Tubulin inhibitors
The present invention relates to novel tubulin binding molecules of formula (I) and their use for the treatment of cancer and other diseases.
1. Compound of formula (I):
wherein
R is C 1 -C 6 alkyl;
R′ is —O—CO-alkyl, alkyl, —O-alkyl, or —O-alkyl-O-alkyl;
R″ is a group of formula CO 2 H, CO 2 R′″, CONHR′″, CONR 2 ′″, with R′″ independently being an alkyl, aryl, aralkyl or heteroalkyl group;
X is S or O;
Y is independently optionally substituted alkyl, optionally substituted heteroalkyl, halogen, CN, NO 2 or OH;
n is 0, 1, 2, 3, 4 or 5;
or a pharmacologically acceptable salt, solvate, hydrate or a pharmacologically acceptable formulation thereof.
2. Compound according to claim 1 , wherein R″ is CO 2 H.
3. Compound according to claim 1 , wherein R″ is a group of formula CO 2 R′″, CONHR′″ or CONR 2 ′″, with R′″ being an alkyl, aryl, aralkyl or heteroalkyl group.
4. Compound according to claim 1 , wherein X is S.
5. Compound according to claim 1 , wherein Y is independently optionally substituted alkyl, halogen or OH and n is 1.
6. Compound according to claim 1 , wherein n is 0.
7. Compound of formula (I)
wherein R is propyl, R′ is O-Acetyl, X is S, n is 0 and R″ is CO 2 H.
8. Pharmaceutical composition containing a compound according to claim 1 and optionally one or more carriers or adjuvants.
9. A method for preventing or treating cancer comprising administering a compound of claim 1 to a subject in need thereof, thereby preventing or treating the subject's cancer.
10. A method for preventing or treating cancer comprising administering a pharmaceutical composition of claim 8 to a subject in need thereof, thereby preventing or treating the subject's cancer.