Compositions and methods comprising substituted 2-aminoimidazoles

Patent metadata

Field	Value
Publication number	US-11339140-B2
Application number	US-201916586667-A
Country	US
Kind code	B2
Filing date	Sep 27, 2019
Priority date	Mar 31, 2017
Publication date	May 24, 2022
Grant date	May 24, 2022

Abstract

The present invention presents 2-(acylamino)imidazoles with therapeutic activity, including selective activity against cancer cells, and compositions comprising them. Methods of using and preparing the 2-(acylamino)imidazoles are also presented.

First claim

What is claimed is:

1. A composition for therapeutic use, the composition comprising a 2-(acylamino)imidazole compound of structure I:

or a salt, or a tautomer thereof;
wherein:
R 1 is haloaryl;
X is a bond;
Y is O;
R 2 is a member independently selected from the group consisting of alkyl, alkenyl, alkynyl, and arylalkyl; or, alternatively, R 2 and R 7 join to form an additional heterocyclyl fused ring;
R 4 is selected from the group consisting of:

wherein A 1 , A 2 , A 3 , A 4 , and A 5 are each independently selected CH or CR 6n ; and one, two, or three of A 1 , A 2 , A 3 , A 4 , and A 5 are optionally N;

wherein A 1 is NH; A 2 , A 3 , and A 4 are each independently selected CH or CR 6n ; and one, two, or three of A 2 , A 3 , and A 4 are optionally N;

wherein A 2 is NH; A 1 , A 3 , and A 4 are each independently selected CH or CR 6n ; and one, two, or three of A 1 , A 3 , and A 4 are optionally N;

wherein A 3 is NH; A 1 , A 2 , and A 4 are each independently selected CH or CR 6n ; and one, two, or three of A 1 , A 2 , and A 4 are optionally N;

wherein A 4 is NH; A 1 , A 2 , and A 3 are each independently selected CH or CR 6n ; and one, two, or three of A 1 , A 2 , and A 3 are optionally N;

each of the R 6n members is independently selected from the group consisting of alkyl, hydroxy, alkoxy, aminoalkoxy, alkylamino, alkylaminoalkoxy, alkenyl, alkynyl, aryl, aryloxy, arylamino, cycloalkyl, cycloalkylalkyl, cycloalkoxy, cycloalkylalkoxy, cycloalkylamino, cycloalkylalkylamino, heterocyclyl, heterocycyloxy, heterocycylalkyloxy, heterocycylamino, heterocycylalkylamino, halo, haloalkyl, fluoroalkyloxy, arylalkyl, arylalkyloxy, arylalkylamino, heteroaryl, heteroaryloxy, heteroarylamino, heteroarylalkyl, heteroarylalkyloxy, and heteroarylalkylamino; or, alternatively, a pair of adjacent R 6n members join to form an additional fused ring that is selected from the group consisting of cycloalkyl, aryl, heterocyclyl, and heterocycloaryl; and
R 7 is a member independently selected from the group consisting of hydrogen, halo, methyl, trifluoromethyl, ethyl, and isopropyl; or, alternatively, R 2 and R 7 join to form an additional heterocyclyl fused ring;
wherein the composition has <2% (w/w) of N 2 ,N 2 -diacylation; and
wherein the composition has <2% (w/w) of acyl regioisomers.

2. The composition of claim 1 , wherein the 2-aminoimidazole compound has <1% (w/w) of an impurity selected from the group consisting of

or a salt thereof.

3. The composition of claim 1 , wherein R 1 is a member selected from the group consisting of 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2,4-dichlorophenyl, 2-fluorophenyl, 3-fluorophenyl, and 4-fluorophenyl.

4. The composition of claim 1 , wherein R 1 is 4-chlorophenyl.

5. The composition of claim 1 , wherein R 2 is a member selected from the group consisting of alkyl, alkenyl, and arylalkyl.

6. The composition of claim 1 , wherein R 2 is methyl or ethyl.

7. The composition of claim 1 , wherein each of the R 6n members is independently selected from the group consisting of alkyl, hydroxy, alkoxy, cycloalkylalkoxy, halo, fluoroalkyl, fluoroalkyloxy, and arylalkyloxy.

8. The composition of claim 1 , wherein each of the R 6n members is independently selected from the group consisting of alkyl, hydroxy, and alkoxy.

9. The composition of claim 1 , wherein R 7 is methyl, isopropyl, or hydrogen.

10. The composition of claim 1 , wherein R 7 is hydrogen.

11. The composition of claim 1 , the composition comprising a compound that is selected from the group consisting of

and a salt thereof.

12. The composition of claim 1 , wherein the composition comprises the compound

or a salt thereof.

13. A method of treating breast cancer, the method comprising administering the composition of claim 1 to a patient with breast cancer, thereby treating the patient.

14. The method of claim 13 , wherein the composition comprises the compound

or a salt thereof.

Assignees

• Curza Global Llc
• Univ Utah Res Found
• The Univ Of Utah

Inventors

• Looper Ryan E
• Salvant Justin M
• Kirkeby Emily K
• Guo Wenxing
• Guillen Katrin P
• Welm Bryan E

Classifications

• C07D487/04

  Ortho-condensed systems · CPC title

• C07D405/04

  directly linked by a ring-member-to-ring-member bond · CPC title

• C07D401/04 Primary

  directly linked by a ring-member-to-ring-member bond · CPC title

• C07D233/88 Primary

  Nitrogen atoms, e.g. allantoin · CPC title

• A61P35/00

  Antineoplastic agents · CPC title