Aniline or phenol mustards linked to DNA-affinic molecules or water-soluble aromatic rings and their use as cancer therapeutic agents
New aniline or phenol N-mustards linked to DNA-affinity carriers (such as 9-anilinoacridines, acridines and quinolines), aminobenzamides or aminophenol ethers by a urea, carbamic acid, carbanic acid ester, hydrazineurea, hydrazinecarbamic acid ester, phenoxyurea, phenoxycarbamic acid ester linkage with improved chemical stability and anti-tumor therapeutic efficacy are provided.
1. A compound of the following Formula VIII or salt thereof:
Wherein X and Y are independently selected from the group consisting of Cl, Br, I and OSO 2 Me.
Z is NH or O;
and wherein R is (CH 2 ) n NR 1 R 2 , (CH 2 ) n CH(OH)CH 2 OH, (CH 2 ) n —N-morpholine, piperidine, 4-piperidinopiperidine, or morpholine;
R 1 and R 2 are each independently C 1 -C 6 alkyl; and
n is 1-5.
2. The compound of claim 1 wherein R is (CH 2 ) n NR 1 R 2 , and the compound is a salt formed with an acid.
3. The compound of claim 2 wherein the acid is selected from the group consisting of HCl, HBr, H 1 , H 2 SO 4 , HCOOH, CH 3 COOH, citric acid, oxalic acid, and tartaric acid.
4. The compound of claim 1 being 3-(3-{4-[bis-(2-chloroethyl)amino]phenyl}-ureido)-N-(2-dimethylaminoethyl)benzamide hydrochloride (23, BO-1055).