Small molecules for disrupting the super elongation complex and inhibiting transcription elongation for cancer therapy

Patent metadata

Field	Value
Publication number	US-11453640-B2
Application number	US-201916981654-A
Country	US
Kind code	B2
Filing date	Mar 21, 2019
Priority date	Mar 21, 2018
Publication date	Sep 27, 2022
Grant date	Sep 27, 2022

Abstract

Disclosed are compounds which may be utilized to inhibit transcription by RNA Polymerase II (Pol II), and in particular to disrupt the Super Elongation Complex (SEC). The compounds may be utilized in pharmaceutical compositions and methods for treating diseases and disorders associated with the biological activity of SEC, and in particular, diseases and disorders that are associated with high levels of expression of genes whose expression is SEC-dependent and that promote, support, or otherwise are required for the disease or disorder such as cancers.

First claim

We claim:

1. The pharmaceutical composition comprising a compound of formula

or a tautomer or pharmaceutical salt thereof and a pharmaceutically acceptable carrier.

2. A method for treating a disease or disorder associated with Super Elongation Complex (SEC) activity in a subject in need thereof, the method comprising administering to the subject the pharmaceutical composition according to claim 1 , wherein the pharmaceutical composition comprises an effective amount of the compound for treating the disease or disorder and wherein the disease or disorder is a cell proliferative disease or disorder associated with relatively high levels of Myc expression.

3. A method for treating a disease or disorder associated with Super Elongation Complex (SEC) activity in a subject in need thereof, the method comprising administering to the subject the pharmaceutical composition according to claim 1 , wherein the pharmaceutical composition comprises an effective amount of the compound for treating the disease or disorder and wherein the disease or disorder is associated with expression of a mixed lineage leukemia (MLL) chimera.

4. A method for treating a disease or disorder associated with Super Elongation Complex (SEC) activity in a subject in need thereof, the method comprising administering to the subject the pharmaceutical composition according to claim 1 , wherein the pharmaceutical composition comprises an effective amount of the compound for treating the disease or disorder and wherein the disease or disorder is acute myeloid leukemia (AML) or acute lymphoid leukemia (ALL).

5. A method for treating a disease or disorder associated with Super Elongation Complex (SEC) activity in a subject in need thereof, the method comprising administering to the subject the pharmaceutical composition according to claim 1 , wherein the pharmaceutical composition comprises an effective amount of the compound for treating the disease or disorder and wherein the disease or disorder is infection by human immunodeficiency virus (HIV).

Assignees

• Univ Northwestern

Inventors

• Shilatifard Ali
• Liang Kaiwei
• Smith Edwin R
• Schiltz Gary E
• Mishra Rama K
• Stoltz Kristen

Classifications

• C07D231/14

  with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms · CPC title

• C07D213/75

  Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates · CPC title

• C07D271/07

  with oxygen, sulfur or nitrogen atoms, directly attached to ring carbon atoms, the nitrogen atoms not forming part of a nitro radical · CPC title

• C07D257/06

  with nitrogen atoms directly attached to the ring carbon atom · CPC title

• C07C235/78

  the carbon skeleton containing rings · CPC title