# US 11,999,739 B2 · Antimicrobials methods of making and using the same

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- Number: US 11,999,739 B2
- Document ID: US11999739B2
- Status: Granted
- Kind: B2
- Application number: 17/409,286
- Filed: 2021-08-23
- Published: 2022-04-14
- Granted: 2024-06-04
- Earliest claimed: 2016-05-06
- Assignees: Bioversys AG
- Applicants: Bioversys AG
- Inventors: Erin M. Duffy; Ashoke Bhattacharjee; Zoltan F. Kanyo; Joseph A. Ippolito
- Web page: https://patentgrep.com/patent/US11999739B2

## CPC

- C07D 487/04: Ortho-condensed systems
- A61P 31/00: Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P 31/04: Antibacterial agents
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

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 tautomer thereof or a pharmaceutically acceptable salt of the compound or tautomer

## Claims

### Claim 1

A compound of Formula (II):
or a tautomer thereof or a pharmaceutically acceptable salt of the compound or tautomer wherein:
R1 is selected from the group consisting of H and halo;
R2 is selected from the group consisting of H, halo, C1-6 alkyl, C1-4 haloalkyl, and ORa1;
R3 is selected from the group consisting of H, C1-6 alkyl, C1-4 haloalkyl, and C(O)ORa1;
W is selected from the group consisting of N and CR4;
R5 is halo and R4 is selected from the group consisting of halo, S(C1-4 alkyl), and 6-membered heterocycloalkyl;
R6 is selected from the group consisting of H, C1-6 alkyl, C3-5 cycloalkyl, and C2-6 alkenyl wherein the C1-6 alkyl is optionally substituted with a substituent selected from the group consisting of ORa3, SRa3, and NRc3Rd3;
R7A is selected from the group consisting of H, C1-6 alkyl, C1-4 haloalkyl, and C2-6 alkenyl, wherein the C1-6 alkyl is optionally substituted with a substituent selected from the group consisting of ORa3 and SRa3;
R7B is H; or
R7A and R7B together with the carbon atom to which they are attached form a group selected from the group consisting of oxo, and C3-6 cycloalkyl; or
R6 and R7A together with the carbon atoms to which they are attached and the X atom connecting the two carbon atoms form a 5-to 6-membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O and S;
X is selected from the group consisting of O and NR8;
R8 is selected from the group consisting of H, C1-6 alkyl, and C1-4 haloalkyl, wherein the C1-6 alkyl is optionally substituted with R8A;
R8A is selected from the group consisting of 5-to 6-membered heteroaryl, and ORa3, wherein the 5-to 6-membered heteroaryl is optionally substituted with one or two C1-6 alkyl;
R9 is selected from the group consisting of H, C2-4 alkenyl, C1-4 haloalkyl and C1-4 alkyl optionally substituted with a substituent selected from the group consisting of amino, C1-4 alkoxy, C3-5 cycloalkyl, and 3- to 6-membered heterocycloalkyl;
R10 is selected from the group consisting of H and C2-6 alkenyl;
RA is selected from the group consisting of H and C1-6 alkyl;
L is selected from the group consisting of C1-6 alkyl and C2-6 alkenyl, wherein the C1-6 alkyl is optionally substituted with 1, 2, or 3 substituents independently selected from halo OR′, and SRa4;
R11 is selected from the group consisting of H, C1-6 alkyl, C3-5 cycloalkyl, C1-4 haloalkyl, and C2-6 alkenyl, wherein the C1-6 alkyl is optionally substituted with 1, 2, or 3 substituents independently selected from group consisting of CN, ORa5, SRa5, C(O)NRc5Rd5, Nc5Rd5 and S(O)2Rb5;
R12 is selected from the group consisting of H and C1-6 alkyl; or
R11 and R12 together with the carbon atom to which they are attached form a C3-5 cycloalkyl;
R13 is selected from the group consisting of H, halo, and C1-6 alkyl;
R14 is selected from the group consisting of H, halo, and C1-6 alkyl; and
RB is selected from the group consisting of H and C(═NRe5)Rb5; or
R11 and RB together with the carbon atom to which R11 is attached and the nitrogen atom to which RB is attached form a 5- to 6-membered heterocycloalkyl containing 1-3 heteroatoms selected from the group consisting of N, O and S, wherein the 5- to 6-membered heterocycloalkyl is optionally substituted with oxo;
each Ra1, Ra3, Ra4, Ra5, Rb5, Rc3, Rd3, Rc5, and Rd5 is independently selected from the group consisting of H, C1-6 alkyl, C1-4 haloalkyl, and 5-membered heteroaryl; and Re5 is selected from the group consisting of H and C1-4 alkyl.

