# US 2019/0292199 A1 · Heterocyclic compounds useful as anti-bacterial agents and method for production

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- Number: US 2019/0292199 A1
- Document ID: US20190292199A1
- Status: Published application
- Kind: A1
- Application number: 16/301,887
- Filed: 2017-05-19
- Published: 2019-09-26
- Earliest claimed: 2016-05-20
- Assignees: Bugworks Research, Inc.
- Applicants: Bugworks Research, Inc.
- Inventors: SHAHUL HAMEED PEER MOHAMED; NAGAKUMAR BHARATHAM; NAINESH KATAGIHALLIMATH; SREEVALLI SHARMA; RADHA NANDISHAIAH
- Web page: https://patentgrep.com/patent/US20190292199A1

## CPC

- C07D 498/04: Ortho-condensed systems
- A61K 31/4439: containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole (nicotine A61K31/465)
- A61K 31/5383: ortho- or peri-condensed with heterocyclic ring systems
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 31/00: Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P 31/04: Antibacterial agents
- A61P 31/12: Antivirals
- C07D 413/14: containing three or more hetero rings
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The present disclosure relates to compounds of Formula I, its stereoisomers, pharmaceutically acceptable salts, complexes, hydrates, solvates, tautomers, polymorphs, racemic mixtures, optically active forms thereof and pharmaceutical compositions containing them as the active ingredient which can be used as medicaments. The aforementioned substances can also be used in the manufacture of medicaments for treatment, prevention or suppression of diseases, and conditions mediated by microbes. The present disclosure also relates to the synthesis and characterization of aforementioned substances.

## Claims

### Claim 1

A compound of Formula I
or stereoisomers, pharmaceutically acceptable salts, complexes, hydrates, solvates, tautomers, polymorphs, racemic mixtures, or optically active forms thereof, wherein
R1 is selected from the group consisting of hydrogen, C1-6 alkyl, C2-6 alkenyl, and C3-C6 cycloalkyl, each of which is unsubstituted or substituted with 1 to 3 groups independently selected from halogen, amino, hydroxy, oxetane, —OC1-6 alkyl, C3-6 cycloalkylamino, C1-6 alkylamino, or di(C1-6 alkyl)amino;
R2 is selected from the group consisting of hydrogen, hydroxyl, and amino;
X is —NH, —NC1-6 alkyl, O, or CR3R4;
R3 and R4 are independently selected from the group consisting of hydrogen, halogen, and C1-6 alkyl;
Y1 is N or CR5;
R5 is selected from the group consisting of hydrogen, halogen, cyano, —OC1-6 alkyl, —OC1-6 haloalkyl, and C1-6 alkyl;
Y2 is N or CH;
Y3 is N or CR6;
R6 is selected from the group consisting of hydrogen, halogen, cyano, C1-6 alkyl, —OC1-6 alkyl, and —OC1-6 haloalkyl;
Z1 is NH when Z2 is C1-6 alkylene; or Z1 is C1-6 alkylene when Z2 is NH;
n is 1 or 2;
W is CH2 wherein dotted line () represents no bond; W is O when dotted line () represents either a bond or no bond;
Ring A is selected from the group consisting of

### Claim 2 (depends on 1)

The compound of claim 1, or its stereoisomers, pharmaceutically acceptable salts, complexes, hydrates, solvates, tautomers, polymorphs, racemic mixtures, or optically active forms thereof,
wherein
R1 is selected from the group consisting of hydrogen, C1-6 alkyl, C2-6 alkenyl, and C3-6 cycloalkyl, wherein alkyl is optionally substituted with 1 to 3 groups independently selected from fluorine, hydroxy, amino, oxetane, —OC1 alkyl, C3-6 cycloalkylamino, C1-2 alkylamino, or di(C1-2 alkyl)amino;
R2 is selected from the group consisting of hydrogen, hydroxyl, and amino;
X is —NH, —NC1 alkyl, O, or CR3R4;
R3 and R4 are independently selected from the group consisting of hydrogen, fluorine, and C1 alkyl;
Y1 is N or CR5;
R5 is selected from the group consisting of hydrogen, fluorine, chlorine, cyano, —OCH3, —OCF3, OCHF2, and C alkyl;
Y2 is N or CH;
Y3 is N or CR6;
Re is selected from the group consisting of hydrogen, fluorine, cyano, —OCH3, —OCHF2, and —OCF3;
Z1 is NH when Z2 is CH2; or Z1 is CH2, CH2CH2 or CH(OH)CH2 when Z2 is NH;
n is 1 or 2
W is O when dotted line () represents either a bond or no bond;
Ring A is selected from the group consisting of

