Regulation of nitric oxide release and biofilm development

A compound of the formula (I), or a salt thereof:

• wherein T is a bond or a bivalent hydrocarbon having between 1 and 6 carbon atoms, R2 and R3 are
• independently selected from:
• hydrogen, C3-C7 cycloalkyl, C3-C7 cycloalkenyl, (CH2)pOC(O)PhOC(O)C1-C6alkyl, (CH2)pOC(O)APhC1-C6alkyl, branched or straight chain C1-C20 alkyl, branched or straight chain C2-C20 alkenyl, branched or straight chain C2-C20 alkynyl, wherein the alkyl, alkenyl or alkynyl chains may optionally be interrupted by one or more groups/heteroatoms selected from O, S, NH, NH2+, and wherein the alkyl, alkenyl or alkynyl groups may optionally be substituted by one or more substituents selected from the group consisting of:
• halogen, cyano, COOH, (CH2)pC(O)OC1-C6alkyl, C(O)OC1-C6alkenyl, SO3H, SO2halogen, SO2NH2 NH2, NH3+, OH, SH, OC1-C6alkyl, OC2-C6alkenyl, OC2-C6alkynyl, aryl and heteroaryl, or alternatively R2 and R3, together with the nitrogen to which they are attached, form a 4-, 5-, 6-, 7- or 8-membered ring which may optionally contain 1, 2, 3, 4, 5 or 6 additional nitrogen atoms and may be saturated, unsaturated or partially unsaturated, and wherein the 4-, 5-, 6-, 7- or 8-membered ring may optionally be substituted by one or more substituents selected from the group consisting of:
• —C(O)C1alkylene-naphthyl-OC1-C6alkyl, —C(O)C1-C3alkylene-Ph-C(O)-Ph, —C(O)CH2O(CH2)pOCH3, —C(O)OPhNO2, —C(O)OPhNH2, —C(O)O(CH2)pChalogen3, —C(O)O(CH2O)pCH3, C1-C6-alkyl, C2-C6alkenyl, C2-C6alkynyl, —C(O)C1-C6alkyleneCOOC1-C6alkyl, —C(O)C1-C3alkylenePhC1-C6alkyl, —C(O)O-pyrrolidinyl-2,5-dione, —C(O)C1-C3alkylenePhC1-C6alkyl, —C(O)(CH2)pOC1-C6alkyl, —C(O)O(CH2)phalogen, —C(O)O(CH2)pPh, —(CH2)pSH, —SO2naphthyl-NC1-C6alkyl, —C(O)ONC1-C6alkyl, —(CH2)pOH, —C(O)PhOAc, —C(O)(CH2)pNHC(O)C1-C6alkyl, —C(O)NH2, —C(O)M, —C(O)NR4R5, —(CH2)pCH(OH)CHOH, halogen, cyano, —COOH, —C(O)O(CH2)pPh, —C(O)OC1-C6alkyl, —C(O)OC2-C6alkenyl, —C(O)OC2-C6alkynyl, —C(O)SC1-C6alkyl, —C(O)SC2-C6alkenyl, —C(O)SC2-C6alkynyl, —C(O)C1-C6alkyl, SO3H, SO2halogen, SO2phenyl, SO2NH2, SO2NR4R5, SO2PhNHCOC1-C6alkyl, NH2, OH, SH, OC1-C6alkyl, OC2-C6alkenyl, OC2-C6alkynyl, aryl and heteroaryl, and wherein A is a bivalent hydrocarbon radical having between 1 and 4 carbon atoms, p is a number between 0 and 4, R4 and R5 independently represent C1-C6alkyl and M is pyridyl, pyrimidinyl, pyrazinyl, phenyl or triazinyl;
• or
• wherein R2 and R3 are independently selected from:
• hydrogen, C5-C7 cycloalkyl, (CH2)pOC(O)PhOC(O)C1-C6alkyl, (CH2)pOC(O)APhC1-C6alkyl, branched or straight chain C1-C10 alkyl, branched or straight chain C2-C10 alkenyl and branched or straight chain C2-C10 alkynyl, wherein the alkyl, alkenyl or alkynyl chains may optionally be interrupted by between one and three groups/heteroatoms selected from O, S, NH and NH2+, and wherein the alkyl, alkenyl or alkynyl chains may optionally be substituted by between one and six substituents selected from the group consisting of:
• halogen, phenyl, ethoxy, methoxy, propoxy, COOH, (CH2)pCOOC1-C4alkyl, NH2, NH3+, OH and SH, and wherein A is a bivalent hydrocarbon radical having between 1 or 2 carbon atoms and p is 0, 1 or 2;
• or
• wherein R2 and R3 are independently selected from:
• hydrogen, C5-C7 cycloalkyl, branched or straight chain C1-C10 alkyl, branched or straight chain C2-C10 alkenyl, branched or straight chain C2-C10 alkynyl, wherein the alkyl, alkenyl or alkynyl chains may optionally be interrupted by between one and three groups selected from O, NH and NH2+, and wherein the alkyl, alkenyl or alkynyl chains may optionally be substituted by between one and four substituents selected from the group consisting of:
