ON THE FORMATION OF HOMO-AZASTEROIDAL ESTERS OF N,N-BIS(2-CHLOROETHYL)AMINOBENZOIC ACID ISOMERS AND THEIR ANTITUMOR-ACTIVITY

The N,N-bis(2-chloroethyl)aminobenzoate isomers and the 4-methyl-3-N,N -bis(2-chloroethyl)aminobenzoate of o-13,17-seco-5alpha-androstan-17-o ic-13,17-lactam, o-13,17-seco-5alpha-androstan-17-oic-13,17-lactam, a- amino-13,17-seco-5-androsten-17-oic-13,17-lactam and 7beta-hydroxy-3-a za-A-homo-4alpha-androsten-4-one, have been prepared and their biologi cal activity evaluated against P388 leukemia in vivo and Ehrlich Ascit es tumor (EAT), P388 and L1210 leukemias and Baby Hamster cells (BHK) in vitro. The esters in which the alkylating congener is linked to the lactam alcohol in the axial position are inactive in vivo in P388 leu kemia, while compounds 1, 4, 6, 13, 14 and the alkylating congeners 17 , 18 and 20 are active. The effect of the homoazasteroidal of N,N-bis( 2-chloroethyl)aminobenzoic acid isomers and of 4-methyl-3-N,N-bis(2-ch loroethyl)aminobenzoic acid on the incorporation of the radioactive pr ecursor into the DNA of L1210, P388 leukemias, Ehrlich ascites tumor a nd, baby Hamster kidney cells was investigated. Higher inhibitory effe cts on the incorporation of the radioactive precursor was obtained wit h the ortho derivatives, yielding >70% inhibition of thymidine incorpo ration in all tumor lines tested.