Granted Patent B2

US 8,211,937 · App. 11/949,392 · Granted Jul 3, 2012

Abstract

Claims (57)

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 is 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,

and 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, and

—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, or C 1-6 alkyl;

R 2 represents hydroxy;

R 3 represents methyl;

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;

or a pharmaceutically acceptable salt 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, such that the tetracycline compound responsive state is treated.

3. A pharmaceutical formulation comprising a compound of claim 1 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 Ra and Rb are each methyl.

6. The compound of claim 1 , A represents pyrrole, pyrazole, 1,2,3-triazole, 1,2,4-triazole or tetrazole.

7. The compound of claim 1 , wherein R is ethoxycarbonyl, carboxaldehyde, cyano, dimethylaminomethyl, oxime or methyloxime.

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

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

10. The method of claim 2 , wherein the bacterial infection is infection of pneumococci.

11. The method of claim 2 , wherein the bacterial infection is infection of Salmonella.

12. The method of claim 2 , wherein the bacterial infection is infection of E. Coli.

13. The method of claim 2 , wherein the bacterial infection is infection of S. aureus.

14. The method of claim 2 , wherein the bacterial infection is infection of E. Faecalis.

Assignments (9)