• halogen, phenyl, methoxy, COOH, CH2COOC1-C4alkyl, NH2 and NH3+;
• or
• wherein R2 and R3 are independently selected from:
• hydrogen, cyclohexyl, branched or straight chain C1-C10 alkyl or branched or straight chain C2-C10 alkenyl, wherein the alkyl or alkenyl chains may optionally be interrupted by one or two groups selected from NH and NH2+, and wherein the alkyl, alkenyl or alkynyl chains may optionally be substituted by between one and three substituents selected from the group consisting of:
• phenyl, methoxy, COOH, NH2 and NH3+;
• or
• wherein R2 and R3, together with the nitrogen to which they are attached, form a 4-, 5-, 6- or 7-membered ring which may optionally contain 1, 2, 3, 4 or 5 additional nitrogen atoms and may be saturated, unsaturated or partially unsaturated, and wherein the 4-, 5-, 6- or 7-membered ring may optionally be substituted by one or more substituents selected from the group consisting of:
• SO2NMe2, SO3H, SO2halogen, SO2NH2, —C(O)O(CH2)pPh, —C(O)Me, —C(O)pyridyl, —(CH2)pOH, —C(O)NH2, —COOH, —C(O)NMe2, —C(O)NEt2, phenyl, naphthyl, pyridinyl, pyrimidinyl, pyrazinyl, triazinyl, pyrrolidinyl, imidazolyl, C1-C6-alkyl, C2-C6alkenyl, C2-C6alkynyl, —C(O)OC1-C6alkyl, —C(O)OC2-C6alkenyl, —C(O)OC2-C6alkynyl, —C(O)O(CH2)pPh, —(CH2)pSH, halogen, SO2PhNHCOC1-C6alkyl, NH2, SH, OC1-C6alkyl, and wherein p is a number between 0 and 2;
• or
• wherein R2 and R3, together with the nitrogen to which they are attached, form a 5-, 6-, or 7-membered ring which may optionally contain 1, 2 or 3 additional nitrogen atoms and may be saturated, unsaturated or partially unsaturated, and wherein the 5-, 6-, or 7-membered ring may optionally be substituted by between one and four substituents selected from the group consisting of:
• SO2NMe2, SO2NH2, —COO(CH2)pPh —C(O)Me, —C(O)pyridyl, —(CH2)pOH, —C(O)NH2, —COOH, —C(O)NMe2, —C(O)NEt2, phenyl, pyridinyl, pyrimidinyl, pyrazinyl, triazinyl, pyrrolidinyl, imidazolyl, C1-C6-alkyl, C2-C6alkenyl, C2-C6alkynyl, —C(O)OC1-C6alkyl, —C(O)OC2-C6alkenyl, —C(O)OC2-C6alkynyl, —C(O)O(CH2)pPh, —(CH2)pSH, halogen, NH2, SH, OC1-C6alkyl, p is a number between 0 and 2;
• or
• wherein R2 and R3, together with the nitrogen to which they are attached, form a saturated 5-, 6-, or 7-membered ring which may optionally contain 1, 2 or 3 additional nitrogen atoms, and wherein the 5-, 6-, or 7-membered ring may optionally be substituted by between one and three substituents selected from the group consisting of:
• SO2NMe2, SO2NH2, —C(O)Me, —C(O)pyridyl, —(CH2)pOH, —C(O)NH2, —COOH, —C(O)NMe2, —C(O)NEt2, phenyl, pyridinyl, pyrimidinyl, pyrazinyl, triazinyl, pyrrolidinyl, imidazolyl, C1-C6-alkyl, C2-C6alkenyl, —C(O)OC1-C6alkyl, —C(O)OC2-C6alkenyl, halogen, NH2, SH, OC1-C6alkyl, p is a number between 0 and 2;
• or
• wherein R2 and R3, together with the nitrogen to which they are attached form a structure selected from the group consisting of:
• or
• wherein R2 and R3 are independently selected from C1-C10 alkyl, or alternatively R2 and R3, together with the nitrogen to which they are attached, form a 5- or 6-membered ring which may optionally contain between 1 and 3 additional nitrogen atoms, and which may optionally be substituted with an aryl or heteroaryl group
• and X is selected from the group consisting of:
• wherein R1 is a substituent that corresponds to a substituent attached to the 7-NHC(O)— group of a cephalosporin antibiotic;
• or wherein R1 is Y-aryl or Y-heteroaryl where Y is a bivalent hydrocarbon having between 1 and 4 carbon atoms.