Antimicrobials and methods of making and using same
The present disclosure relates generally to the field of antimicrobial compounds and to methods of making and using them. These compounds are useful for treating, preventing, reducing the risk of, and delaying the onset of microbial infections in humans and animals. In some embodiments, the present disclosure provides a compound of Formula (I) or a tautomer thereof or a pharmaceutically acceptable salt of the compound or tautomer.
1. A compound of Formula (I):
or a tautomer thereof or a pharmaceutically acceptable salt of the compound or tautomer, wherein:
R 1 is selected from H and halo;
R 2 is selected from H, halo, C 1-6 alkyl, C 1-4 haloalkyl, and OR a1 ;
R 3 is selected from H, C 1-6 alkyl, and C 1-4 haloalkyl;
W is selected from N and CR 4 ;
R 4 is selected from H, halo, OR a2 , SR a2 , 5-6 membered heterocycloalkyl, C 1-6 alkyl, and C 2-6 alkenyl, wherein the C 1-6 alkyl is optionally substituted with a substituent selected from OR a2 ;
R 5 is selected from H, halo, C 1-6 alkyl, and C 2-6 alkenyl, wherein the C 1-6 alkyl is optionally substituted with a substituent selected from OR a2 ;
R 6 is selected from H, C 1-6 alkyl, and C 2-6 alkenyl, wherein said C 1-6 alkyl is optionally substituted with OR a3 ;
R 7 is selected from H and C 1-6 alkyl; or
R 6 and R 7 together with the carbon atoms to which they are attached and the nitrogen atom connecting said two carbon atoms form a ring of formula:
R 8 is selected from H, C 1-6 alkyl, and C 1-4 haloalkyl;
X is selected from 0 and NR N ;
R N is selected from H and C 1-4 alkyl;
R A is H;
R B is H; or
R A and R B together with the nitrogen atom to which they are attached form a 5- to 6-membered heterocycloalkyl ring containing 1 or 2 heteroatoms selected from N, O and S, wherein said 5- to 6-membered heterocycloalkyl is optionally substituted with halo;
R 9 is selected from C 1-6 alkyl, C 2-6 alkenyl, C 3-5 cycloalkyl, wherein said C 1-6 alkyl is optionally substituted with a substituent selected from OR a3 and SR a3 ;
R 10 is selected from H, C 2-4 alkenyl, C 1-4 haloalkyl and C 1-4 alkyl optionally substituted with a substituent selected from amino, C 1-4 alkoxy, C 3-5 cycloalkyl, and 3- to 6-membered heterocycloalkyl;
R 11 is H or C 1-3 alkyl, wherein the C 1-3 alkyl is optionally substituted with OH;
each R a1 , R a2 , and R a3 is independently selected from H, C 1-6 alkyl and C 1-4 haloalkyl.
2. A compound according to claim 1 , wherein
R 9 is selected from C 1-6 alkyl, C 3-5 cycloalkyl, wherein said C 1-6 alkyl is optionally substituted with a substituent selected from OR a3 and SR a3 ; and
R 11 is H.
3. The compound of claim 1 , wherein R 1 is selected from H and fluoro.
4. The compound of claim 1 , wherein R 2 is selected from H, halo, C 1-4 haloalkyl, and C 1-4 haloalkoxy.
5. The compound of claim 1 , wherein R 2 is selected from H, chloro, trifluoromethyl, and trifluoromethoxy.
6. The compound of claim 1 , wherein R 3 is selected from H, and C 1-4 haloalkyl.
7. The compound of claim 1 , wherein R 3 is selected from H, and trifluoromethyl.
8. The compound of claim 1 , wherein W is N.
9. The compound of claim 1 , wherein W is CR 4 .
10. The compound of claim 1 , wherein R 4 is selected from H, halo, C 1-6 alkyl, C 1-4 alkoxy, C 1-4 haloalkoxy, S(C 1-4 alkyl), and 6-membered heterocycloalkyl.
11. The compound of claim 1 , wherein R 4 is selected from halo, C 1-6 alkyl, C 1-4 alkoxy, C 1-4 haloalkoxy, S(C 1-4 alkyl), and 6-membered heterocycloalkyl.
12. The compound of claim 1 , wherein R 4 is selected from H, fluoro, chloro, methylthio, methoxy, methyl, trifluoromethoxy, and N-morpholino.
13. The compound of claim 1 , wherein W is CR 4 and R 4 is selected from H, halo, and S(C 1-6 alkyl).
14. The compound of claim 1 , wherein W is CR 4 and R 4 is selected from H, fluoro, and methylthio.
15. The compound of claim 1 , wherein R 5 is selected from H and fluoro.
16. The compound of claim 1 , wherein R 6 is selected from H, ethenyl, and C 1-6 hydroxyalkyl.
17. The compound of claim 1 , wherein R 6 is selected from H, ethenyl, and hydroxymethyl.
18. The compound of claim 1 , wherein R 7 is selected from H, and methyl.
19. The compound of claim 1 , wherein R 6 and R 7 form a ring of formula:
20. The compound of claim 1 , wherein R 6 and R 7 form a ring of formula:
wherein # indicates the ring carbon attached to the ring containing W.