Cyanopyridine antibacterial agents and methods of use thereof
The present invention relates generally to compounds providing antibacterial therapeutic agents and preparations, and related methods of using and making antibacterial compounds. Antibacterial compounds of the present invention include chalcone, alkylpyrimidine, aminopyrimidine and cyanopyridine compounds and derivatives thereof exhibiting minimum inhibitory concentrations (MIC) similar to or less than conventional antibacterial compounds in wide use. For example, the present invention provides chalcone and cyanopyridine compounds, and derivatives thereof, exhibiting high antibacterial activities having multiple electron withdrawing group substituents, such as halogens and fluorinated alky groups, and optionally having hydroxyl and/or alkoxyl groups substituents.
1. A compound having the formula:
wherein
is selected from the group consisting of:
or a pharmaceutically acceptable salt thereof;
wherein each R 1 is independently selected from the group consisting of a hydrogen, and an unsubstituted C 1 -C 6 alkyl group;
wherein R 2 is selected from the group consisting of —H, —CH 3 , —CH 2 CH 3 , —CH 2 CH 2 CH 3 , —CH 2 CH 2 CH 2 CH 3 , —CH 2 CH 2 CH 2 CH 2 CH 3 , —OH, —OCH 3 , —OCH 2 CH 3 , —OCH 2 CH 2 CH 3 , —OCH 2 CH 2 CH 2 CH 3 and —OCH 2 CH 2 CH 2 CH 2 CH 3 ;
wherein R 6 is selected from the group consisting of —H, —CH 3 , —CH 2 CH 3 , —CH 2 CH 2 CH 3 , —CH 2 CH 2 CH 2 CH 3 , —CH 2 CH 2 CH 2 CH 2 CH 3 , —OH, —OCH 3 , —OCH 2 CH 3 , —OCH 2 CH 2 CH 3 , —OCH 2 CH 2 CH 2 CH 3 and —OCH 2 CH 2 CH 2 CH 2 CH 3 ;
and wherein at least one of R 2 and R 6 is —OH, —OCH 3 , —OCH 2 CH 3 , —OCH 2 CH 2 CH 3 , —OCH 2 CH 2 CH 2 CH 3 or —OCH 2 CH 2 CH 2 CH 2 CH 3 ;
wherein each R 3 is independently selected from the group consisting of a hydrogen, a halogen, an unsubstituted amine group, an unsubstituted C 1 -C 8 alkyl group, an unsubstituted C 1 -C 8 alkoxyl group, a C 1 -C 3 haloalkyl group, a hydroxyl group, a —CN group, an azide group, and a —NO 2 group;
wherein R 4 is selected from the group consisting of —F, —Cl, —Br, and —I;
wherein R 5 is selected from the group consisting of —CF 3 , —CF 2 CF 3 , —CF 2 CF 2 CF 3 , —CF 2 CF 2 CF 2 CF 3 , and —CF 2 CF 2 CF 2 CF 2 CF 2 CF 3 ;
wherein R 7 is an unsubstituted C 1 -C 8 alkyl group.
2. A compound of claim 1 having a formula selected from the group consisting of:
3. A compound of claim 2 :
wherein each R 1 is independently selected from the group consisting of —H, —CH 3 , —CH 2 CH 3 , —CH 2 CH 2 CH 3 and —CH 2 CH 2 CH 2 CH 3 ;
wherein each R 3 is independently selected from the group consisting of —H, —F, —Cl, —Br, —I, —CF 3 , —CF 2 CF 3 , —CF 2 CF 2 CF 3 , —CH 3 , —CH 2 CH 3 , —CH 2 CH 2 CH 3 , —CH 2 CH 2 CH 2 CH 3 , —OH, —OCH 3 , —OCH 2 CH 3 and —OCH 2 CH 2 CH 2 CH 3 ; and
wherein R 7 is selected from the group consisting of —CH 3 , —CH 2 CH 3 , —CH 2 CH 2 CH 3 , and —CH 2 CH 2 CH 2 CH 3 .
4. A compound of claim 1 having a formula selected from the group consisting of:
5. A pharmaceutical composition comprising a therapeutically effective amount of one or more compounds of claim 1 and a pharmaceutically acceptable carrier.
6. A compound of claim 1 having a formula selected from the group consisting of:
7. A compound of claim 6 wherein one of R 2 and R 6 is —OH, —OCH 3 , —OCH 2 CH 3 , —OCH 2 CH 2 CH 3 , —OCH 2 CH 2 CH 2 CH 3 or —OCH 2 CH 2 CH 2 CH 2 CH 3 and the other of R 2 and R 6 is —H, —CH 3 , —CH 2 CH 3 , —CH 2 CH 2 CH 3 , —CH 2 CH 2 CH 2 CH 3 , or —CH 2 CH 2 CH 2 CH 2 CH 3 .
8. A compound of claim 6 wherein R 2 is —OH, —OCH 3 , —OCH 2 CH 3 , —OCH 2 CH 2 CH 3 , —OCH 2 CH 2 CH 2 CH 3 or —OCH 2 CH 2 CH 2 CH 2 CH 3 and R 6 is —H, —CH 3 , —CH 2 CH 3 , —CH 2 CH 2 CH 3 , —CH 2 CH 2 CH 2 CH 3 , or —CH 2 CH 2 CH 2 CH 2 CH 3 .
9. A compound of claim 1 having a formula selected from the group consisting of:
10. A compound of claim 9 wherein one of R 2 and R 6 is —OH, —OCH 3 , —OCH 2 CH 3 , —OCH 2 CH 2 CH 3 , —OCH 2 CH 2 CH 2 CH 3 or —OCH 2 CH 2 CH 2 CH 2 CH 3 and the other of R 2 and R 6 is —H, —CH 3 , —CH 2 CH 3 , —CH 2 CH 2 CH 3 , —CH 2 CH 2 CH 2 CH 3 , or —CH 2 CH 2 CH 2 CH 2 CH 3 .
