On the formation of homo‐azasteroidal esters of N,N‐bis(2‐chloroethyl)aminobenzoic acid isomers and their antitumor activity

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AbstractThe N, N‐bis(2‐chloroethyl)aminobenzoate isomers and the 4‐methyl‐3‐N, N‐bis(2‐chloro‐ethyl)aminobenzoate of 3β‐hydroxy‐13α‐amino‐13,17‐seco‐5α‐androstan‐17‐oic‐13,17‐lactam, 3α‐hydroxy‐13α‐amino‐13,17‐seco‐5α‐androstan‐17‐oic‐13,17‐lactam, 3α‐hydroxy‐13α‐amino‐13,17‐seco‐5‐androsten‐17‐oic‐13,17‐lactam and 17β‐hydroxy‐3‐aza‐A‐homo‐4α‐androsten‐4‐one, have been prepared and their biological activity evaluated against P388 leukemia in vivo and Ehrlich Ascites 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 leukemia, while compounds 1, 4, 6, 13, 14 and the alkylating congeners 17, 18 and 20 are active. The effect of the homo‐azasteroidal of N, N‐bis(2‐chloroethyl)aminobenzoic acid isomers and of 4‐methyl‐3‐N, N‐bis(2‐chloroethyl)aminobenzoic acid on the incorporation of the radioactive precursor into the DNA of L1210, P388 leukemias, Ehrlich ascites tumor and, baby Hamster kidney cells was investigated. Higher inhibitory effects on the incorporation of the radioactive precursor was obtained with the ortho derivatives, yielding <70% inhibition of thymidine incorporation in all tumor lines tested.