Synthesis and COX-2 Inhibitory Activities of Rutaecarpine Homologues

A series of rutaecarpine homologues were prepared from 2,3-polymethylene-4(3H-quinazolinones in 4 steps [i) PhCHO/Ac$_2$O, ⅱ) O,$_3$ ⅲ) PhNHNH$_2$HCl, and ⅳ) PPA], in which dihedral angles of the two planar aromatic rings (indole and 4(3H)-quinazolinone) were controlled in a regular fashion. Their inhibitory activities on COX-1 and COX-2 were evaluated to show that the inhibitory activities were increased with the increase of the length of methylene unit while selectivities on COX-2 decreased leading a loss in trimethylene bridged system.