POTENTIAL ANTILEUKEMIC AND IMMUNOSUPPRESSIVE DRUGS . PREPARATION AND IN VITRO PHARMACOLOGICAL ACTIVITY OF SOME BENZO-2,1,3-OXADIAZOLES (BENZOFURAZANS) AND THEIR N-OXIDES (BENZOFUROXANS)

Eight methods for synthesizing various benzo-2,1,3-oxadiazoles (benzofurazans) and their N-oxides (benzofuroxans) are described. The activity of benzofurazans and benzofuroxans as in vitro inhibitors of RNA synthesis in sheep lymphocytes is given. Optimal drug activity in vitro was exhibited by 4-nitrobenzofurazan and 4-nitrobenzofuroxan and their 7-thio or 7-phenoxy derivatives. These compounds readily formed Meisenheimer complexes with nucleophiles and their drug action was abolished by preincubation with aliphatic thiols, e.g., glutathione. It is concluded that the most active compounds reacted with key intracellular thiol groups. The 4-nitro group and furazan ring were essential for optimal drug activity. © 1968, American Chemical Society. All rights reserved.