Imidazole and thiazole compositions for modifying biological signaling

Patent metadata

Field	Value
Publication number	US-10407420-B2
Application number	US-201815975321-A
Country	US
Kind code	B2
Filing date	May 9, 2018
Priority date	Jul 18, 2014
Publication date	Sep 10, 2019
Grant date	Sep 10, 2019

Abstract

Compounds having General Formula (I) or General Formula (II):

in which R 1 is chosen from C 1 to C 10 aliphatic or heteroaliphatic groups, optionally substituted with one or more aryl groups, substituted aryl groups, heteroaryl groups, substituted heteroaryl groups, or combination thereof; R 2 is chosen from aromatic moieties, substituted aromatic moieties, heteroaromatic moieties, substituted heteroaromatic moieties, and coumarin; R 3 is chosen from —H, C 1 to C 10 aliphatic or heteroaliphatic groups, phenyl, or substituted phenyl, wherein the aliphatic or heteroaliphatic groups are optionally substituted with one or more phenyl groups, aryl groups, heteroaryl groups, substituted heteroaryl groups, or combination thereof, and wherein the aliphatic or heteroaliphatic groups are optionally bonded to R 2 to form a ring; X is S or O; and Y is S or NH, may be used in pharmaceutical compositions that modify of biological signaling processes or as reagents for biological assays.

First claim

What is claimed is:

1. A composition comprising at least one compound having General Formula (I) or General Formula (II):

or a pharmaceutically-acceptable salt or solvate thereof, in which:
R 1 is methyl;
R 2 is selected from the group consisting of Q 2 ,

Q 2 is

where exactly two or exactly three of R 7 , R 8 , R 9 , and R 10 are hydrogen and the remaining two or one of R 7 , R 8 , R 9 , and R 10 are independently, selected from the group consisting of methoxy, ethoxy, hydroxy, trifluoromethoxy, N-methylamino, (N,N)-dimethylamino, cyano, chloro, fluoro, and nitro, provided Q 2 is not 4-methoxyphenyl, 4-chlorophenyl, 4-fluorophenyl, 4-hydroxyphenyl, 3,4-dichlorophenyl, or 3-nitrophenyl; and
R 3 is selected from the group consisting of hydrogen, methyl, ethyl, n-propyl, isopropyl, butyl, 4-butenyl, phenyl, and 2-phenylethyl.

2. The composition of claim 1 , wherein R 2 is a group Q 2 .

3. The composition of claim 1 , wherein R 2 is a group Q 2 selected from the group consisting of 2-methoxyphenyl, 3-methoxyphenyl, 3-chlorophenyl, 2,5-dimethoxyphenyl, 2,4-dimethoxyphenyl, 3,4-dimethoxyphenyl, 2,4-dichlorophenyl, 2,4-difluorophenyl, 4-(dimethylamino)phenyl, 4-(trifluoromethoxy)phenyl, 4-cyanophenyl, 3-hydroxyphenyl, 2,4-dihydroxyphenyl, 2-hydroxy-5-chlorophenyl, and 2-methoxy-5-fluorophenyl.

4. The composition of claim 1 , wherein R 2 is a group Q 2 selected from the group consisting of 2-methoxyphenyl, 3-methoxyphenyl, 3-chlorophenyl, 2,5-dimethoxyphenyl, 2,4-dimethoxyphenyl, 3,4-dimethoxyphenyl, 2,4-dichlorophenyl, 2,4-difluorophenyl, 4-(dimethylamino)phenyl, 4-(trifluoromethoxy)phenyl, and 4-cyanophenyl.

5. The composition of claim 1 , wherein R 2 is a group Q 2 selected from the group consisting of 3-methoxyphenyl, 3-chlorophenyl, 2,5-dimethoxyphenyl, 2,4-dimethoxyphenyl, 3,4-dimethoxyphenyl, and 4-(trifluoromethoxy)phenyl.

6. The composition of claim 1 , wherein R 2 is a group Q 2 selected from the group consisting of 2,4-dimethoxyphenyl, 2,5-dimethoxyphenyl, and 3,4-dimethoxyphenyl.

7. A composition comprising at least one compound having General Formula (I):

or a pharmaceutically-acceptable salt or solvate thereof, in which:
R 1 is methyl;
R 2 is selected from the group consisting of Q 2 ,

Q 2 is

where exactly two or exactly three of R 7 , R 8 , R 9 , and R 10 are hydrogen and the remaining two or one of R 7 , R 8 , R 9 , and R 10 are independently selected from the group consisting of methoxy, ethoxy, hydroxy, trifluoromethoxy, N-methylamino, (N,N)-dimethylamino, cyano, chloro, fluoro, and nitro, provided Q 2 is not 4-methoxyphenyl, 4-chlorophenyl, 4-fluorophenyl, 4-hydroxyphenyl, 3,4-dichlorophenyl, or 3-nitrophenyl; and
R 3 is hydrogen.

8. The composition of claim 7 , wherein R 2 is a group Q 2 .

9. The composition of claim 7 , wherein R 2 is a group Q 2 selected from the group consisting of 2-methoxyphenyl, 3-methoxyphenyl, 3-chlorophenyl, 2,5-dimethoxyphenyl, 2,4-dimethoxyphenyl, 3,4-dimethoxyphenyl, 2,4-dichlorophenyl, 2,4-difluorophenyl, 4-(dimethylamino)phenyl, 4-(trifluoromethoxy)phenyl, 4-cyanophenyl, 3-hydroxyphenyl, 2,4-dihydroxyphenyl, 2-hydroxy-5-chlorophenyl, and 2-methoxy-5-fluorophenyl.

10. The composition of claim 7 , wherein R 2 is a group Q 2 selected from the group consisting of 2,5-dimethoxyphenyl, 2,4-dimethoxyphenyl, 3,4-dimethoxyphenyl, 2,4-dichlorophenyl, 2,4-difluorophenyl, 2,4-dihydroxyphenyl, 2-hydroxy-5-chlorophenyl, and 2-methoxy-5-fluorophenyl.

11. The composition of claim 7 , wherein R 2 is a group Q 2 selected from the group consisting of 2-methoxyphenyl, 3-methoxyphenyl, 3-chlorophenyl, 2,5-dimethoxyphenyl, 2,4-dimethoxyphenyl, 3,4-dimethoxyphenyl, 2,4-dichlorophenyl, 2,4-difluorophenyl, 4-(dimethylamino)phenyl, 4-(trifluoromethoxy)phenyl, and 4-cyanophenyl.

12. The composition of claim 7 , wherein R 2 is a group Q 2 selected from the group consisting of 3-methoxyphenyl, 3-chlorophenyl, 2,5-dimethoxyphenyl, 2,4-dimethoxyphenyl, 3,4-dimethoxyphenyl, and 4-(trifluoromethoxy)phenyl.

13. The composition of claim 7 , wherein R 2 is a group Q 2 selected from the group consisting of 2,4-dimethoxyphenyl, 2,5-dimethoxyphenyl, and 3,4-dimethoxyphenyl.

14. The composition of claim 7 , wherein R 2 is selected from the group consisting of

Assignees

• Univ Ohio

Inventors

• Goetz Douglas
• Bergmeier Stephen C
• Mcmills Mark C
• Orac Cina M

Classifications

• A61P33/00

  Antiparasitic agents · CPC title

• A61P31/10

  Antimycotics · CPC title

• A61P31/04

  Antibacterial agents · CPC title

• A61P31/00

  Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics · CPC title

• A61P1/16

  for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics · CPC title