Oligo-benzamide compounds and their use

Patent metadata

Field	Value
Publication number	US-9856206-B2
Application number	US-201514932480-A
Country	US
Kind code	B2
Filing date	Nov 4, 2015
Priority date	May 28, 2010
Publication date	Jan 2, 2018
Grant date	Jan 2, 2018

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 formulas (A) or (B):

wherein:
R 1 and R 2 are each independently C 1 -C 10 alkyl, C 1 -C 10 alkenyl, C 1 -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 n R, 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 1 -C 10 alkenyl, C 1 -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 1 -C 10 alkenyl, C 1 -C 10 alkynyl, or C 1 -C 15 optionally substituted arylalkyl group; or

wherein:
R 1 , R 2 and R 3 are each independently C 1 -C 10 alkyl, C 1 -C 10 alkenyl, C 1 -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 or

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 n R, 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 1 -C 10 alkenyl, C 1 -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 1 -C 10 alkenyl, C 1 -C 10 alkynyl, or C 1 -C 15 optionally substituted arylalkyl group.

2. The compound of claim 1 , further defined as a compound of formula (A).

3. The compound of claim 1 , further defined as a compound of formula (B).

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

5. The compound of claim 3 , wherein X′ is —NO 2 .

6. The compound of claim 4 , wherein:
R 1 and R 2 are C 1 -C 10 alkyl, C 1 -C 10 alkenyl, or C 1 -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 —(CH2) 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 1 -C 10 alkenyl, C 1 -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 1 -C 10 alkenyl, C 1 -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 1 -C 10 alkenyl, C 1 -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 1 -C 10 alkenyl, or C 1 -C 10 alkynyl,
R 1 is C 1 -C 10 alkyl, C 1 -C 10 alkenyl, or C 1 -C 10 alkynyl, and R 2 is C-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 1 -C 10 alkenyl, C 1 -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 1 -C 10 alkenyl, C 1 -C 10 alkynyl, or C 1 -C 15 optionally substituted arylalkyl group.

7. The compound of claim 5 , wherein:
R 1 , R 2 , and R 3 are C 1 -C 10 alkyl, C 1 -C 10 alkenyl, or C 1 -C 10 alkynyl,
R 1 , R 2 , and R 3 are optionally substituted C 1 -C 15 arylalkyl,
R 1 , R 2 , and R 3 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 1 -C 10 alkenyl, C 1 -C 10 alkynyl, or C 1 -C 15 optionally substituted arylalkyl,
R 1 , R 2 , and R 3 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 1 -C 10 alkenyl, C 1 -C 10 alkynyl, or C 1 -C 15 optionally substituted arylalkyl,
R 1 , R 2 , and R 3 are —(CH 2 ) n —OR, —(CH 2 ) n —SR, wherein 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,
R 1 is C 1 -C 15 optionally substituted arylalkyl, and R 2 and R 3 are C 1 -C 10 alkyl, C 1 -C 10 alkenyl, or C 1 -C 10 alkynyl,
R 1 and R 2 are C 1 -C 10 alkyl, C 1 -C 10 alkenyl, or C 1 -C 10 alkynyl, and R 3 is C 1 -C 15 optionally substituted arylalkyl,
R 1 is C 1 -C 10 alkyl, C 1 -C 10 alkenyl, or C 1 -C 10 alkynyl, and R 2 and R 3 are C 1 -C 15 optionally substituted arylalkyl,
R 1 and R 2 are C 1 -C 15 optionally substituted arylalkyl, and R 3 is C 1 -C 10 alkyl, C 1 -C 10 alkenyl, or C 1 -C 10 alkynyl,
R 1 and R 3 are C 1 -C 10 alkyl, C 1 -C 10 alkenyl, or C 1 -C 10 alkynyl, and R 2 is C 1 -C 15 optionally substituted arylalkyl,
R 1 and R 3 are C 1 -C 15 optionally substituted arylalkyl, and R 2 is C 1 -C 10 alkyl, C 1 -C 10 alkenyl, or C 1 -C 10 alkynyl,
R 1 and R 2 are —(CH 2 ) n —NRR′ or —(CH 2 ) n —NH(C═NH)NRR′, and R 3 is C 1 -C 10 alkyl, C 1 -C 10 alkenyl, or C 1 -C 10 alkynyl, wherein n 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 sub

Assignees

• Univ Texas

Inventors

• Ahn Jung-Mo
• Raj Ganesh

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61P43/00

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

• A61P35/02

  specific for leukemia · CPC title

• A61P13/08

  of the prostate · CPC title

• C07C279/08

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