### Claim 2 (depends on 1)

The compound of claim 1, wherein
R1 is halo; or
R1 is selected from the group consisting of H and fluoro; or
R1 is fluoro.

### Claim 3 (depends on 1)

The compound of claim 1, wherein R2 is selected from the group consisting of H, halo, C1-4 haloalkyl, and C1-4 haloalkoxy; or
R2 is selected from the group consisting of halo, C1-4 haloalkyl, and C1-4 haloalkoxy; or
R2 is selected from the group consisting of H, trifluoromethoxy, trifluoromethyl and chloro; or
R2 is selected from the group consisting of trifluoromethoxy, trifluoromethyl and chloro.

### Claim 4 (depends on 1)

The compound of claim 1, wherein
R1 is halo and R2 is halo; or
R1 is fluoro and R2 is chloro.

### Claim 5 (depends on 1)

The compound of claim 1, wherein
R3 is selected from the group consisting of H, C1-4 haloalkyl, and C(O)ORa1; or
R3 is selected from the group consisting of H, C1-4 haloalkyl, and C(O)C1-4 alkoxy; or
R3 is selected from the group consisting of H, trifluoromethyl, and C(═O)(methoxy); or
R3 is H.

### Claim 6 (depends on 1)

The compound of claim 1, wherein
R4 is selected from the group consisting of fluoro, chloro, methylthio, and N-morpholino.

### Claim 7 (depends on 1)

The compound of claim 1, wherein
R5 is F.

### Claim 8 (depends on 1)

The compound of claim 1, wherein
R5 is halo, and R4 is S(C1-4 alkyl); or
R5 is fluoro and R4 is selected from the group consisting of fluoro, methylthio and N-morpholino; or
R5 is fluoro and R4 is methylthio.

### Claim 9 (depends on 1)

The compound of claim 1, wherein
R6 is selected from the group consisting of H, C3-5 cycloalkyl, C2-6 alkenyl, C1-6 alkyl optionally substituted with a substituent selected from the group consisting of hydroxyl, C1-4 alkoxy, S(C1-4 alkyl), amino and NH(5-membered heteroaryl); or
R6 is selected from the group consisting of C3-5 cycloalkyl, C2-6 alkenyl, C1-6 alkyl optionally substituted with a substituent selected from hydroxyl, C1-4 alkoxy, S(C1-4 alkyl), amino, and NH(5-membered heteroaryl); or
R6 is selected from the group consisting of H, cyclopropyl, ethenyl, aminomethyl, hydroxymethyl, CH2NH-imidazole, methylthiomethyl, and methoxymethyl; or
R6 is selected from the group consisting of cyclopropyl, ethenyl, aminomethyl, hydroxymethyl, CH2NH-imidazole, methylthiomethyl, and methoxymethyl; or
R6 is H.

