Etoposide analogs and methods of use thereof
View Patent ↗Etoposide analogs such as 4′-O-demethyl-4β-[4″-(methyl-L-tyrosine-N-carbonyl)-anilino]-4-desoxy-podophyllotoxin (12) and 4′-O-demethyl-4β-[4″-(methyl-L-tryptophan-N-carbonyl)-anilino]-4-desoxypodophyllotoxin (13) are described, along with pharmaceutical formulations containing the same, methods of use thereof, and intermediates and methods of making the same.
1. A compound having the formula:
wherein:
X is a linking group selected from the group consisting of —CH═N— and —CH 2 NH—; and
D is selected from the group consisting of —CH 2 OC(═CH 2 )—; —CH 2 CH 2 C(═O)—; —CH 2 OC(═S)—; —CH 2 CH 2 C(—NR 12 )— where R 12 loweralkyl; —C(═O)CH 2 C(O)—; and —CH 2 OS(═O)(═O)OCH 2 —.
2. A compound according to claim 1 wherein X is —CH═N—.
3. A compound according to claim 1 wherein X is —CH 2 NH—.
4. A compound according to claim 1 wherein D is —CH 2 OC(═CH 2 )—.
5. A compound according to claim 1 wherein D is —CH 2 CH 2 C(═O)—.
6. A compound according to claim 1 wherein D is —CH 2 CH 2 C(—NR 12 )— where R 12 is loweralkyl.
7. A compound according to claim 1 wherein D is —C(═O)CH 2 C(O)—.
8. A compound according to claim 1 wherein D is —CH 2 OS(═O)(═O)OCH 2 —.