Synthesis and biological evaluation of A-ring biaryl-carbamate analogues of rhazinilam.
An improvement of the synthesis of biphenyl-carbamate 2a, the most active analogue of rhazinilam 1 so far, was performed using the Pd-catalyzed borylation/Suzuki coupling (BSC) method developed in our laboratories. The preparation of A-ring analogues of 2a bearing electron-withdrawing or donating groups is reported according to this new synthetic scheme. The antitubulin properties as well as the cytotoxicity of these compounds toward human cancer cell lines were evaluated in comparison with rhazinilam and 2a.
Baudoin
Olivier
O
Institut de Chimie des Substances Naturelles, CNRS, avenue de la Terrasse, Gif-sur-Yvette, France. baudoin@icsn.cnrs-gif.fr
Claveau
Fabien
F
Thoret
Sylviane
S
Herrbach
Audrey
A
Guénard
Daniel
D
Guéritte
Françoise
F
D000470:Alkaloids / Q000138:chemical synthesis* / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D002384:Catalysis; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007202:Indicators and Reagents; D007212:Indolizines; D007769:Lactams; D008870:Microtubules / Q000187:drug effects; D010165:Palladium; D014407:Tumor Cells, Cultured
D000470:Alkaloids; D000970:Antineoplastic Agents; D007202:Indicators and Reagents; D007212:Indolizines; D007769:Lactams; C009170:rhazinilam; D010165:Palladium