Linked diaryl compounds with anticancer properties and methods of using the same

Patent metadata

Field	Value
Publication number	US-10130625-B2
Application number	US-201515327485-A
Country	US
Kind code	B2
Filing date	Jul 22, 2015
Priority date	Jul 22, 2014
Publication date	Nov 20, 2018
Grant date	Nov 20, 2018

Abstract

Provided are compositions comprising linked diaryl compounds that possess anticancer properties. Methods of use are also disclosed herein. The method comprises administering an effective amount of a compound described herein to an individual in need thereof.

First claim

The invention claimed is:

1. A compound having the following formula:

wherein
W is selected from the group consisting of —R 1 , —OR 1 , —N(R 1 ) 2 , —NO 2 , -halogen,

wherein
E is selected from the group consisting of oxygen atom, sulfur atom, —N(R 1 )—, and —N(OR 1 )—;
X is —N—, or —C(R 1 )—;
Y is selected from the group consisting of —R 1 , -ER 1 , —X(R 1 ) 2 , and -halogen;
n is 0-6; and
R 1 is selected from the group consisting of H, substituted or unsubstituted C 1 -C 14 alkyl, substituted or unsubstituted C 1 -C 14 heteroalkyl, wherein 1-7 of the chain atoms are independently O, N, S, P, or B, substituted or unsubstituted C 1 -C 14 alkenyl, substituted or unsubstituted C 1 -C 14 heteroalkenyl, wherein 1-7 of the chain atoms are independently O, N, S, P, or B, substituted or unsubstituted C 1 -C 14 alkynyl, substituted or unsubstituted C 1 -C 14 heteroalkynyl, wherein 1-7 of the chain atoms are independently O, N, S, P, or B, substituted or unsubstituted C 5 -C 14 aryl, halo, heteroaryl having 5-14 ring atoms, wherein1-8 of the ring atoms are independently O, N, S, P, or B,

 wherein
Y 1 is selected from the group consisting of —OR 1 , —NR 1 , —SR 1 , and —R 1 ;

L is selected from the group consisting of direct bond, —O—, —NH—, —O—(CH 2 ) m —O—, —NH—(CH 2 ) m —NH—,

wherein
m is 2-6;

Q is selected from the group consisting of —OH, —SH, —NR 1 ,

 wherein
A is selected from the group consisting of direct covalent bond, —SO 2 —NH—, —NH—; and
Z is selected from the group consisting of —S—, —O—, -ER 1 —, —CH, —N—, —NH—, —N + (R 1 )—, and —N(R 1 )—.

2. The compound of claim 1 , wherein the compound has the following formula:

wherein
W is selected from the group consisting of —R 1 , —OR 1 , —N(R 1 ) 2 , —NO 2 , -halogen,

wherein
E is selected from the group consisting of oxygen atom, sulfur atom, —N(R 1 )—, and —N(OR 1 )—;
X is —N—, or —C(R 1 )—;
Y is selected from the group consisting of —R 1 , -ER 1 , —X(R 1 ) 2 , and -halogen; and
R 1 is selected from the group consisting of H, substituted or unsubstituted C 1 -C 14 alkyl, substituted or unsubstituted C 1 -C 14 heteroalkyl, wherein 1-7 of the chain atoms are independently O, N, S, P, or B, substituted or unsubstituted C 1 -C 14 alkenyl, substituted or unsubstituted C 1 -C 14 heteroalkenyl, wherein 1-7 of the chain atoms are independently O, N, S, P, or B, substituted or unsubstituted C 1 -C 14 alkynyl, substituted or unsubstituted C 1 -C 14 heteroalkynyl, wherein 1-7 of the chain atoms are independently O, N, S, P, or B, substituted or unsubstituted C 5 -C 14 aryl, halo, heteroaryl having 5-14 ring atoms, wherein 1-8of the ring atoms are independently O, N, S, P, or B,

 wherein
n is 0-6; and
Y 1 is selected from the group consisting of —OR 1 , —NR 1 , —SR 1 , and —R 1 .

3. The compound of claim 1 , wherein the compound is selected from the group consisting of:

4. The compound of claim 1 , wherein the compound has the following formula:

wherein
Q is selected from the group consisting of —OH, —SH, —NR 1 ,

 wherein
E is selected from the group consisting of oxygen atom, sulfur atom, —N(R 1 )—, and —N(OR 1 )—;
R 1 is selected from the group consisting of H, substituted or unsubstituted C 1 -C 14 alkyl, substituted or unsubstituted C 1 -C 14 heteroalkyl, wherein 1-7 of the chain atoms are independently O, N, S, P, or B, substituted or unsubstituted C 1 -C 14 alkenyl, substituted or unsubstituted C 1 -C 14 heteroalkenyl, wherein 1-7 of the chain atoms are independently O, N, S, P, or B, substituted or unsubstituted C 1 -C 14 alkynyl, substituted or unsubstituted C 1 -C 14 heteroalkynyl, wherein 1-7 of the chain atoms are independently O, N, S, P, or B, substituted or unsubstituted C 5 -C 14 aryl, halo, heteroaryl having 5-14 ring atoms, wherein 1-8 of the ring atoms are independently O, N, S, P, or B,

 wherein
Y 1 is selected from the group consisting of —OR 1 , —NR 1 , —SR 1 , and —R 1 ;

A is selected from the group consisting of direct covalent bond, —SO 2 —NH—, —NH—; and
Z is selected from the group consisting of —S—, —O—, -ER 1 —, —CH, —N—, —NH—, —N + (R 1 )—, and —N(R 1 )—;

W is selected from the group consisting of —N(R 1 ) 2 , —NO 2 , -halogen,

wherein
X is —N—, or —C(R 1 )—; and
Y is selected from the group consisting of —R 1 , -ER 1 , —X(R 1 ) 2 , and -halogen.

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

6. The compound of claim 1 , wherein the compound has the following formula:

wherein
R 1 is selected from the group consisting of H, substituted or unsubstituted C 1 -C 14 alkyl, substituted or unsubstituted C 1 -C 14 heteroalkyl, wherein 1-7 of the chain atoms are independently O, N, S, P, or B, substituted or unsubstituted C 1 -C 14 alkenyl, substituted or unsubstituted C 1 -C 14 heteroalkenyl, wherein 1-7 of the chain atoms are independently O, N, S, P, or B, substituted or unsubstituted C 1 -C 14 alkynyl, substituted or unsubstituted C 1 -C 14 heteroalkynyl, wherein 1-7 of the chain atoms are independently O, N, S, P, or B, substituted or unsubstituted C 5 -C 14 aryl, halo, heteroaryl having 5-14 ring atoms, wherein 1-8 of the ring atoms are independently O, N, S, P, or B,

 wherein
Y 1 is selected from the group consisting of —OR 1 , —NR 1 , —SR 1 , and —R 1 ;

W is selected from the group consisting of —R 1 , —OR 1 , —N(R 1 ) 2 , —NO 2 , -halogen,

Assignees

• Univ Maryland
• Univ Maryland

Inventors

• Sintim Herman O
• Zhou Jie
• Wang Changhao
• Lapidus Rena

Classifications

• C07D413/12

  linked by a chain containing hetero atoms as chain links · CPC title

• A61K31/4725

  containing further heterocyclic rings · CPC title

• C07C257/18

  having carbon atoms of amidino groups bound to carbon atoms of six-membered aromatic rings · CPC title

• C07D471/04

  Ortho-condensed systems · CPC title

• C07D417/12

  linked by a chain containing hetero atoms as chain links · CPC title