New alkylating agents: butyrophenone derivatives

The antimitotic properties associated with the bis (2-chloroethyl) amino group are well known, a number of compounds bearing this group being of therapeutic interest. The choice of a suitable supporting moiety for this group is important. Our experiments on a butyrophenone derivative, ketocaine, which possesses local anesthetic activity, showed that this drug is able to modify the oxygen consumption by tissues with prevailing anaerobic metabolism and to inhibit the mitotic activity of human lymphocytes in culture stimulated by phytohemagglutinin. These observations prompted us to prepare compounds by the general formula reported in Tables I and II. All compounds were tested in mice implanted i.p. with 10(6) Ehrlich ascites tumour cells. After 24 h the animals were treated with a single dose of the compound. The antitumor activity was correlated with: position (2, 4) and length (n = 0-2) of the chain with carbonyl group; presence (R' = H, ND2) and position (2, 4) of nitro group; monofunzional or bifunzional compound. Some of these show a potent antitumor activity.