PRECLINICAL ANTITUMOR EFFICACY OF ANALOGS OF XK469 - -[4-(7-CHLORO-2-QUINOXALINYLOXY)PHENOXY]PROPIONATE

A series of quinoxaline analogs of the herbicide Assure(R) was found t o have selective cytotoxicity for solid tumors of mice in a disk-diffu sion-soft-agar-colony-formation-assay compared to L1210 leukemia. Four agents without selective cytotoxicity and 14 agents with selective cy totoxicity were evaluated in vivo for activity against a solid tumor. The four agents without selective cytotoxicity in the disk-assay were inactive in vivo (T/C > 42%). Thirteen of the fourteen agents with sel ectivity in the disk-assay were active in vivo (T/C < 42%). Five of th e agents had curative activity. These five agents had a halogen (F, Cl , Br) in the 7-position (whereas Assure(R) had a Cl in the 6 position) . All agents with curative activity were either a carboxylic acid, or a derivative thereof, whereas Assure(R) is the ethyl ester of the carb oxylic acid. All other structural features were identical between Assu re(R) and the curative agents. Assure(R) had no selective cytotoxicity for solid tumors in the disk-assay, and was devoid of antitumor activ ity. The analog XK469 is in clinical development.