Naphthalene-based inhibitors of anti-apoptotic proteins
Methods of using apogossypol and its derivatives for treating inflammation is disclosed. Also, there is described a group of compounds having structure A, or a pharmaceutically acceptable salt, hydrate, N-oxide, or solvate thereof are provided: wherein each R is independently selected from the group consisting of H, C(O)X, C(O)NHX, NH(CO)X, SO 2 NHX, and NHSO 2 X, wherein X is selected from the group consisting of an alkyl, a substituted alkyl, an aryl, a substituted aryl, an alkylaryl, and a heterocycle. Compounds of group A may be used for treating various diseases or disorders, such as cancer.
1. A compound having the structure B:
wherein
each of R 6 , R 8 , R 9 and R 10 is independently selected from the group consisting of hydrogen, hydroxyl, —(C 1 -C 6 )alkyl, —O(C 1 -C 6 )alkyl, —(C 1 -C 6 )alkylhalo, —OC(O)(C 1 -C 6 )alkyl, and halo; and
each R 7 is independently selected from the group consisting of (C 3 -C 8 )cycloalkyl, —(C 6 -C 10 )aryl, and —(C 1 -C 6 )alkyl(C 6 -C 10 )aryl, C(O)X, NH(CO)X, SO 2 NHX, and NHSO 2 X, wherein X is selected from the group consisting of an alkyl, a substituted alkyl, an aryl, a substituted aryl, an alkylaryl, a substituted alkylaryl and a heterocycle, or a pharmaceutically acceptable salt, hydrate, N-oxide, or solvate thereof.
2. The compound of claim 1 , wherein each of R 6 and R 10 is independently selected from the group consisting of —(C 1 -C 6 )alkyl, and —O(C 1 -C 6 )alkyl.
3. The compound of claim 1 , wherein each of R 8 and R 9 is independently selected from the group consisting of hydrogen, and hydroxyl.
4. The compound of claim 1 , wherein R 8 and R 9 are hydroxyl.
5. The compound of claim 1 , wherein the compound is selected from the group consisting of compounds I, III-XX, and XXII: