Diazabenzo[de] anthracen-3-one compounds and methods for inhibiting PARP
The present invention relates to diazabenzo[de]anthracen-3-one compounds which inhibit poly(ADP-ribose) polymerase (“PARP”), compositions containing these compounds and methods for using these PARP inhibitors to treat, prevent and/or ameliorate the effects of the conditions described herein.
1. A combination comprising
(i) the compound
or a pharmaceutically acceptable salt, ester or mixture thereof; and
(ii) temozolomide.
2. The combination of claim 1 , wherein the compound is a maleate salt of
3. A pharmaceutical composition comprising
(i) the compound
or a pharmaceutically acceptable salt, ester or mixture thereof;
(ii) temozolomide; and
(iii) a pharmaceutically acceptable carrier, diluent, or excipient.
4. The pharmaceutical composition of claim 3 , wherein the compound is a maleate salt of
5. A method for treating cancer comprising administering an effective amount of a combination comprising
(i) the compound
or a pharmaceutically acceptable salt, ester or mixture thereof; and
(ii) temozolomide;
wherein the cancer is melanoma.
6. The method of claim 5 , wherein the compound is a maleate salt of
7. The method of claim 5 , wherein the compound
is administered in an amount sufficient to potentiate the antitumor activity of temozolomide.
8. The method of claim 5 , wherein the cancer is a tumor.
9. The method of claim 5 , further comprising
(a) first: allowing a time period following administration of said compound to provide an effective amount of chemo sensitization, and,
(b) second: administering to said mammal a pharmaceutically-effective dose of temozolomide.
10. The method of claim 6 , further comprising
(a) first: allowing a time period following administration of said compound to provide an effective amount of chemo sensitization, and,
(b) second: administering to said mammal a pharmaceutically-effective dose of temozolomide.
11. The method of claim 5 , wherein said compound and temozolomide are administered essentially simultaneously.
12. The method of claim 6 , wherein said compound and temozolomide are administered essentially simultaneously.
13. The method of claim 5 , wherein the melanoma is located at a site in the central nervous system.