Oligo-benzamide compounds and their use

Patent metadata

Field	Value
Publication number	US-10618869-B2
Application number	US-201815860095-A
Country	US
Kind code	B2
Filing date	Jan 2, 2018
Priority date	May 28, 2010
Publication date	Apr 14, 2020
Grant date	Apr 14, 2020

Abstract

The present invention includes bis- and tris-benzamide compounds that block AR signaling and have anticancer activity. Uses for these compounds, and pharmaceutical compositions containing the same, also are provided.

First claim

What is claimed:

1. A compound of formula (A):

wherein:
R 1 and R 2 are each independently C 1 -C 10 alkyl, C 2 -C 10 alkenyl, C 2 -C 10 alkynyl, C 1 -C 15 optionally substituted arylalkyl, —(CH 2 ) n —COOR, —(CH 2 ) n —CONRR′, —(CH 2 ) n —NRR′, —(CH 2 ) n —NH(C═NH)NRR′, —(CH 2 ) n —NRCOR′, —(CH 2 ) n —NRCOOR′, —(CH 2 ) n —OR, —(CH 2 ) n —SR, —(CH 2 ) n —SO m R, —(CH 2 ) n —PO m R, wherein n and m may be any number between 0 and 6 and R and R′ may be a H, C 1 -C 10 alkyl, C 1 -C 10 alkenyl, C 1 -C 10 alkynyl, or C 1 -C 15 optionally substituted arylalkyl group;
X is —NO 2 or —NHC(O)CH 2 R 3 , wherein R 3 is —NO 2 , —NH 2 , —Z, C 1 -C 10 alkyl, C 1 -C 10 alkenyl, C 1 -C 10 alkynyl, or C 1 -C 15 arylalkyl, each of which is optionally substituted with —COOR, —CONRR′, —NRR′, —NH(C═NH)NRR′, —NRCOR′, —NRCOOR′, —OR, —SR, —SO nR , or —PO n R, wherein n may be any number between 0 and 6 and R and R′ may be a H, C 1 -C 10 alkyl, C 2 -C 10 alkenyl, C 2 -C 10 alkynyl, or C 1 -C 15 optionally substituted arylalkyl group, and wherein Z is:

and
Y is —(CH 2 ) n CONR 4 R 5 , —(CH 2 ) n NR 4 R 5 , —(CH 2 ) n —NR 4 R 5 , —(CH 2 ) n —NH(C═NH)NR 4 R 5 , —(CH 2 ) n —NR 4 COR 5 , —(CH 2 ) n —NR 4 COOR 5 , —(CH 2 ) n —OR 4 , —(CH 2 ) n —SR 4 , —(CH 2 ) n —SO m R 4 , —(CH 2 ) n —PO m R 4 , wherein n and m may be any number between 0 and 6, R 4 and R 5 are independently selected from —H, C 1 -C 10 alkyl, C 2 -C 10 alkenyl, C 2 -C 10 alkynyl, or C 1 -C 15 optionally substituted arylalkyl group; or
Y is —(CH 2 ) n COOR 4 , wherein R 4 is —H or C 1 -C 10 alkenyl.

2. The compound of claim 1 , wherein X is —NO 2 .

3. The compound of claim 2 , wherein
R 1 and R 2 are C 1 -C 10 alkyl, C 2 -C 10 alkenyl, or C 2 -C 10 alkynyl,
R 1 and R 2 are optionally substituted C 1 -C 15 arylalkyl,
R 1 and R 2 are —(CH 2 ) n —NRR′ or —(CH 2 ) n —NH(C═NH)NRR′ groups, wherein n may be any number between 0 and 6 and R and R′ may be a H, C 1 -C 10 alkyl, C 2 -C 10 alkenyl, C 2 -C 10 alkynyl, or C 1 -C 15 optionally substituted arylalkyl,
R 1 and R 2 are —(CH 2 ) n —COOR, —(CH 2 ) n —CONRR′, —(CH 2 ) n —NRCOR′, —(CH 2 ) n —NRCOOR′, —(CH 2 ) n —SO m R, —(CH 2 ) n —PO m R, wherein n and m may be any number between 0 and 6 and R and R′ may be a H, C 1 -C 10 alkyl, C 2 -C 10 alkenyl, C 2 -C 10 alkynyl, or C 1 -C 15 optionally substituted arylalkyl,
R 1 and R 2 are —(CH 2 ) n —OR, —(CH 2 ) n —SR, wherein R may be a H, C 1 -C 10 alkyl, C 2 -C 10 alkenyl, C 2 -C 10 alkynyl, or C 1 -C 15 optionally substituted arylalkyl,
R 1 is C 1 -C 15 optionally substituted arylalkyl, and R 2 is C 1 -C 10 alkyl, C 2 -C 10 alkenyl, or C 2 -C 10 alkynyl,
R 1 is C 1 -C 10 alkyl, C 2 -C 10 alkenyl, or C 2 -C 10 alkynyl, and R 2 is C 1 -C 15 optionally substituted arylalkyl,
R 1 is —(CH 2 ) n —NRR′ or —(CH 2 ) n —NH(C═NH)NRR′, and R 2 is —(CH 2 ) n —COOR, —(CH 2 ) n —SO m R, —(CH 2 ) n —PO m R, wherein n and m may be any number between 0 and 6 and R and R′ may be a H, C 1 -C 10 alkyl, C 2 -C 10 alkenyl, C 2 -C 10 alkynyl, or C 1 -C 15 optionally substituted arylalkyl group, or
R 1 is —(CH 2 ) n —COOR, —(CH 2 ) n —SO m R, —(CH 2 ) n —PO m R, and R 2 is —(CH 2 ) n —NRR′ or —(CH 2 ) n —NH(C═NH)NRR′, wherein n and m may be any number between 0 and 6 and R and R′ may be a H, C 1 -C 10 alkyl, C 2 -C 10 alkenyl, C 2 -C 10 alkynyl, or C 1 -C 15 optionally substituted arylalkyl group.

4. The compound of claim 1 , wherein X is —NHC(O)CH 2 R 3 and R 3 is —NH 2 or C 1 -C 10 alkyl, optionally substituted with —COOH.

5. The compound of claim 1 , wherein Y is —NH 2 .

6. The compound of claim 1 , wherein the compound is:

7. A pharmaceutical composition comprising a compound as shown in claim 1 , dispersed in a pharmaceutically acceptable carrier, buffer or diluent.

8. A method of inhibiting an androgen receptor (AR)-positive tumor cell comprising administering to a subject in need thereof a therapeutically sufficient amount of a compound as shown in claim 1 .

9. The method of claim 8 , wherein the AR-positive tumor cell is a carcinoma cell, a leukemia cell or a myeloma cell.

10. The method of claim 9 , wherein the carcinoma cell is a prostate or breast carcinoma cell.

Assignees

• Univ Texas

Inventors

• Ahn Jung-Mo
• Raj Ganesh

Classifications

• C07C235/56 Primary

  having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a six-membered aromatic ring · CPC title

• C07C279/08

  being further substituted by singly-bound oxygen atoms · CPC title

• A61P13/08

  of the prostate · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61K31/167

  having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol · CPC title