NOVEL 1,4-BENZODIAZEPINE-2,5-DIONES WITH THERAPEUTIC PROPERTIES
The present invention relates to novel chemical compounds, methods for their discovery, and their therapeutic use. In particular, the present invention provides novel 1,4-benzodiazepine-2,5-dione compounds, and methods of using novel 1,4-benzodiazepine-2,5-dione compounds as therapeutic agents to treat a number of conditions associated with the faulty regulation of the processes of programmed cell death, autoimmunity, inflammation, hyperproliferation, and the like.
1 . A composition configured to induce apoptosis in a cell, said composition comprising a compound described by a formula selected from the group consisting of:
substituted and unsubstituted, including both R and S enantiomeric forms and racemic mixtures;
wherein R1 is an electron rich heterocycle;
wherein R2 is selected from the group consisting of H, alkyl, substituted alkyl, and R 1 ;
wherein R 3 is selected from the group consisting of H, alkyl, and substituted alkyl;
wherein R 4 and R 4 ′ is independently selected from the group consisting of CH 3 , halogen, SO 2 R 4 ″, SO 2 N(R 4 ″) 2 , OR 4 ″, N(R 4 ″) 2 , CON(R 4 ″) 2 , NHCOR 4 ″, NHSO 2 R 4 ′, alkyl, mono-substituted alkyl, di-substituted alkyl, tri-substituted alkyl; wherein R 4 ″ is selected from the group consisting of halogen, H, alkyl, mono-substituted alkyl, di-substituted alkyl, tri-substituted alkyl, aryl, mono-substituted aryl, di-substituted aryl, tri-substituted aryl, cycloalipathic, mono-substituted cycloalipathic, di-substituted cycloalipathic, tri-substituted cycloalipathic;
wherein R 5 is selected from the group consisting of H, alkyl, mono-substituted aryl, di-substituted aryl, and tri-substituted aryl; and
wherein R6 is selected from the group consisting of C, N or S.
2 . The composition of claim 1 , wherein said electron rich heterocycle contains 5 or more heterocyclic atoms.
3 . The composition of claim 1 , wherein R 1 is selected from the group consisting of
wherein R 1 ′ is selected from the group consisting of cycloalipathic, aryl, substituted aryl, heterocyclic, and substituted heterocyclic.
4 . The composition of claim 1 , wherein R1 is selected from the group consisting of:
In some embodiments, R1 is selected from the group consisting of:
and derivatives thereof.
5 . The composition of claim 1 , wherein said compound is described by the following formula:
6 . The composition of claim 1 , wherein said compound is selected from the group consisting of:
7 . The composition of claim 1 , wherein said cells are selected from the group consisting of B cells, T cells, granulocytes, and proliferating cells.
8 . A method for regulating cell death, comprising
a. providing:
i. target cells;
the position described in claim 1 ; and
b. exposing said target cells to said composition under conditions such that said composition binds to said target cells so as to induce cellular apoptosis.
9 . The method of claim 8 , wherein said target cells are in vitro cells.
10 . The method of claim 8 , wherein said target cells are in vivo cells.
11 . The method of claim 8 , wherein said target cells are ex vivo cells.
12 . The method of claim 8 , wherein said target cells are cancer cells.
13 . The method of claim 8 , wherein said target cells are selected from the group consisting of B cells, T cells, and granulocytes.
14 . The method of claim 8 , wherein said target cells are proliferating cells.
15 . A method of treating autoimmune disorders, comprising:
a) providing a subject and the composition described in claim 1 , wherein said composition is capable of inducing cellular apoptosis, and wherein said composition demonstrates selective cytotoxicity against T cells as compared to B cells; and
b) administering said composition to said subject.