDR modulators, which are classified according to their chemical structures. General structure-activity studies of this therapeutic group are hampered by the very heterogeneous chemical structure of the compounds, although some conclusions have been drawn from the study of homogeneous series of molecules.

Synthesis of 2,5,8(1H)-Quinolinetrione Derivatives through Vilsmeier-Haack Formylatioin of 2,5-Dimethoxyanilides

The preparation of 2,5,8(1H)-quinolinetrione derivatives bearing both electron-withdrawing and electron-releasing groups at C 3 is described. The reaction sequence employed involves Vilsmeier-Haack cyclization of 2,5-dimethoxyanilides into 3-substituted 5,8-dimethoxy-2-chloroquinolines, followed by hydrolysis to the corresponding 2(1H)-quinolinones and oxidative demethylation with cerium ammonium nitrate

A Friedländer approach to 3-substituted 2,5,8-(1H)-quinolinetriones

An efficient method is proposed for the preparation of 3-substituted carbostyrilquinone derivatives, based on Friedlander synthesis of the 5,8-dialkoxyquinolines followed by cerium ammonium nitrate oxidative demethylation