# US 2019/0169114 A1 · Benzoylglycine Derivatives and Methods of Making and Using Same

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- Number: US 2019/0169114 A1
- Document ID: US20190169114A1
- Status: Published application
- Kind: A1
- Application number: 16/270,291
- Filed: 2019-02-07
- Published: 2019-06-06
- Earliest claimed: 2016-04-25
- Assignees: Duke University; The University of North Carolina at Chapel Hill
- Applicants: Duke University; The University of North Carolina at Chapel Hill
- Inventors: Pei Zhou; Eric J. Toone; Robert A. Nicholas; Ramesh Gopalaswamy; Xiaofei Liang; Frank Navas, III
- Web page: https://patentgrep.com/patent/US20190169114A1

## CPC

- C07C 259/06: having carbon atoms of hydroxamic groups bound to hydrogen atoms or to acyclic carbon atoms
- A61P 31/04: Antibacterial agents
- C07C 237/34: having the nitrogen atom of the carboxamide group bound to an acyclic carbon atom of a hydrocarbon radical substituted by nitrogen atoms not being part of nitro or nitroso groups
- C07C 237/36: having the nitrogen atom of the carboxamide group bound to an acyclic carbon atom of a hydrocarbon radical substituted by carboxyl groups
- C07C 259/18: having carbon atoms of hydroxamidine groups bound to carbon atoms of six-membered aromatic rings
- C07C 311/06: to acyclic carbon atoms of hydrocarbon radicals substituted by carboxyl groups
- C07C 317/06: of a saturated carbon skeleton containing rings
- C07C 317/18: with sulfone or sulfoxide groups bound to acyclic carbon atoms of the carbon skeleton
- C07C 317/44: having sulfone or sulfoxide groups and carboxyl groups bound to the same carbon skeleton
- C07D 203/08: with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring nitrogen atom
- C07D 203/18: by carboxylic acids, or by sulfur or nitrogen analogues thereof
- C07D 207/327: Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D 213/64: attached in position 2 or 6
- C07D 263/16: with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D 265/30: not condensed with other rings
- C07D 277/40: Unsubstituted amino or imino radicals
- C07D 295/10: substituted by doubly bound oxygen or sulphur atoms
- C07D 295/155: with the ring nitrogen atoms and the carbon atoms with three bonds to hetero atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
- C07D 309/04: with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D 309/10: Oxygen atoms
- C07D 335/02: not condensed with other rings
- C07H 15/203: Monocyclic carbocyclic rings other than cyclohexane rings; Bicyclic carbocyclic ring systems
- C07C 2601/02: with a three-membered ring
- C07C 2601/08: the ring being saturated
- C07C 2601/14: The ring being saturated
- 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
- C07C: ACYCLIC OR CARBOCYCLIC COMPOUNDS
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- C07H: SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS (derivatives of aldonic or saccharic acids C07C, C07D; aldonic acids, saccharic acids C07C59/105, C07C59/285; cyanohydrins C07C255/16; glycals C07D; compounds of unknown constitution C07G; polysaccharides, derivatives thereof C08B; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification C12N15/00; sugar industry C13)
- Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE

## Abstract

Disclosed are compounds of formulae: and pharmaceutically acceptable salts thereof, wherein the variables, R1, R2, R3, R4, R5, R6, R7, R11, R12, R13, R14, R15, R16, R17, n, and m are defined herein. These compounds are useful for treating Gram-negative bacteria infections. Also disclosed are methods of making these compounds.

## Claims

### Claim 1

A compound which is
4-(cyclopropylbuta-1,3-diyn-1-yl)-N-((2S,3S)-4,4-difluoro-3-hydroxy-1-(hydroxyamino)-3-methyl-1-oxobutan-2-yl)benzamide;
N-((2S,3S)-4,4-difluoro-3-hydroxy-1-(hydroxyamino)-3-methyl-1-oxobutan-2-yl)-4-((2-(hydroxymethyl)cyclopropyl)buta-1,3-diyn-1-yl)benzamide;
4-((2-(aminomethyl)cyclopropyl)buta-1,3-diyn-1-yl)-N-((2S,3S)-4,4-difluoro-3-hydroxy-1-(hydroxyamino)-3-methyl-1-oxobutan-2-yl)benzamide;
N-((2S,3S)-4,4-difluoro-3-hydroxy-1-(hydroxyamino)-3-methyl-1-oxobutan-2-yl)-4-((2-(methylsulfonamidomethyl)cyclopropyl)buta-1,3-diyn-1-yl)benzamide;
N-((2S,3S)-4,4-difluoro-3-hydroxy-1-(hydroxyamino)-3-methyl-1-oxobutan-2-yl)-4-((2-(methoxymethyl)cyclopropyl)buta-1,3-diyn-1l-yl)benzamide;
N-((2S,3S)-4,4-difluoro-3-hydroxy-1-(hydroxyamino)-3-methyl-1-oxobutan-2-yl)-4-((2-((methylamino)methyl)cyclopropyl)buta-1,3-diyn-1-yl)benzamide;
N-((2S,3S)-4,4-difluoro-3-hydroxy-1-(hydroxyamino)-3-methyl-1-oxobutan-2-yl)-4-((2-(2-oxopropyl)cyclopropyl)buta-1,3-diyn-1-yl)benzamide;
4-((2-(2-amino-2-oxoethyl)cyclopropyl)buta-1,3-diyn-1-yl)-N-((2S,3S)-4,4-difluoro-3-hydroxy-1-(hydroxyamino)-3-methyl-1-oxobutan-2-yl)benzamide;
4-((2-carbamoylcyclopropyl)buta-1,3-diyn-1-yl)-N-((2S,3S)-4,4-difluoro-3-hydroxy-1-(hydroxyamino)-3-methyl-1-oxobutan-2-yl)benzamide;
4-((2-acetylcyclopropyl)buta-1,3-diyn-1-yl)-N-((2S,3S)-4,4-difluoro-3-hydroxy-1-(hydroxyamino)-3-methyl-1-oxobutan-2-yl)benzamide;
or a pharmaceutically acceptable salt thereof.

### Claim 2 (depends on 1)

A pharmaceutical composition comprising a compound according to claim 1 and a pharmaceutically acceptable carrier, solvent, adjuvant or diluent.

### Claim 3 (depends on 1)

A method of treating Gram-negative bacterial infections, the method comprising administering to a subject in need of such treatment an effective amount of a compound according to claim 1.

### Claim 4 (depends on 3)

A method according to claim 3, wherein the Gram-negative bacteria is Pseudomonas aeruginosa, Stenotrophomonas maltophilia, Burkholderia cepacia, Alcaligenes xylosoxidans, Acinetobacter, Enterobacteriaceae, Haemophilus, Neisseria species, Francisella tularensis, Yersinia pestis, Burkholderia pseudomallei, Burkholderia mallei, Rickettsia prowazekii, Coxiella burnetti, Campylobacter jejuni, Shigella, Moraxella catarrhalis, or Chlamydia trachomatis.

### Claim 5 (depends on 3)

A method according to claim 3, wherein Enterobacteriaceae is selected from the group consisting of Serratia, Proteus, Klebsiella, Enterobacter, Citrobacter, Salmonella, Providencia, Morganella, Cedecea, Edwardsiella, Escherichia coli, Enterobacter cloacae, and Enterobacter aerogenes.

### Claim 6 (depends on 1)

A method of inhibiting a deacetylase enzyme in Gram-negative bacteria, the method comprising administering to a subject in need of such treatment an effective amount of a compound according to claim 1.

### Claim 7 (depends on 6)

A method according to claim 6, wherein deacetylase enzyme is LpxC.