Aminobenzimidazole derivatives, treatments, and methods of inhibiting histone deacetylase
AssigneeTranslational Drug Development, LLC
InventorsTong Wang, Stephen Gately
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Abstract
The present invention is directed to novel aminobenzimidazole derivatives. The present invention is also directed to methods of treating a histone deacetylase (HDAC)-associated disease or inhibiting the histone deacetylating activity of a HDAC isoform in a cell or with one or more of the aminobenzimidazole derivatives.
Claims20
A method of inhibiting the histone deacetylating activity of a histone deacetylase (HDAC) isoform in a cell, comprising contacting the cell with a compound of formula (I):
- wherein:
- X is selected from the group consisting of:
- H, halo, —C1-C6 alkyl, aryl, —C3-C7 cycloalkyl, and -3- to 10-membered heterocycle, any of which is unsubstituted, or substituted with one or more of:
- -halo, —C1-C6 alkyl, —O—(C1-C6 alkyl), —OH, —CN, —COOR′, —OC(O)R′, NHR′, N(R′)2, —NHC(O)R′, and —C(O)NHR′, wherein R′ is —H or —C1-C6 alkyl;
- A is selected from the group consisting of:
- a bond, —C1-C6 alkyl, and —C3-C7 cycloalkyl, any of which is unsubstituted, or substituted with one or more of:
- -halo, —C1-C6 alkyl, —O—(C1-C6 alkyl), —OH, —CN, —COOR′, —OC(O)R′, NHR′, N(R′)2, —NHC(O)R′, and —C(O)NHR′, wherein R′ is —H or —C1-C6 alkyl;
- Y is selected from the group consisting of:
- H, —C1-C6 alkyl, —C3-C7 cycloalkyl, aryl, and -3- to 10-membered heterocycle, any of which is unsubstituted, or substituted with one or more of:
- -halo, —C1-C6 alkyl, —O—(C1-C6 alkyl), —OH, —CN, —COOR′, —OC(O)R′, NHR′, N(R′)2, —NHC(O)R′, and —C(O)NHR′, wherein R′ is —H or —C1-C6 alkyl;
- and
- Q is selected from the group consisting of:
- —H, -halo, —C1-C6 alkyl, —O—(C1-C6 alkyl), —OH, —CN, —COOR′, —OC(O)R′, NHR′, N(R′)2, —NHC(O)R′, and —C(O)NHR′, wherein R′ is —H or —C1-C6 alkyl;
- wherein the compound inhibits the histone deacetylating activity of the HDAC isoform in the cell.
A method of treating a subject having a disease by inhibiting an HDAC isoform, comprising administering to the subject a compound of formula (I):
- wherein:
- X is selected from the group consisting of:
- H, halo, —C1-C6 alkyl, aryl, —C3-C7 cycloalkyl, and -3- to 10-membered heterocycle, any of which is unsubstituted, or substituted with one or more of:
- -halo, —C1-C6 alkyl, —O—(C1-C6 alkyl), —OH, —CN, —COOR′, —OC(O)R′, NHR′, N(R′)2, —NHC(O)R′, and —C(O)NHR′, wherein R′ is —H or —C1-C6 alkyl;
- A is selected from the group consisting of:
- a bond, —C1-C6 alkyl, and —C3-C7 cycloalkyl, any of which is unsubstituted, or substituted with one or more of:
- -halo, —C1-C6 alkyl, —O—(C1-C6 alkyl), —OH, —CN, —COOR′, —OC(O)R′, NHR′, N(R′)2, —NHC(O)R′, and —C(O)NHR′, wherein R′ is —H or —C1-C6 alkyl;
- Y is selected from the group consisting of:
- H, —C1-C6 alkyl, —C3-C7 cycloalkyl, aryl, and -3- to 10-membered heterocycle, any of which is unsubstituted, or substituted with one or more of:
- -halo, —C1-C6 alkyl, —O—(C1-C6 alkyl), —OH, —CN, —COOR′, —OC(O)R′, NHR′, N(R′)2, —NHC(O)R′, and —C(O)NHR′, wherein R′ is —H or —C1-C6 alkyl;
- and
- Q is selected from the group consisting of:
- —H, -halo, —C1-C6 alkyl, —O—(C1-C6 alkyl), —OH, —CN, —COOR′, —OC(O)R′, NHR′, N(R′)2, —NHC(O)R′, and —C(O)NHR′, wherein R′ is —H or —C1-C6 alkyl;
- wherein the compound inhibits the histone deacetylating activity of the HDAC isoform and the disease is a cancer selected from the group consisting of acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML), acute promyelocytic leukemia (APL), breast cancer, chronic myeloid leukemia (CML), gastrointestinal stromal tumor (GIST), glioblastoma (GBM), lymphoma, myeloma, ovarian cancer, uterine cancer, and non-small cell lung cancer (NSCLC).
Dependencies are inferred from the claim text.