Synthesis and bioevaluation of a series of alkyl ethers of p-N,N-bis(2-chloroethyl)aminophenol

A series of even numbered normal alkyl ethers (C2-C14) of p-N,N-bis(2-chloroethyl)aminophenol were synthesized and evaluated as to acute toxicity in mice and effects on survival in L-1210 leukemic mice. All of the ether derivatives demonstrated significantly lower acute toxicity than the parent phenol mustard. Significant survival times (greater than or equal to 125%) were obtained with all compounds except the hexyl derivative. The decyl ether produced the greatest significant increase and the ethyl ether the lowest significant increase in mean survival time. Significant survival times were produced at four dosage levels for the butyl, decyl, and dodecyl derivatives, three dosage levels for the octyl and tetradecyl derivatives, and one dosage level for the ethyl derivative.