Granted Patent B2

US 7,323,492 · App. 10/752,378 · Granted Jan 29, 2008

Abstract

Claims (58)

1. A compound of formula (I):

wherein:

A represents an aromatic 5 membered heterocycle, optionally containing, in addition to the nitrogen atom indicated in formula (I), one to three additional nitrogen atoms and optionally substituted by one or more groups R selected from

halogen,

—NRaRb,

C 1-6 alkyl,

C 2-6 alkenyl,

C 3-6 alkynyl,

aryl,

heteroaryl,

hydroxy,

—OC 1-6 alkyl,

formyl,

cyano,

trifluoromethyl,

—CHNORa,

—CO 2 Ra,

—CONRaRb,

—NRaC(O)Ra,

—NRaC(O)ORa,

—OC(O)NRaRb,

—OC(O)Ra,

—OC(O)ORa,

or a C 1-6 alkyl group substituted by one or more groups selected from hydroxy,

—NRaRb,

—OC 1-6 alkyl,

—SRa,

—CHNORa,

—CO 2 Ra,

—CONRaRb,

—NRaC(O)Ra,

—NRaC(O)ORa,

—OC(O)NRaRb,

—OC(O)Ra,

—OC(O)ORa

X represents —NRxRy or —OC 1-6 alkyl optionally substituted by one or more groups selected from hydroxy, methoxy, halogen, amino and trifluoromethyl;

Ra and Rb independently represent hydrogen or C 1-6 alkyl;

R 1 represents hydrogen, C 1-6 alkyl or together R 1 and R 2 represent a CH 2 moiety;

R 2 represents hydrogen, —OC 1-6 alkyl, —O(O)C 1-6 alkyl or hydroxy;

R 3 represents hydrogen, hydroxy or together R 3 and R 1 represent a CH 2 moiety;

R 4 represents hydrogen, or C 1-6 alkyl, optionally substituted by one or more groups selected from hydroxy, methoxy, halogen, amino and trifluoromethyl;

Rx and Ry independently represent hydrogen, benzyl, C 3-6 cycloalkyl, C 3-6 alkenyl, C 3-6 alkynyl, C 1-6 alkyl optionally substituted by one or more groups selected from hydroxy, methoxy, halogen, NRaRb and trifluoromethyl, —C 1-6 alkylcycloalkyl, —C 1-6 alkylheterocycle, C 1-6 alkylamino and C 1-6 alkylthio or together Rx and Ry form a heterocycle;

and pharmaceutically acceptable salts thereof.

2. A method for the treatment of a bacterial infection in a subject, which comprises administering to the subject an effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof.

3. A pharmaceutical formulation comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable carriers.

4. The method of claim 2 , wherein said subject is a human.

5. The compound of claim 1 , wherein R 2 and R 3 is hydrogen.

6. The compound of claim 1 , wherein Ra and Rb are each methyl.

7. The compound of claim 1 , wherein A is substituted pyrrole, pyrazole, 1,2,3-triazole, 1,2,4-triazole or tetrazole.

8. The compound of claim 7 , wherein said A is substituted with ethoxycarbonyl, carboxaldehyde, cyano, dimethylaminomethyl, oxime or methyloxime.

9. The compound of claim 1 , wherein said compound is

10. The compound of claim 1 , wherein said compound is

11. The compound of claim 1 , wherein said compound is 4S-(4aα, 5aα,12aα)]-7-(1H-pyrrol-1-yl-3-carboxaldehyde)-4-(dimethylamino)-9-[[(N,N,-dimethylamino)acetyl]-amino]-1,4,4a,5,5a,6,11,12a-octahydro-3,10,12,12a-tetrahydroxy-1,11-dioxo-2-naphthacenecarboxamide, and pharmaceutically acceptable derivatives thereof.

12. The compound of claim 1 , wherein said compound is 4S-(4aα, 5aα,12aα)]-7-(1H-pyrrol-1-yl-3-carboxaldehyde)-4-(dimethylamino)-9-[[(N,N,-dimethylamino)acetyl]-amino]-1,4,4a,5,5a,6,11,12a-octahydro-3,10,12,12a-tetrahydroxy-1,11-dioxo-2-naphthacenecarboxamide and pharmaceutically acceptable derivatives thereof.

13. The method of claim 2 , wherein said bacterial infection is a gram negative or gram positive bacterial infection.

14. The method of claim 2 , wherein said bacterial infection is an infection of bacteria selected from the group consisting of S. pneumoniae, S. aureus, H. influenzae, M. catarrhalis , and E. coli.

15. The method of claim 2 , wherein said subject is treated for rickettesai, lymphogranuloma venereum, inclusion conjunctivitis or psittacosis.

16. The method of claim 2 , wherein said bacterial infection is an infection of bacteria selected from the group consisting of pneumococci, Salmonella , and E. faecalis.

Assignments (9)