### Claim 10 (depends on 1)

The compound of claim 1, wherein
R7A is selected from the group consisting of H, C1-6 alkyl, C1-4 haloalkyl, C1-4 hydroxyalkyl, and C2-6 alkenyl; or
R7A is selected from the group consisting of C1-6 alkyl, C1-4 haloalkyl, C1-4 hydroxyalkyl, and C2-6 alkenyl; or
R7A is selected from the group consisting of H, methyl, trifluoromethyl, hydroxymethyl, difluoromethyl, and ethenyl; or
R7A is selected from the group consisting of methyl, trifluoromethyl, hydroxymethyl, difluoromethyl, and ethenyl; or
R7A is H.

### Claim 11 (depends on 1)

The compound of claim 1, wherein
R6 is selected from the group consisting of C2-6 alkenyl, C1-6 hydroxyalkyl, and C1-6 alkylene-NH(5-membered heteroaryl), and R7A is C1-6 alkyl; or
R6 is selected from the group consisting of ethenyl, hydroxymethyl, and CH2NH-imidazole, and R7A is C1-6 alkyl; or
R6 is H and R7A is C1-6 alkyl; or
R6 is H and R7A is methyl.

### Claim 12 (depends on 1)

The compound of claim 1, wherein R6 is H and R7A is methyl, and the carbon atom to which R7A is attached is in (5) configuration according to Cahn-Ingold-Prelog nomenclature.

### Claim 13 (depends on 1)

The compound of claim 1, wherein R6 is H and R7A is methyl, and the carbon to which R7A is attached is in (R) configuration according to Cahn-Ingold-Prelog nomenclature.

### Claim 14 (depends on 1)

The compound of claim 1, wherein
R6 and R7A together with the carbon atoms to which they are attached and the X atom connecting the two carbon atoms form a 6-membered heterocycloalkyl containing 1-3 heteroatoms selected from the group consisting of N, O and S; or
R6 and R7A together with the carbon atoms to which they are attached and the X atom connecting the two carbon atoms form a ring of any one of the following formulae:
or
R6 and R7A together with the carbon atoms to which they are attached and the X atom connecting the two carbon atoms form a ring of the following formulae:
wherein x indicates a point of attachment to the ring containing the W atom and substituted with R5; or
R6 and R7A together with the carbon atoms to which they are attached and the X atom connecting the two carbon atoms form a ring of any one of the following formulae:
or
R6 and R7A together with the carbon atoms to which they are attached and the X atom connecting the two carbon atoms form a ring of formula:
wherein x indicates a point of attachment to the ring containing the W atom and substituted with R5; or
R6 and R7A together with the carbon atoms to which they are attached and the X atom connecting the two carbon atoms form a ring of any one of the following formulae:
wherein x indicates a point of attachment to the ring containing the W atom and substituted with R5, or
R6 and R7A together with the carbon atoms to which they are attached and the X atom connecting the two carbon atoms form a ring of any one of the following formulae:
wherein x indicates a point of attachment to the ring containing the W atom and substituted with R5.

### Claim 15 (depends on 1)

The compound of claim 1, wherein
R8 is selected from the group consisting of H, C1-6 alkyl, C1-4 haloalkyl, C1-4 hydroxyalkyl, C1-6 alkyl substituted with C1-6 alkoxy, and C1-6 alkyl substituted with 5-to 6-membered heteroaryl, wherein the 5- to 6-membered heteroaryl is optionally substituted with 1 or 2 C1-6 alkyl; or
R8 is selected from the group consisting of H, methyl, 3-fluoropropyl, 2-methoxyethyl, 3-hydroxypropyl, 2-(pyridinyl)ethyl, 2-(imidazolyl)ethyl, (imidazolyl)methyl, and (oxazolyl)methyl, wherein each pyridinyl, imidazolyl, and oxazolyl is optionally substituted with 1 or 2 methyl; or
R8 is selected from the group consisting of any one of the following formulae:
or
R8 is selected from the group consisting of methyl, 3-fluoropropyl, 2-methoxyethyl, and 3-hydroxypropyl; or
R8 is H.

### Claim 16 (depends on 1)

The compound of claim 1, wherein
R9 is H; or
R9 is methyl.