Granted Patent B2

US 12,247,004 · App. 17/786,089 · Granted Mar 11, 2025

Inventors: Grace Edmund (London, GB); Michael H. Charlton (Oxford, GB); Paul William Finn (Faringdon, GB); Aigars Jirgensons (Riga, LV); Marija Skvorcova (Riga, LV); Janis Veliks (Riga, LV); Liene Grigorjeva (Riga, LV)

Assignee: Oxford Drug Design Limited

C07C381/10C07C313/06C07D213/71C07D215/36C07D231/18C07D277/16C07D307/79C07D317/50C07D333/34C07D333/52C07D495/04

Abstract

Claims (319)

1. A compound selected from compounds of the following formula, and pharmaceutically acceptable salts thereof:

wherein:

-A is independently -A C or -A H ;

-A C is independently phenyl or naphthyl, and is optionally substituted with one or more substituents —R X ;

-A H is independently C 5-12 heteroaryl, and is optionally substituted with one or more substituents —R X ;

and wherein:

each —R X is independently selected from:

—R XX , —R XXU , —R XXV ,

—F, —Cl, —Br, —I,

—OH, —OR XX ,

-L XX -OH, -L XX -OR XX ,

—CF 3 , —CHF 2 , —OCF 3 , —OCHF 2 ,

—NH 2 , —NHR XX , —NR XX 2 , —R XM ,

-L XX -NH 2 , -L XX -NHR XX , -L XX -NR XX 2 , -L XX -R XM ,

—C(═O)OH, —C(═O)OR XX , —OC(═O)R XX ,

—C(═O)NH 2 , —C(═O)NHR XX , —C(═O)NR XX 2 , —C(═O)R XM ,

—NHC(═O)R XX , —NR XN C(═O)R XX ,

—NHC(═O)NH 2 , —NHC(═O)NHR XX , —NHC(═O)NR XX 2 , —NHC(═O)R XM ,

—NR XN C(═O)NH 2 , —NR XN C(═O)NHR XX , —NR XN C(═O)NR XX 2 , —NR XN C(═O)R XM ,

—NHC(═O)OR XX , —NR XN C(═O)OR XX ,

—OC(═O)NH 2 , —OC(═O)NHR XX , —OC(═O)NR XX 2 , —OC(═O)R XM ,

—NHC(═NH)NH 2 ,

—C(═O)R XX ,

—S(═O)NH 2 , —S(═O)NHR XX , —S(═O)NR XX 2 , —S(═O)R XM ,

—S(═O) 2 NH 2 , —S(═O) 2 NHR XX , —S(═O) 2 NR XX 2 , —S(═O) 2 R XM ,

—NHS(═O)R XX , —NR XN S(═O)R XX ,

—NHS(═O) 2 R XX , —NR XN S(═O) 2 R XX ,

—S(═O)R XX , —S(═O) 2 R XX ,

—SH, —SR XX , —CN, and —NO 2 ;

and additionally, two adjacent groups —R X , if present, may together form:

—O—CH 2 —O—, —O—CH 2 CH 2 —O—, —CH 2 —CH 2 —O—, —CH 2 —CH 2 CH 2 —O—,

—CH 2 —O—CH 2 —, or —CH 2 —CH 2 —O—CH 2 —;

wherein:

each -L XX - is linear or branched saturated C 1-4 alkylene;

each —R XX is independently linear or branched saturated C 1-4 alkyl, phenyl, or —CH 2 -phenyl, wherein each phenyl is optionally substituted with one or more groups selected from —F, —Cl, —Br, -Me, —OH, —OMe, —CF 3 , and —OCF 3 ;

each —R XXU is independently linear or branched C 2-4 alkenyl;

each —R XXV is independently linear or branched C 2-4 alkynyl;

each —R XN is linear or branched saturated C 1-4 alkyl;

each —R XM is independently azetidino, pyrrolidino, piperidino, piperazino, morpholino, azepano, or diazepano, and is:

optionally substituted with one or more groups selected from:

—R XMM , —C(═O)R XMM , —C(═O)OR XMM , and —S(═O) 2 R XMM ;

wherein each —R XMM is independently linear or branched saturated C 1-4 alkyl, phenyl, or —CH 2 -phenyl, wherein each phenyl is optionally substituted with one or more groups selected from —F, —Cl, —Br, -Me, —OH, —OMe, —CF 3 , and —OCF 3 ;

