Imidazole and thiazole compositions for modifying biological signaling

• US 10,407,420 B2
• Filed: 05/09/2018
• Issued: 09/10/2019
• Est. Priority Date: 07/18/2014
• Status: Active Grant

• Current Assignee: Ohio University
• Original Assignee: Ohio University
• Inventors: Goetz, Douglas, Bergmeier, Stephen C., McMills, Mark C., Orac, Cina M.
• Primary Examiner(s): Mauro, John M
• Application Number:
  US15/975,321
• Publication Number:
  US 20180362521A1
• Time in Patent Office: 489 Days
• CPC Class Codes: A61K 31/155 Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
• CPC Class Codes: A61K 31/4166 having oxo groups directly attached to the heterocyclic ring, e.g. phenytoin
• CPC Class Codes: A61K 31/427 not condensed and containing further heterocyclic rings
• CPC Class Codes: A61K 31/428 condensed with carbocyclic rings
• CPC Class Codes: A61K 31/4439 containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole nicotine A61K31/465
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/10 Antimycotics
• CPC Class Codes: A61P 33/00 Antiparasitic agents
• CPC Class Codes: C07D 233/84 Sulfur atoms
• CPC Class Codes: C07D 277/16 Sulfur atoms
• CPC Class Codes: C07D 277/36 Sulfur atoms
• CPC Class Codes: C07D 277/84 Naphthothiazoles
• CPC Class Codes: C07D 405/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 413/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 417/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 417/06 linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 417/14 containing three or more hetero rings
• CPC Class Codes: Y02A 50/30 : Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

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

in which R¹ is chosen from C₁ to C₁₀ aliphatic or heteroaliphatic groups, optionally substituted with one or more aryl groups, substituted aryl groups, heteroaryl groups, substituted heteroaryl groups, or combination thereof; R² is chosen from aromatic moieties, substituted aromatic moieties, heteroaromatic moieties, substituted heteroaromatic moieties, and coumarin; R³ is chosen from —H, C₁ to C₁₀ 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 R² 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.

Claims

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

2. The composition of claim 1, wherein R² is a group Q².

3. The composition of claim 1, wherein R² is a group Q² 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 R² is a group Q² 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 R² is a group Q² 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 R² is a group Q² 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):

8. The composition of claim 7, wherein R² is a group Q².

9. The composition of claim 7, wherein R² is a group Q² 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 R² is a group Q² 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 R² is a group Q² 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 R² is a group Q² 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 R² is a group Q² selected from the group consisting of 2,4-dimethoxyphenyl, 2,5-dimethoxyphenyl, and 3,4-dimethoxyphenyl.

14. The composition of claim 7, wherein R² is selected from the group consisting of