Pyrimidine derivatives for prevention and treatment of gram-negative bacterial infection, contamination and fouling

A method for killing or preventing Gram-negative bacterial growth in biofilm formation comprising applying on a surface of a medical device, an effective amount of pyrimidine derivatives represented by formula (I) together with a membrane penetrating agent:

• wherein:
• X1 and X2 are independently N, CH, or CR8 wherein R8 is C1-6 alkyl, C2-6 alkenyl or C2-6 alkynyl;
• with the exception that if one of X1 or X2 is equal to N, then the remaining of X1 or X2 are selected from CH, CR8;
• —Y— is —O— or —S—;
• R1 and R2 are independently C1-6-alkyl, C2-6-alkenyl, C2-6-alkynyl, C3-6-cycloalkyl, aryl, or aryl-C1-6-alkyl wherein the alkyl or cycloalkyl moiety is optionally mono or polysubstituted with OH or an halogen and the aryl moiety is optionally mono or polysubstituted with an halogen, —C1-6 alkyl, —C1-6alkoxy, —OH, —NO2, —CN, —NH2, —NHR8, —N(R8)2—COOH, —COOR8, —CONH2, —CONHR8, —CON(R8)2, —SO2NH2, —SO2NHR8, or —SO2N(R8)2;
• R3, R4, R5, R6 and R7 are independently H, an halogen, a C1-6alkyl, C1-6alkoxy, —OH, —NO2, —CN, —NH2, —NHR8, —N(R8)2—COOH, —COOR8, —CONH2, —CONHR8, —CON(R8)2, —SO2NH2, —SO2NHR8, or —SO2N(R8)2, wherein said method is not a method of treatment of the human or animal body.

A method of diagnosing or prognosing a Gram-negative bacterial infection comprising using the pyrimidine derivative represented by formula (I) together with a membrane penetrating agent:

• wherein:
• X1 and X2 are independently N, CH, or CR8 wherein R8 is C1-6 alkyl, C2-6 alkenyl or C2-6 alkynyl;
• with the exception that if one of X1 or X2 is equal to N, then the remaining of X1 or X2 are selected from CH or CR8;
• —Y— is —O— or —S—;
• R1 and R2 are independently C1-6-alkyl, C2-6-alkenyl, C2-6-alkynyl, C3-6-cycloalkyl, aryl, aryl-C1-6-alkyl wherein the alkyl or cycloalkyl moiety is optionally mono or polysubstituted with OH or an halogen and the aryl moiety is optionally mono or polysubstituted with an halogen, —C1-6 alkyl, —C1-6alkoxy, —OH, —NO2, —CN, —NH2, —NHR8, —N(R8)2—COOH, —COOR8, —CONH2, —CONHR8, —CON(R8)2, —SO2NH2, —SO2NHR8, or —SO2N(R8)2;
• R3, R4, R5, R6 and R7 are independently H, an halogen, a C1-6alkyl, C1-6alkoxy, —OH, —NO2, —CN, —NH2, —NHR8, —N(R8)2—COOH, —COOR8, —CONH2, —CONHR8, —CON(R8)2, —SO2NH2, —SO2NHR8, or —SO2N(R8)2;
• and
• wherein the pyrimidine derivative comprises a detectable marker.