—R 1 is independently —H or —R 11 ;

—R 11 is independently —R 11A or —R 11B ;

—R 11A is independently:

—R A1 , —R A2 , —R A3 , —R A4 , —R A5 , -L A -R A2 , -L A -R A3 , -L A -R A4 , or -L A -R A5 ;

each —R A1 is linear or branched saturated C 1-6 alkyl, and is optionally substituted with one or more groups —R AA2 ;

each —R A2 is saturated C 3-6 cycloalkyl, and is optionally substituted with one or more groups —R AA1 and one or more groups —R AA2 ;

each —R A3 is non-aromatic C 3-7 heterocyclyl, and is optionally substituted with one or more groups —R AA1 and one or more groups —R AA2 ;

each —R A4 is independently phenyl or naphthyl, and is optionally substituted with one or more groups —R AA1 and one or more groups —R AA2 ;

each —R A5 is C 5-10 heteroaryl, and is optionally substituted with one or more groups —R AA1 and one or more groups —R AA2 ;

each -L A - is linear or branched saturated C 1-4 alkylene;

each —R AA1 is independently selected from:

—R AA ,

-L AA -OH, -L AA -OR AA ,

-L AA -NH 2 , -L AA -NHR AA , -L AA -N(R AA ) 2 , and -L AA -R AM ;

each —R AA2 is independently selected from:

—F, —Cl, —Br, —I,

—OH, —OR AA ,

—CF 3 , —CHF 2 , —OCF 3 , —OCHF 2 ,

—NH 2 , —NHR AA , —N(R AA ) 2 , —R AM ,

—C(═O)OH, —C(═O)OR AA , —OC(═O)R AA ,

—C(═O)NH 2 , —C(═O)NHR AA , —C(═O)N(R AA ) 2 , —C(═O)R AM ,

—NHC(═O)R AA , —NR AN C(═O)R AA ,

—NHC(═O)NH 2 , —NHC(═O)NHR AA , —NHC(═O)N(R AA ) 2 , —NHC(═O)R AM ,

—NR AN C(═O)NH 2 , —NR AN C(═O)NHR AA , —NR AN C(═O)N(R AA ) 2 , —NR AN C(═O)R AM ,

—NHC(═O)OR AA , —NR AN C(═O)OR AA ,

—OC(═O)NH 2 , —OC(═O)NHR AA , —OC(═O)N(R AA ) 2 , —OC(═O)R AM ,

—NHC(═NH)NH 2 ,

—C(═O)R AA ,

—S(═O)NH 2 , —S(═O)NHR AA , —S(═O)N(R AA ) 2 , —S(═O)R AM ,

—S(═O) 2 NH 2 , —S(═O) 2 NHR AA , —S(═O) 2 N(R AA ) 2 , —S(═O) 2 R AM ,

—NHS(═O)R AA , —NR AN S(═O)R AA ,

—NHS(═O) 2 R AA , —NR AN S(═O) 2 R AA ,

—S(═O)R AA , —S(═O) 2 R AA ,

—SH, —SR AA , —CN, and —NO 2 ;

wherein:

each -L AA - is linear or branched saturated C 1-4 alkylene;

each —R AA is independently linear or branched saturated C 1-4 alkyl, phenyl, or —CH 2 -phenyl, wherein each phenyl is optionally substituted with one or more groups selected from —F, —Cl, —Br, -Me, —OH, —OMe, —CF 3 , and —OCF 3 ;

each —R AN is linear or branched saturated C 1-4 alkyl;

each —R AM is independently azetidino, pyrrolidino, piperidino, piperazino, morpholino, azepano, or diazepano, and is:

optionally substituted with one or more groups selected from:

—R AMM , —C(═O)R AMM , —C(═O)OR AMM , and —S(═O) 2 R AMM ;

wherein each —R AMM is independently linear or branched saturated C 1-4 alkyl, phenyl, or —CH 2 -phenyl, wherein each phenyl is optionally substituted with one or more groups selected from —F, —Cl, —Br, -Me, —OH, —OMe, —CF 3 , and —OCF 3 ;

—R 11B is independently selected from:

