# US 8,772,332 B2 · Arylpropionyl-alpha-pyrone antibacterial agents

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- Number: US 8,772,332 B2
- Document ID: US8772332B2
- Status: Granted
- Kind: B2
- Application number: 13/821,804
- Filed: 2011-09-07
- Published: 2013-11-07
- Granted: 2014-07-08
- Earliest claimed: 2010-09-09
- Applicants: Richard H. Ebright
- Inventors: Richard H. Ebright
- Web page: https://patentgrep.com/patent/US8772332B2

## CPC

- C07D 309/38: one oxygen atom in position 2 or 4, e.g. pyrones
- A61K 31/351: not condensed with another ring
- C07D 309/36: with oxygen atoms directly attached to ring carbon atoms
- 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
- 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)
- Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE

## Abstract

The invention provides a compound of formula (I): or a salt thereof, wherein R1-R4 have any of the values described in the specification, as well as compositions comprising a compound of formula (I). The compounds are useful as antibacterial agents.

## Claims

### Claim 1

A compound of formula I:
wherein:
R1 is one of aryl and heteroaryl, and optionally is substituted with one or more groups independently selected from halo, hydroxy, carboxy, cyano, nitro, trifluoromethyl, trifluoromethoxy, (C1-C6)alkyl, (C1-C6)alkoxy, (C1-C6)alkoxycarbonyl, (C1-C6)alkanoyloxy, aryl, heteroaryl, aryloxy, heteroaryloxy, and —NRaRb;
R2 is one of H, halo, hydroxy, carboxy, cyano, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkoxy, (C1-C6)alkoxycarbonyl, (C1-C6)alkanoyloxy, aryl, heteroaryl, aryloxy, heteroaryloxy, or —NRcRd, wherein any (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkoxy, (C1-C6)alkoxycarbonyl, (C1-C6)alkanoyloxy, aryl, and heteroaryl, and is optionally substituted with one or more halo, hydroxy, carboxy, cyano, nitro, (C1-C6)alkoxy, (C1-C6)alkoxycarbonyl, (C1-C6)alkanoyloxy or —NRcRd;
R3 is one of H, halo, hydroxy, carboxy, cyano, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkoxy, (C1-C6)alkoxycarbonyl, (C1-C6)alkanoyloxy, aryl, heteroaryl, aryloxy, heteroaryloxy, or —NReRf, wherein any (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkoxy, (C1-C6)alkoxycarbonyl, (C1-C6)alkanoyloxy, aryl, and heteroaryl, and is optionally substituted with one or more halo, hydroxy, carboxy, cyano, nitro, (C1-C6)alkoxy, (C1-C6)alkoxycarbonyl, (C1-C6)alkanoyloxy or —NReRf;
R4 is (C2-C6)alkyl or (C2-C6)alkenyl, which (C2-C6)alkyl or (C2-C6)alkenyl is optionally substituted with one or more groups independently selected from oxo, halo, hydroxy, carboxy, cyano, nitro, trifluoromethyl, trifluoromethoxy, (C1-C6)alkyl, (C1-C6)alkoxy, (C1-C6)alkoxycarbonyl, (C1-C6)alkanoyloxy, aryl, heteroaryl, aryloxy, heteroaryloxy, and —NRgRh;
Ra and Rb are each independently H, (C1-C6)alkyl, aryl, heteroaryl, aryl(C1-C6)alkyl, or heteroaryl(C1-C6) alkyl; or Ra and Rb together with the nitrogen to which they are attached form a morpholino, piperazino, pyrrolidino or piperidino;
Rc and Rd are each independently H, (C1-C6)alkyl, aryl, heteroaryl, aryl(C1-C6)alkyl, or heteroaryl(C1-C6) alkyl; or Rc and Rd together with the nitrogen to which they are attached form a morpholino, piperazino, pyrrolidino or piperidino;
Re and Rf are each independently H, (C1-C6)alkyl, aryl, heteroaryl, aryl(C1-C6)alkyl, or heteroaryl(C1-C6) alkyl; or Re and Rf together with the nitrogen to which they are attached form a morpholino, piperazino, pyrrolidino or piperidino; and
Rg and Rh are each independently H, (C1-C6)alkyl, aryl, heteroaryl, aryl(C1-C6)alkyl, or heteroaryl(C1-C6) alkyl; or Rg and Rh together with the nitrogen to which they are attached form a morpholino, piperazino, pyrrolidino or piperidino;
or a salt thereof.

### Claim 2 (depends on 1)

The compound of claim 1 wherein R2 is H or methyl; and R3 is H or methyl.

### Claim 3 (depends on 1)

The compound of claim 1 wherein R1 is phenyl which is optionally substituted with one or more groups independently selected from halo, hydroxy, carboxy, cyano, nitro, trifluoromethyl, trifluoromethoxy, (C1-C6)alkyl, (C1-C6)alkoxy, (C1-C6)alkoxycarbonyl, (C1-C6)alkanoyloxy, aryl, heteroaryl, aryloxy, heteroaryloxy, and —NRaRb.

### Claim 4 (depends on 1)

The compound of claim 1 wherein R1 is phenyl.

### Claim 5 (depends on 1)

The compound of claim 1 wherein R4 is n-butyl, or i-pentyl.

### Claim 6 (depends on 1)

The compound of claim 1 which is:
or a salt thereof.

### Claim 7 (depends on 1)

A composition comprising a compound of formula I as described in claim 1, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable vehicle.

### Claim 8 (depends on 1)

A method for inhibiting a bacterial RNA polymerase comprising contacting the bacterial RNA polymerase with a compound of formula I as described in claim 1, or a salt thereof.

### Claim 9 (depends on 1)

A method for inhibiting the growth of a bacterium comprising contacting the bacterium with a compound of formula I as described in claim 1, or a salt thereof.

### Claim 10 (depends on 1)

A method for treating a bacterial infection in a mammal comprising administering to the mammal an effective amount of a compound of formula I as described in claim 1, or a pharmaceutically acceptable salt thereof.

### Claim 11 (depends on 10)

The method of claim 10, wherein the bacteria is selected from Mycobacterium tuberculosis, Staphylococcus aureus MSSA and MRSA, Enterococcus faecalis, Enterococcus faecium, and Escherichia coli D21f21tolC.