11. A compound of claim 9 wherein R 2 is —OH, —OCH 3 , —OCH 2 CH 3 , —OCH 2 CH 2 CH 3 , —OCH 2 CH 2 CH 2 CH 3 or —OCH 2 CH 2 CH 2 CH 2 CH 3 and R 6 is —H, —CH 3 , —CH 2 CH 3 , —CH 2 CH 2 CH 3 , —CH 2 CH 2 CH 2 CH 3 , or —CH 2 CH 2 CH 2 CH 2 CH 3 .
12. A compound of claim 11 having a formula selected from the group consisting of
13. A compound of claim 1 wherein:
each R 1 is independently selected from the group consisting of —H, —CH 3 , —CH 2 CH 3 , —CH 2 CH 2 CH 3 and —CH 2 CH 2 CH 2 CH 3 ;
R 2 is selected from the group consisting of —H, —CH 3 , —CH 2 CH 3 , —CH 2 CH 2 CH 3 , —CH 2 CH 2 CH 2 CH 3 , —CH 2 CH 2 CH 2 CH 2 CH 3 , —OH, —OCH 3 , —OCH 2 CH 3 , —OCH 2 CH 2 CH 3 , —OCH 2 CH 2 CH 2 CH 3 and —OCH 2 CH 2 CH 2 CH 2 CH 3 ;
each R 3 is independently selected from the group consisting of a hydrogen, a halogen, and an unsubstituted C 1 -C 8 alkyl group;
R 6 is selected from the group consisting of —H, —CH 3 , —CH 2 CH 3 , —CH 2 CH 2 CH 3 , —CH 2 CH 2 CH 2 CH 3 , —CH 2 CH 2 CH 2 CH 2 CH 3 , —OH, —OCH 3 , —OCH 2 CH 3 , —OCH 2 CH 2 CH 3 , —OCH 2 CH 2 CH 2 CH 3 and —OCH 2 CH 2 CH 2 CH 2 CH 3 ; and
R 7 is selected from the group consisting of —CH 3 , —CH 2 CH 3 , —CH 2 CH 2 CH 3 and —CH 2 CH 2 CH 2 CH 3 ;
wherein one of R 2 and R 6 is —OH, —OCH 3 , —OCH 2 CH 3 , —OCH 2 CH 2 CH 3 , —OCH 2 CH 2 CH 2 CH 3 and —OCH 2 CH 2 CH 2 CH 2 CH 3 ; and
the other of R 2 and R 6 is —H, —CH 3 , —CH 2 CH 3 , —CH 2 CH 2 CH 3 , —CH 2 CH 2 CH 2 CH 3 , or —CH 2 CH 2 CH 2 CH 2 CH 3 .
14. The compound of claim 13 wherein
each R 3 is independently selected from the group consisting of a hydrogen, a methyl group and a chlorine;
R 4 is chlorine; and
R 5 is —CF 3 .
15. The compound of claim 14 wherein
each R 1 is —H;
R 2 is —H, or —OH;
R 6 is —H, or —OH, and
R 7 is —CH 3 .
16. The compound of claim 13 having a formula selected from the group consisting of:
17. A compound of claim 16 wherein:
each R 1 is independently selected from the group consisting of —H, —CH 3 , —CH 2 CH 3 , —CH 2 CH 2 CH 3 and —CH 2 CH 2 CH 2 CH 3 ;
R 2 is selected from the group consisting of —H, —CH 3 , —CH 2 CH 3 , —CH 2 CH 2 CH 3 , —CH 2 CH 2 CH 2 CH 3 , —CH 2 CH 2 CH 2 CH 2 CH 3 , —OH, —OCH 3 , —OCH 2 CH 3 , —OCH 2 CH 2 CH 3 , —OCH 2 CH 2 CH 2 CH 3 and —OCH 2 CH 2 CH 2 CH 2 CH 3 ;
each R 3 is independently selected from the group consisting of a hydrogen and an unsubstituted C 1 -C 3 alkyl group;
R 6 is selected from the group consisting of —H, —CH 3 , —CH 2 CH 3 , —CH 2 CH 2 CH 3 , —CH 2 CH 2 CH 2 CH 3 , —CH 2 CH 2 CH 2 CH 2 CH 3 , —OH, —OCH 3 , —OCH 2 CH 3 , —OCH 2 CH 2 CH 3 , —OCH 2 CH 2 CH 2 CH 3 and —OCH 2 CH 2 CH 2 CH 2 CH 3 ; and
R 7 is —CH 3 ;
wherein one of R 2 and R 6 is —OH, —OCH 3 , —OCH 2 CH 3 , —OCH 2 CH 2 CH 3 , —OCH 2 CH 2 CH 2 CH 3 or —OCH 2 CH 2 CH 2 CH 2 CH 3 and the other of R 2 and R 6 is —H, —CH 3 , —CH 2 CH 3 , —CH 2 CH 2 CH 3 , —CH 2 CH 2 CH 2 CH 3 , or —CH 2 CH 2 CH 2 CH 2 CH 3 .
18. The compound of claim 16 wherein
each R 1 is —H;
R 2 is —H, or —OH;
R 6 is —H, or —OH, and
R 7 is —CH 3 .
19. A compound of claim 1 having a formula selected from the group consisting of:
20. A pharmaceutical composition comprising a therapeutically effective amount of one or more compounds of claim 19 and a pharmaceutically acceptable carrier.