—F, —Cl, —Br, —I,

—OH, —OR BB ,

—CF 3 , —CHF 2 , —OCF 3 , —OCHF 2 ,

—NH 2 , —NHR BB , —NR BB 2 , —R BM ,

—C(═O)OH, —C(═O)OR BB , —OC(═O)R BB ,

—C(═O)NH 2 , —C(═O)NHR BB , —C(═O)NR BB 2 , —C(═O)R BM ,

—NHC(═O)R BB , —NR BN C(═O)R BB ,

—NHC(═O)NH 2 , —NHC(═O)NHR BB , —NHC(═O)NR BB 2 , —NHC(═O)R BM ,

—NR BN C(═O)NH 2 , —NR BN C(═O)NHR BB , —NR BN C(═O)NR BB 2 , —NR BN C(═O)R BM ,

—NHC(═O)OR BB , —NR BN C(═O)OR BB ,

—OC(═O)NH 2 , —OC(═O)NHR BB , —OC(═O)NR BB 2 , —OC(═O)R BM ,

—NHC(═NH)NH 2 ,

—C(═O)R BB ,

—S(═O)NH 2 , —S(═O)NHR BB , —S(═O)NR BB 2 , —S(═O)R BM ,

—S(═O) 2 NH 2 , —S(═O) 2 NHR BB , —S(═O) 2 NR BB 2 , —S(═O) 2 R BM ,

—NHS(═O)R BB , —NR BN S(═O)R BB ,

—NHS(═O) 2 R BB , —NR BN S(═O) 2 R BB ,

—S(═O)R BB , —S(═O) 2 R BB ,

—SH, —SR BB , —CN, and —NO 2 ;

wherein:

each —R BB is independently linear or branched saturated C 1-4 alkyl, phenyl, or —CH 2 -phenyl, wherein each phenyl is optionally substituted with one or more groups selected from —F, —Cl, —Br, -Me, —OH, —OMe, —CF 3 , and —OCF 3 ;

each —R BN is linear or branched saturated C 1-4 alkyl;

each —R BM is independently azetidino, pyrrolidino, piperidino, piperazino, morpholino, azepano, or diazepano, and is:

optionally substituted with one or more groups selected from:

—R BMM , —C(═O)R BMM , —C(═O)OR BMM , and —S(═O) 2 R BMM ;

wherein each —R BMM is independently linear or branched saturated C 1-4 alkyl, phenyl, or —CH 2 -phenyl, wherein each phenyl is optionally substituted with one or more groups selected from —F, —Cl, —Br, -Me, —OH, —OMe, —CF 3 , and —OCF 3 ;

—R 2 is independently —H or —R 22 ;

—R 22 is independently —R 22C or —R 22D ;

—R 22C is independently:

—R C1 , —R C2 , —R C3 , —R C4 , —R C5 , -L C -R C2 , -L C -R C3 , -L C -R C4 , or -L C -R C5 ;

each —R C1 is linear or branched saturated C 1-6 alkyl, and is optionally substituted with one or more groups —R CC2 ;

each —R C2 is saturated C 3-6 cycloalkyl, and is optionally substituted with one or more groups —R CC1 and one or more groups —R CC2 ;

each —R C3 is non-aromatic C 3-6 heterocyclyl, and is optionally substituted with one or more groups —R CC1 and one or more groups —R CC2 ;

each —R C4 is independently phenyl or naphthyl, and is optionally substituted with one or more groups —R CC1 and one or more groups —R CC2 ;

each —R C5 is C 5-10 heteroaryl, and is optionally substituted with one or more groups —R CC1 and one or more groups —R CC2 ;

each -L C - is linear or branched saturated C 1-4 alkylene;

each —R CC1 is independently selected from:

—R CC ,

-L CC -OH, -L CC -OR CC ,

-L CC -NH 2 , -L CC -NHR CC , -L CC -N(R CC ) 2 , and -L CC -R CM ;

each —R CC2 is independently selected from:

