Inhibitors of late SV40 factor (LSF) as cancer chemotherapeutics

Patent metadata

Field	Value
Publication number	US-9802948-B2
Application number	US-201615389564-A
Country	US
Kind code	B2
Filing date	Dec 23, 2016
Priority date	Oct 13, 2010
Publication date	Oct 31, 2017
Grant date	Oct 31, 2017

Abstract

The present invention is directed to methods, compositions and kits for treatment of cancer, e.g. heptacellular carcinoma. In some embodiments, the present invention discloses the use of a small-molecule compound of formula (I)-(XXVI) and (III′) as disclosed herein to inhibit transcription factor Late SV40 Factor (LSF) for treatment of cancer, e.g., HCC.

First claim

What is claimed is:

1. A compound of formula (III′), wherein the Formula (III′) has the structure:

wherein:
R 1′ is an aryl substituted with at least one C 1 -C 6 alkoxyl and at least one di(C 1 -C 24 alkyl)amino, halogen or C 2 -C 8 alkenyl, wherein the substituted aryl can be optionally further substituted with halogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 heteroalkyl, di(C 1 -C 24 alkyl)amino or combinations thereof;
R 2 and R 3 are hydrogen or R 2 and R 3 together form a second bond between the carbons to which they are attached;
R 4 is hydrogen;
R 5 is selected from the group consisting of hydrogen and C 1 -C 6 alkyl;
R 6 and R 7 are each independently selected from the group consisting of hydrogen, F, Br, Cl and I;
R 10 and R 11 are each independently selected from the group consisting of hydrogen, F, Br, Cl, and I;
or enantiomers, prodrugs, derivatives, and pharmaceutically acceptable salts thereof, and
wherein the compound is capable of inhibiting late SV40 factor (LSF).

2. The compound of claim 1 , wherein R 1′ is a phenyl substituted with at least one C 1 -C 6 alkoxyl and at least one di(C 1 -C 24 alkyl)amino, halogen or C 2 -C 8 alkenyl.

3. The compound of claim 2 , wherein R 1′ is

wherein R 21 is C 1 -C 6 alkyl; R 22 and R 23 are independently selected C 1 -C 24 alkyl; R 24 is halogen; and R 25 is C 2 -C 8 alkenyl.

4. The compound of claim 3 , wherein R 1′ is

5. The compound of claim 1 , wherein the compound is selected from the groups consisting of

6. The compound of claim 1 , wherein the compound is FQI-34.

7. A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable excipient or carrier.

Assignees

• Univ Boston
• Trustees Of Boston Univeristy

Inventors

• Hansen Ulla
• Schaus Scott
• Grant Trevor
• Bishop Joshua
• Kavouris John
• Christadore Lisa M

Classifications

• C07D491/056 Primary

  with two or more oxygen atoms as ring hetero atoms in the oxygen-containing ring · CPC title

• C07D215/16

  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

• C07D215/22

  attached in position 2 or 4 · CPC title

• C07D215/227

  only one oxygen atom which is attached in position 2 · CPC title