Phenyl N-mustard linked to DNA-affinic molecules or water-soluble aryl rings, method and their use as cancer therapeutic agents
The present disclosure relates to new DNA-directed alkylating agents and water-soluble N-mustard agents with improved chemical stability and anti-tumor therapeutic efficacy.
1. The compound selected from the group consisting of
2. The compound of Formula (I-C):
or a 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—;
Z′ is —NH, —NHNH, —OCH 2 —, or —O—;
—NHC(O)R is at the meta or para position corresponding to Z′;
R is selected from optionally substituted C 1 -C 6 alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted heterocyclyl and optionally substituted aryl.
3. The compound of claim 2 , wherein X and Y are the same.
4. The compound of claim 3 , wherein X and Y are Cl.
5. The compound of claim 2 , wherein Z is —NH.
6. The compound of claim 2 , wherein Z′ is —NH.
7. The compound of claim 2 , wherein R is —(CH 2 )nNR 1 R 2 , and n is 1 to 6.
8. The compound of claim 7 , wherein R 1 and R 2 are the same or independently C 1 -C 6 alkyl.
9. The compound of claim 7 , wherein NR 1 R 2 is a cyclic amine.
10. The compound of claim 9 , wherein NR 1 R 2 is selected from the group consisting of morpholine, pyrrolidine, piperidine, 1-methylpiperazine and 4-piperidinopiperidine.
11. The compound of claim 2 , wherein the compound is selected from the group consisting of
12. The compound having the formula:
13. The compound of claim 2 , wherein the compound is