—F, —Cl, —Br, —I,

—OH, —OR CC ,

—CF 3 , —CHF 2 , —OCF 3 , —OCHF 2 ,

—NH 2 , —NHR CC , —N(R CC ) 2 , —R CM ,

—C(═O)OH, —C(═O)OR CC , —OC(═O)R CC ,

—C(═O)NH 2 , —C(═O)NHR CC , —C(═O)N(R CC ) 2 , —C(═O)R CM ,

—NHC(═O)R CC , —NR CN C(═O)R CC ,

—NHC(═O)NH 2 , —NHC(═O)NHR CC , —NHC(═O)N(R CC ) 2 , —NHC(═O)R CM ,

—NR CN C(═O)NH 2 , —NR CN C(═O)NHR CC , —NR CN C(═O)N(R CC ) 2 ,

—NR CN C(═O)R CM ,

—NHC(═O)OR CC , —NR CN C(═O)OR CC ,

—OC(═O)NH 2 , —OC(═O)NHR CC , —OC(═O)N(R CC ) 2 , —OC(═O)R CM ,

—NHC(═NH)NH 2 ,

—C(═O) R CC ,

—S(═O)NH 2 , —S(═O)NHR CC , —S(═O)N(R CC ) 2 , —S(═O)R CM ,

—S(═O) 2 NH 2 , —S(═O) 2 NHR CC , —S(═O) 2 N(R CC ) 2 , —S(═O) 2 R CM ,

—NHS(═O)R CC , —NR CN S(═O)R CC ,

—NHS(═O) 2 R CC , —NR CN S(═O) 2 R CC ,

—S(═O)R CC , —S(═O) 2 R CC ,

—SH, —SR CC , —CN, and —NO 2 ;

wherein:

each -L CC - is linear or branched saturated C 1-4 alkylene;

each —R CC is independently linear or branched saturated C 1-4 alkyl, phenyl, or —CH 2 -phenyl, wherein each phenyl is optionally substituted with one or more groups selected from —F, —Cl, —Br, -Me, —OH, —OMe, —CF 3 , and —OCF 3 ;

each —R CN is linear or branched saturated C 1-4 alkyl;

each —R CM is independently azetidino, pyrrolidino, piperidino, piperazino, morpholino, azepano, or diazepano, and is:

optionally substituted with one or more groups selected from:

—R CMM , —C(═O)R CMM , —C(═O)OR CMM , and —S(═O) 2 R CMM ;

wherein each —R CMM is independently linear or branched saturated C 1-4 alkyl, phenyl, or —CH 2 -phenyl, wherein each phenyl is optionally substituted with one or more groups selected from —F, —Cl, —Br, -Me, —OH, —OMe, —CF 3 , and —OCF 3 ;

—R 22D is independently selected from:

—F, —Cl, —Br, —I,

—OH, —OR DD ,

—CF 3 , —CHF 2 , —OCF 3 , —OCHF 2 ,

—NH 2 , —NHR DD , —NR DD 2 , —R DM ,

—C(═O)OH, —C(═O)OR DD , —OC(═O)R DD ,

—C(═O)NH 2 , —C(═O)NHR DD , —C(═O)NR DD 2 , —C(═O)R DM ,

—NHC(═O)R DD , —NR DN C(═O)R DD ,

—NHC(═O)NH 2 , —NHC(═O)NHR DD , —NHC(═O)NR DD 2 , —NHC(═O)R DM ,

—NR DN C(═O)NH 2 , —NR DN C(═O)NHR DD , —NR DN C(═O)NR DD 2 , —NR DN C(═O)R DM ,

—NHC(═O)OR DD , —NR DN C(═O)OR DD ,

—OC(═O)NH 2 , —OC(═O)NHR DD , —OC(═O)NR DD 2 , —OC(═O)R DM ,

—NHC(═NH)NH 2 ,

—C(═O)R DD ,

—S(═O)NH 2 , —S(═O)NHR DD , —S(═O)NR DD 2 , —S(═O)R DM ,

—S(═O) 2 NH 2 , —S(═O) 2 NHR DD , —S(═O) 2 NR DD 2 , —S(═O) 2 R DM ,

—NHS(═O)R DD , —NR DN S(═O)R DD ,

—NHS(═O) 2 R DD , —NR DN S(═O) 2 R DD ,

—S(═O)R DD , —S(═O) 2 R DD ,

—SH, —SR DD , —CN, and —NO 2 ;

wherein:

each —R DD is independently linear or branched saturated C 1-4 alkyl, phenyl, or —CH 2 -phenyl, wherein each phenyl is optionally substituted with one or more groups selected from —F, —Cl, —Br, -Me, —OH, —OMe, —CF 3 , and —OCF 3 ;

each —R DN is linear or branched saturated C 1-4 alkyl;

each —R DM is independently azetidino, pyrrolidino, piperidino, piperazino, morpholino, azepano, or diazepano, and is:

optionally substituted with one or more groups selected from:

—R DMM , —C(═O)R DMM , —C(═O)OR DMM , and —S(═O) 2 R DMM ;

wherein each —R DMM is independently linear or branched saturated C 1-4 alkyl, phenyl, or —CH 2 -phenyl, wherein each phenyl is optionally substituted with one or more groups selected from —F, —Cl, —Br, -Me, —OH, —OMe, —CF 3 , and —OCF 3 ;

or —R 1 and —R 2 , together with the carbon atom to which they are attached, form a saturated C 3-6 cycloalkyl or a non-aromatic C 3-7 heterocyclyl, and is optionally substituted with one or more groups —R CC2 ;

and wherein:

—R N1 is independently —H or —R N ;

—R N2 is independently —H or —R N ;

each —R N is independently linear or branched saturated C 1-6 alkyl, phenyl, or —CH 2 -phenyl, wherein each phenyl is optionally substituted with one or more groups selected from —F, —Cl, —Br, -Me, —OH, —OMe, —CF 3 , and —OCF 3 ; or

—R N1 and R N2 , taken together, form C 2-6 alkylene.

2. A compound according to claim 1 , wherein:

—R N1 is —H; and

—R N2 is —H.

3. A compound according to claim 2 , wherein:

—R 1 is —R 11 ;

—R 11 is —R 11A ;

—R 11A is —R A1 ; and

—R 2 is —H.

4. A compound according to claim 3 , wherein:

R 2 is —H; and

the compound is a compound selected from compounds of the following formula, and pharmaceutically acceptable salts thereof:

5. A compound according to claim 4 , wherein:

—R 1 is independently —CH(CH 3 )CH 2 CH 3 , —CH 2 CH(CH 3 ) 2 , or —CH(CH 3 ) 2 ; and

—R 2 is —H.

6. A compound according to claim 4 , wherein:

—R 1 is —CH 2 CH(CH 3 ) 2 ; and

—R 2 is —H.

7. A compound according to claim 3 , wherein:

-A C , if present, is phenyl or naphthyl, and is optionally substituted with 1, 2, or 3 substituents —R X ; and

-A H , if present, is furanyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, and is optionally substituted with one or more substituents —R X .

8. A compound according to claim 3 , wherein:

-A is -A C ; and

-A C is phenyl, and is optionally substituted with 1, 2, or 3 substituents —R X .

9. A compound according to claim 3 , wherein:

-A is -A H ; and

-A H is thien-2-yl, and is optionally substituted with one or more substituents —R X .

10. A compound according to claim 6 , wherein:

-A is -A H ; and

-A H is thien-2-yl, and is optionally substituted with one or more substituents —R X .

11. A compound according to claim 3 , wherein:

-A is -A H ; and

-A H is independently selected from:

wherein each —R X3 and —R X4 is independently as defined for —R X .

12. A compound according to claim 6 , wherein:

-A is -A H ; and

-A H is independently selected from:

wherein each —R X3 and —R X4 is independently as defined for —R X .

13. A compound according to claim 7 , wherein:

each —R X , if present, is independently selected from:

—R XX ,

—F, —Cl, —Br, —I,

—OH, —OR XX ,

—CF 3 , —CHF 2 , —OCF 3 , —OCHF 2 ,

—NH 2 , —NHR XX , —NR XX 2 , —R XM ,

—C(═O)OH, —C(═O)OR XX , —OC(═O)R XX ,

—C(═O)NH 2 , —C(═O)NHR XX , —C(═O)NR XX 2 , —C(═O)R XM ,

—NHC(═O)R XX , —NR XN C(═O)R XX ,

—C(═O)R XX ,

—S(═O)NH 2 , —S(═O)NHR XX , —S(═O)NR XX 2 , —S(═O)R XM ,

—S(═O) 2 NH 2 , —S(═O) 2 NHR XX , —S(═O) 2 NR XX 2 , —S(═O) 2 R XM ,

—NHS(═O)R XX , —NR XN S(═O)R XX ,

—NHS(═O) 2 R XX , —NR XN S(═O) 2 R XX ,

—S(═O)R XX , —S(═O) 2 R XX ,

—SR XX , —CN, and —NO 2 .

