Fused diimidazodiazepine compounds and methods of use and manufacture thereof
The invention encompasses novel compounds and pharmaceutically acceptable salts thereof and compositions including therapeutically or prophylactically effective amounts of such compounds or pharmaceutically acceptable salts thereof. The invention also encompasses methods for treating or preventing diseases and disorders associated abnormal cell growth, for example, treating or preventing cancer or tumor growth, which methods include administering to a mammal in need thereof a composition comprising a therapeutically or prophylactically effective amount of a compound of the invention or a pharmaceutically acceptable salt thereof.
1. A compound of Formula (I):
(I) or pharmaceutically acceptable salts and prodrugs thereof, wherein:
R, R′, and R″ are each independently a hydrogen; hydroxyl; substituted or unsubstituted: cyclic or acyclic alkyl group, cyclic or acyclic alkenyl group, cyclic or acyclic alkynyl group, aryl group, alkylaryl group, arylalkyl group, benzyl group, cyclic or acyclic heteroalkyl group, heteroaryl group; —C(O)R 3 ; —C(S)R 3 ; —S(O) 2 R 3 ; —C(O)NR 3 R 4 ; —C(S)NR 3 R 4 ; —C(S)YR 3 ; —C(O)YR 3 ; -β-D-ribosyl; -α-D-ribosyl; -β-L-ribosyl; -α-L-ribosyl; 2′-deoxy-β-D-ribosyl; 2′-deoxy-β-L-ribosyl; 2′-deoxy-α-D-ribosyl; 2′-deoxy-α-L-ribosyl; or ribose or deoxyribose sugars substituted with one or more halogens;
When Q is present, represents a double bond and Q is O, NH, or S;
Y is O or S;
R 3 and R 4 are independently a hydrogen; hydroxyl; substituted or unsubstituted: cyclic or acyclic alkyl group, cyclic or acyclic alkenyl group, cyclic or acyclic alkynyl group, aryl group, alkylary group, aryalkyl group, heteroaryl group, heterocycloalkyl group; and
r, r′, and r″ are each independently an integer from 1 to 3.
2. The compound of claim 1 , wherein R is a substituted benzyl.
3. The compound of claim 1 , wherein R′ is a substituted benzyl.
4. The compound of claim 1 , wherein R″ is a substituted phenyl.
5. The compound of claim 1 , wherein R and R′ are each a substituted benzyl.
6. The compound of claim 1 , wherein R is cyclic or acyclic alkyl; aryl; heterolkyl; or heteroaryl.
7. The compound of claim 1 , wherein R′ is cyclic or acyclic alkyl; aryl; heterolkyl; or heteroaryl.
8. The compound of claim 6 , wherein the cyclic or acyclic alkyl; aryl; heteroalkyl; heteroaryl are substituted.
9. The compound of claim 7 , wherein the cyclic or acyclic alkyl aryl; heteroalkyl; and heteroaryl are substituted.
10. The compound of claim 1 , wherein R″ is hydrogen, R is a substituted benzyl, and R′ is a substituted benzyl.
11. The compound of claim 1 , wherein R″ is hydrogen, R is p-methoxybenzyl, and R′ is p-methoxy-benzyl.
12. The compound of claim 1 , selected from the group consisting of:
wherein x and y are integers from 1-17;
wherein x and y are integers from 1-10;
13. The compound of claim 1 , wherein R is covalently bonded to the 7-position.
14. The compound of claim 1 , wherein R′ is covalently bonded to the 3-position.
15. The compound of claim 1 , wherein R″ is a substituted phenyl.
16. The compound of claim 15 , wherein the substituted phenyl is p-methoxyphenyl.
17. The compound of claim 1 , wherein R is hydrogen, R′ is p-methoxybenzyl and R″ is p-methoxy-phenyl.
18. The compound of claim 1 , wherein R is hydrogen, R′ is p-methoxybenzyl and R″ is p-methoxy-phenyl and R′ is substituted on the 3 position, R″ is substituted on the 9(b) position and Q is oxygen.
19. A composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier.
20. A method for treating breast cancer comprising administering to a mammal in need thereof a composition comprising a therapeutically acceptable compound of claim 1 .
21. The compound of claim 1 that is
22. The composition of claim 19 , wherein at least one of R, R′, and R″ is a substituted benzyl.
23. The composition of claim 19 , wherein R and R′ are each a substituted benzyl.
24. The composition of claim 19 , wherein at least one of R and R′ is cyclic or acyclic alkyl; aryl; heteroalkyl; or heteroaryl, wherein the cyclic or acyclic alkyl, aryl, heteroalkyl or heteroaryl is optionally substituted.
25. The composition of claim 19 , wherein R″ is hydrogen, R is a substituted benzyl, and R′ is a substituted benzyl.
26. The composition of claim 19 , wherein R″ is hydrogen, R is p-methoxybenzyl, and R′ is p-methoxy-benzyl.
27. The composition of claim 19 , wherein R is hydrogen, R′ is 3-(p-methoxybenzyl) and R″ is 9(b)-(p-methoxy-phenyl) and Q is oxygen.
28. The composition of claim 19 , wherein the compound is selected from the group consisting of
wherein x and y are integers from 1-17;
wherein x and y are integers from 1-10;
29. The composition of claim 19 , wherein the compound is
30. The method of claim 20 , wherein at least one of R, R′, and R″ is a substituted benzyl.
31. The method of claim 20 , wherein R and R′ are each a substituted benzyl.
32. The method of claim 20 , wherein at least one of R and R′ is cyclic or acyclic alkyl; aryl; heteroalkyl; or heteroaryl, wherein the cyclic or acyclic alkyl, aryl, heteroalkyl or heteroaryl is optionally substituted.
33. The method of claim 20 , wherein R″ is hydrogen, R is a substituted benzyl, and R′ is a substituted benzyl.
34. The method of claim 20 , wherein R″ is hydrogen, R is p-methoxybenzyl, and R′ is p-methoxy-benzyl.
35. The method of claim 20 , wherein R is hydrogen, R′ is 3-(p-methoxybenzyl) and R″ is 9(b)-(p-methoxy-phenyl) and Q is oxygen.
36. The composition of claim 19 , wherein the compound is selected from the group consisting of
wherein x and y are integers from 1-17;
wherein x and y are integers from 1-10;
37. The method of claim 20 , wherein the compound is