### Claim 3 (depends on 1)

The compound of claim 1 or stereoisomers, pharmaceutically acceptable salts, complexes, hydrates, solvates, tautomers, polymorphs, racemic mixtures, or optically active forms thereof, wherein the compound is selected from the group consisting of:
6-(5-(2-(((1-Methyl-2-oxoindolin-7-yl)methyl)amino)ethyl)-2-oxooxazolidin-3-yl)-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one,
6-(5-(2-(((6-Fluoro-1-methyl-2-oxoindolin-7-yl)methyl)amino)ethyl)-2-oxooxazolidin-3-yl)-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one,
6-(5-(2-(((6-Fluoro-1-methyl-2-oxoindolin-7-yl)methyl)amino)ethyl)-2-oxooxazolidin-3-yl)-2H-benzo[b][1,4]oxazin-3(4H)-one,
6-(5-(2-(((6-Fluoro-1,3,3-trimethyl-2-oxoindolin-7-yl)methyl)amino)ethyl)-2-oxooxazolidin-3-yl)-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one,
5-(5-(2-(((6-Fluoro-1-methyl-2-oxoindolin-7-yl)methyl)amino)ethyl)-2-oxooxazolidin-3-yl)-2-methylnicotinonitrile,
6-(5-(3-(((6-Fluoro-1-methyl-2-oxoindolin-7-yl)methyl)amino)propyl)-2-oxooxazolidin-3-yl)-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one,
6-(5-(2-(((1-Ethyl-6-fluoro-2-oxoindolin-7-yl)methyl)amino)ethyl)-2-oxooxazolidin-3-yl)-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one,
6-(5-(3-(((1-Ethyl-6-fluoro-2-oxoindolin-7-yl)methyl)amino)propyl)-2-oxooxazolidin-3-yl)-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one,
6-(5-(3-(((6-Fluoro-1-methyl-2-oxoindolin-7-yl)methyl)amino)propyl)-2-oxooxazolidin-3-yl)-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one (Enantiomer1),
6-(5-(3-(((6-Fluoro-1-methyl-2-oxoindolin-7-yl) methyl)amino)propyl)-2-oxooxazolidin-3-yl)-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one (Enantiomer2),
6-(5-(2-((2-(6-Fluoro-1-methyl-2-oxoindolin-7-yl)ethyl)amino)ethyl)-2-oxooxazolidin-3-yl)-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one,
6-(5-(3-(((6-Fluoro-1-methyl-2-oxoindolin-7-yl)methyl)amino)propyl)-2-oxooxazolidin-3-yl)-2H-benzo[b][1,4]oxazin-3(4H)-one,
6-(5-(2-((2-(6-Fluoro-1-methyl-2-oxoindolin-7-yl)ethyl)amino)ethyl)-2-oxooxazolidin-3-yl)-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one (Enantiomer1),
6-(5-(2-((2-(6-Fluoro-1-methyl-2-oxoindolin-7-yl)ethyl)amino)ethyl)-2-oxooxazolidin-3-yl)-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one (Enantiomer2),
6-(5-(2-((2-(6-Fluoro-1-methyl-2-oxoindolin-7-yl)-2-hydroxyethyl)amino)ethyl)-2-oxooxazolidin-3-yl)-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one,
6-(5-(2-((2-(5-Fluoro-3-methyl-2-oxo-2,3-dihydrobenzo[d]oxazol-4-yl)ethyl)amino)ethyl)-2-oxooxazolidin-3-yl)-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one, and
6-(5-(3-(((6-Fluoro-1-methyl-2-oxo-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-7-yl)methyl)amino)propyl)-2-oxooxazolidin-3-yl)-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one.

### Claim 4 (depends on 1)

A method for the preparation of compound of Formula I of claim 1 or stereoisomers, pharmaceutically acceptable salts, complexes, hydrates, solvates, tautomers, polymorphs, racemic mixtures, or optically active forms thereof.

### Claim 5 (depends on 1)

A pharmaceutical composition comprising a compound of Formula I of claim 1 or stereoisomers, pharmaceutically acceptable salts, complexes, hydrates, solvates, tautomers, polymorphs, racemic mixtures, or optically active forms thereof, wherein the pharmaceutical composition is formulated to deliver an effective amount of the compound as a medicament to a patient in need thereof.

### Claim 6 (depends on 5)

The pharmaceutical composition of claim 5, wherein the compound is effective in killing or inhibiting the growth of a microorganism selected from Gram positive and Gram negative bacteria.

### Claim 7 (depends on 5)

The pharmaceutical composition of claim 5, wherein the compound is effective in reducing a bacterial infection, in a patient, caused by Gram-positive bacteria or Gram-negative bacteria.

### Claim 8 (depends on 1)

A method for reducing a bacterial infection in a subject by administering an effective amount of a compound as claimed in claim 1.

### Claim 9 (depends on 8)

The method as claimed in claim 8, wherein the bacterial infection is caused by Gram-positive bacteria or Gram-negative bacteria.

### Claim 10 (depends on 9)

The method as claimed in claim 9, wherein the bacterial infection is caused by E. coli, P. aeruginasa, K. pneumonia, A. baumannii, S. aureus, E. faecalis, or E. faecium.

### Claim 11 (depends on 1)

The compound of claim 1 or stereoisomers, pharmaceutically acceptable salts, complexes, hydrates, solvates, tautomers, polymorphs, racemic mixtures, or optically active forms there, wherein the compound is effective in treating a disease or condition in a patient, wherein said disease or condition is caused by a microorganism selected from the group consisting of Gram positive and Gram negative bacteria.

### Claim 12 (depends on 1)

The compound of claim 1 or stereoisomers, pharmaceutically acceptable salts, complexes, hydrates, solvates, tautomers, polymorphs, racemic mixtures, or optically active forms thereof, wherein the compound is effective in in killing or inhibiting the growth of a microorganism selected from the group consisting of Gram positive and Gram negative bacteria.

### Claim 13 (depends on 5)

The pharmaceutical composition of claim 5, wherein the composition further comprises a pharmaceutically acceptable carrier.

### Claim 14 (depends on 5)

The pharmaceutical composition of claim 5, wherein the composition further comprises at least one antibiotic.

### Claim 15 (depends on 1)

A pharmaceutical composition comprising:
a compound of Formula I as claimed in claim 1;
a pharmaceutically acceptable carrier; and
at least one antibiotic.

### Claim 16 (depends on 1)

The compound of claim 1, wherein the Formula 1, or stereoisomers, pharmaceutically acceptable salts, complexes, hydrates, solvates, tautomers, polymorphs, racemic mixtures, or optically active forms thereof, are pharmaceutically active.