14. A compound according to claim 10 , wherein:

each —R X , if present, is independently selected from:

—R XX ,

—F, —Cl, —Br, —I,

—OH, —OR XX ,

—CF 3 , —CHF 2 , —OCF 3 , —OCHF 2 ,

—NH 2 , —NHR XX , —NR XX 2 , —R XM , and

—CN;

each —R XX , if present, is linear or branched saturated C 1-4 alkyl;

each —R XM , if present, is independently pyrrolidino, piperidino, piperazino, or morpholino, and is: optionally substituted with one or more groups selected from: —R XMM , —C(═O)R XMM , —C(═O)OR XMM , and —S(═O) 2 R XMM ; and

each —R XMM , if present, is linear or branched saturated C 1-4 alkyl.

15. A compound according to claim 11 , wherein:

each —R X , if present, is independently selected from:

—R XX ,

—F, —Cl, —Br, —I,

—OH, —OR XX ,

—CF 3 , —CHF 2 , —OCF 3 , —OCHF 2 ,

—NH 2 , —NHR XX , —NR XX 2 , —R XM , and

—CN;

each —R XX , if present, is linear or branched saturated C 1-4 alkyl;

each —R XM , if present, is independently pyrrolidino, piperidino, piperazino, or morpholino, and is: optionally substituted with one or more groups selected from: —R XMM , —C(═O)R XMM , —C(═O)OR XMM , and —S(═O) 2 R XMM ; and

each —R XMM , if present, is linear or branched saturated C 1-4 alkyl.

16. A compound according to claim 12 , wherein:

each —R X , if present, is independently selected from:

—R XX ,

—F, —Cl, —Br, —I,

—OH, —OR XX ,

—CF 3 , —CHF 2 , —OCF 3 , —OCHF 2 ,

—NH 2 , —NHR XX , —NR XX 2 , —R XM , and

—CN;

each —R XX , if present, is linear or branched saturated C 1-4 alkyl;

each —R XM , if present, is independently pyrrolidino, piperidino, piperazino, or morpholino, and is: optionally substituted with one or more groups selected from: —R XMM , —C(═O)R XMM , —C(═O)OR XMM and —S(═O) 2 R XMM ; and

each —R XMM , if present, is linear or branched saturated C 1-4 alkyl.

17. A compound according to claim 1 , which is selected from compounds of the following formulae, and pharmaceutically acceptable salts thereof:

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

19. A method of preparing a pharmaceutical composition comprising the step of mixing a compound according to claim 1 , and a pharmaceutically acceptable carrier or diluent.

20. A method of inhibiting bacterial aminoacyl-tRNA synthetase, in vitro or in vivo, comprising contacting the synthetase with an effective amount of a compound according to claim 1 .

21. A method of inhibiting bacterial aminoacyl-tRNA synthetase function in a cell, in vitro or in vivo, comprising contacting the cell with an effective amount of a compound according to claim 1 .

22. A method of treatment of a disorder of the human or animal body, comprising administering to a subject in need of treatment a therapeutically-effective amount of a compound according to claim 1 , wherein the disorder is a bacterial infection.

23. A method according to claim 22 , wherein the bacteria are:

Staphylococci, for example S. aureus;

Enterococci, for example E. faecalis;

Streptococci, for example S. pneumoniae;

Haemophilus , for example H. influenza;

Moraxella , for example M. catarrhalis;

Klebsiella , for example K. pneumoniae;

Acinetobacter , for example A. baumanii;

Pseudomonas , for example P. aeruginosa;

Proteus , for example P. mirabilis;

Neisseria , for example Neisseria gonorrhoeae;

Clostridioides, for example Clostridioides difficile;

Campylobacter , for example C. jejuni;

Salmonella , for example S. typhi;

Shigella , for example S. flexneri;

Enterobacter , for example E. cloacae;

Citrobacter , for example C. freundii;

Serratia , for example Serratia marcescens ; or

Escherichia , for example E. coli.

24. A method according to claim 22 ,

wherein the infection is:

a central nervous system infection;

an external ear infection;

an infection of the middle ear, including acute otitis media;

an infection of the cranial sinuses;

an eye infection;

an infection of the oral cavity, including an infection of the teeth, gums, or mucosa;

an upper respiratory tract infection;

a lower respiratory tract infection;

a genitourinary infection;

a urinary tract infection;

an intra-abdominal infection;

a gastrointestinal infection;

a gynecological infection;

septicemia,

a bone or joint infection;

a skin or skin structure infection;

bacterial endocarditis; or

a burn infection.

Assignments (1)

Continuity (2)

References Cited (14)