Antimicrobial compounds and methods of making and using the 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 (AA):
or a tautomer thereof or a pharmaceutically acceptable salt of the compound or tautomer, wherein:
J is selected from
X is selected from a 5- or 6-membered heterocyclyl ring and phenyl, wherein each of the 5- or 6-membered heterocyclyl ring and phenyl is optionally substituted with one or more R x ;
Z is selected from
each of R 1 , R 2 , and R 3 is independently selected from H and C 1-3 alkyl, provided that one or two of R 1 , R 2 , and R 3 is H, and when two of R 1 , R 2 , and R 3 are H and the other is C 1-3 alkyl, or when one of R 1 , R 2 , and R 3 is H and the other two are C 1-3 alkyl;
or R 1 is Hand R 2 and R 3 together with the nitrogen atoms to which they are attached and the carbon atom connecting the two nitrogen atoms form a 5- or 6-membered ring;
R 4 is C 1-3 alkyl;
R 5 is selected from H and C 1-6 alkyl;
R 6 is selected from H, C 1-6 alkyl, C 2-6 alkenyl, and C 3-6 cycloalkyl, wherein the C 1-6 alkyl is optionally substituted with one or more substituents selected from the group consisting of halogen, OR a , SR a , —C(O)OR a , —SC(NH)NH 2 , C 3-6 cycloalkyl, and 3-6 membered heterocyclyl;
R 7 is selected from H and C 1-6 alkyl;
or R 6 and R 7 together with the carbon and nitrogen atoms to which they are attached form a ring having one of the formulas:
wherein the ring is optionally substituted on a ring carbon atom with C 1-6 alkyl, wherein the C 1-6 alkyl is optionally substituted with one or more OH;
or R 5 and R 7 together with the carbon atoms to which they are attached and the nitrogen atom connecting the two carbon atoms form a ring having one of the formulas:
wherein the ring is optionally substituted on a ring carbon atom with OH;
Q is selected from C 1-2 alkylene or —C(O)—;
R 21 is selected from H, C 1-6 alkyl optionally substituted with 1-3 halo;
R 8 is selected from H and halogen;
each R X is independently selected from halogen, C 1-6 alkyl, C 1-4 haloalkyl, OR C , N(R c ) 2 , —C(O)OR c , —C(O)R c , C 3-6 cycloalkyl, and aryl, wherein the C 1-6 alkyl is optionally substituted with one or more R b ,
or two adjacent R x come together with the atoms to which they are attached to form a 5- or 6-membered ring;
each R a is independently selected from H and C 1-6 alkyl;
each R b is independently selected from C 2-6 alkenyl, OR c , N(R c ) 2 , —C(O)OR c , C 3-6 cycloalkyl, OC(NH)NH 2 , and aryl;
each R c is independently selected from H, C 1-6 alkyl, aryl, —C(O) aryl, and —(CH 2 )aryl, wherein the C 1-6 alkyl and the aryl are each optionally substituted with one or more R d ; and
each R d is independently selected from C 1-3 alkyl, OH, O(C 1-3 alkyl), NO 2 , NH 2 , NH(C 1-3 alkyl), and N(C 1-3 alkyl) 2 .
2. The compound of claim 1 , wherein two of R 1 , R 2 , and R 3 are H, and the other is C 1-3 alkyl.
3. The compound of claim 1 , wherein two of R 1 , R 2 , and R 3 are H, and the other is methyl.
4. The compound of claim 1 , wherein one of R 1 , R 2 , and R 3 is H, and the other two are C 1-3 alkyl.
5. The compound of claim 1 , wherein one of R 1 , R 2 , and R 3 is H, and the other two are methyl.
6. The compound of claim 1 , wherein R 1 is H; and R 2 and R 3 together with the nitrogen atoms to which they are attached and the carbon atom connecting the two nitrogen atoms form a 5- or 6-membered ring.
7. The compound of claim 1 , wherein R 1 is H; and R 2 and R 3 together with the nitrogen atoms to which they are attached and the carbon atom connecting the two nitrogen atoms form an imidazoline.
8. The compound of claim 1 , wherein one of R 5 and R 7 is H and the other is C 1-6 alkyl.
9. The compound of claim 1 , wherein R 5 is H and R 7 is C 1-6 alkyl.
10. The compound of claim 1 , wherein R 5 and R 7 together with the carbon atoms to which they are attached and the nitrogen atom connecting the two carbon atoms form
11. The compound of claim 1 , wherein R 5 and R 7 together with the carbon atoms to which they are attached and the nitrogen atom connecting the two carbon atoms form
wherein the ring is optionally further substituted with C 1-6 alkyl, wherein the C 1-6 alkyl is optionally substituted with one or more OH.
12. The compound of claim 1 , wherein R 5 and R 7 together with the carbon atoms to which they are attached and the nitrogen atom connecting the two carbon atoms form
13. The compound of claim 1 , wherein R 5 and R 7 together with the carbon atoms to which they are attached and the nitrogen atom connecting the two carbon atoms form
14. The compound of claim 1 , wherein R 6 and R 7 together with the carbon atoms to which they are attached and the nitrogen atom connecting the two carbon atoms form
15. The compound of claim 1 , wherein R 6 and R 7 together with the carbon atoms to which they are attached and the nitrogen atom connecting the two carbon atoms form
16. The compound of claim 1 , wherein R 6 is selected from H and C 1-6 alkyl optionally substituted with one or more substituents selected from the group consisting of halogen and OR a .
17. The compound of claim 1 , wherein R 6 is H.