Oxazolidinone And/Or Isoxazoline As Antibacterial Agents

A compound of the formula (I), or a pharmaceutically-acceptable salt, or an in-vivo-hydrolysable ester thereof,

• wherein in (I) C is a biaryl moiety C′—C″
• where C′ and C″ are independently aryl or heteroaryl rings such that the central fragment C is represented by any one of the groups D to L below:
• wherein the groups D to L may be attached to rings A and B in either orientation;
• wherein A and B are independently selected from
• wherein i) and/or ii) are linked as shown in (I) via the 3-position to group C and substituted in the 5-position as shown in (I) by —CH2—R1a and —CH2—R1b;
• R1a, R2b, R1a and Rab are independently hydrogen or fluorine;
• R1a and R1b are independently selected from hydroxy, —OSi(tri-(1-6C)alkyl) (wherein the 3 (1-6C)alkyl groups are independently selected from all possible (1-6C)alkyl groups), —NHC(═W)R4, —OC(═O)R4,
• wherein W is O or S;
• R4 is hydrogen, amino, (1-8C)alkyl, —NHR12, —N(R12)(R13), —OR12 or —SR12, (2-4C)alkenyl, (1-8C)alkylaryl, mono-, di-, tri- and per-halo(1-8C)alkyl, —(CH2)p(3-6C)cycloalkyl or —(CH2)p(3-6C)cycloalkenyl wherein p is 0, 1 or 2;
• wherein in a) HET-1 is a C-linked 5-membered heteroaryl ring containing 2 to 4 heteroatoms independently selected from N, O and S, which ring is optionally substituted on an available carbon atom by 1 or 2 substituents independently selected from (1-4C)alkyl, (2-4C)alkenyl, (3-6C)cycloalkyl, amino, (1-4C)alkylamino, di-(1-4C)alkylamino, (1-4C)alkylthio, (1-4C)alkoxy, (1-4C)alkoxycarbonyl, halogen and cyano and/or on an available nitrogen atom (provided that the ring is not thereby quaternised) by (1-4C)alkyl;
• or
• HET-1 is a C-linked 6-membered heteroaryl ring containing 2 or 3 nitrogen heteroatoms, which ring is optionally substituted on any available C atom by 1, 2 or 3 substituents independently selected from (1-4C)alkyl, (2-4C)alkenyl, (3-6C)cycloalkyl, amino, (1-4C)alkylamino, di-(1-4C)alkylamino, (1-4C)alkylthio, (1-4C)alkoxy, (1-4C)alkoxycarbonyl, halogen and cyano and/or on an available nitrogen atom (provided that the ring is not thereby quaternised) by (1-4C)alkyl;
• wherein in b)
• HET-2 is an N-linked 5-membered, fully or partially unsaturated heterocyclic ring, containing either (i) 1 to 3 further nitrogen heteroatoms or (ii) a further heteroatom selected from O and S together with an optional further nitrogen heteroatom;
• which ring is optionally substituted on a C atom by an oxo or thioxo group;
• and/or which ring is optionally substituted on any available C atom by 1, 2 or 3 substituents independently selected from (1-4C)alkyl, (2-4C)alkenyl, (3-6C)cycloalkyl, amino, (1-4C)alkylamino, di-(1-4C)alkylamino, (1-4C)alkylthio, (1-4C)alkoxy, (1-4C)alkoxycarbonyl, halogen and cyano and/or on an available nitrogen atom (provided that the ring is not thereby quaternised) by (1-4C)alkyl;
• or HET-2 is an N-linked 6-membered di-hydro-heteroaryl ring containing up to three nitrogen heteroatoms in total (including the linking heteroatom), which ring is substituted on a suitable C atom by oxo or thioxo and/or which ring is optionally substituted on any available C atom by 1, 2 or 3 substituents independently selected from (1-4C)alkyl, (2-4C)alkenyl, (3-6C)cycloalkyl, amino, (1-4C)alkylamino, di-(1-4C)alkylamino, (1-4C)alkylthio, (1-4C)alkoxy, (1-4C)alkoxycarbonyl, halogen and cyano and/or on an available nitrogen atom (provided that the ring is not thereby quaternised) by (1-4C)alkyl;
• and wherein at each occurrence, alkyl, alkenyl, cycloalkyl cycloalkenyl in substituents on HET-1 and HET-2, or in R4 is optionally substituted with one, two, three or more F, Cl or CN;
• wherein in c)
• R5 is hydrogen, (3-6C)cycloalkyl, phenyloxycarbonyl, tert-butoxycarbonyl, fluorenyloxycarbonyl, benzyloxycarbonyl, (1-6C)alkyl (optionally substituted by cyano or (1-4C)alkoxycarbonyl), —CO2R8, —C(═O)R8, —C(═O)SR8, —C(═S)R8, P(O)(OR9)(OR10) and —SO2R11, wherein R8, R9, R10 and R11 are as defined hereinbelow;
• R6 is cyano, —COR12, —SO2NHR12, —CONHR12, —CON(R12)(R13), —SO2R12, —SO2NBR12, —SO2N(R12)(R13) or NO2, wherein R12 and R13 are as defined hereinbelow;
• R7 is hydrogen, amino, (1-8C)alkyl, —NHR12, —N(R12)(R13), —OR12 or —SR12, (2-4C)alkenyl, (1-8C)alkylaryl, mono-, di-, tri- and per-halo(1-8C)alkyl, —(CH2)p(3-6C)cycloalkyl or —(CH2)p(3-6C)cycloalkenyl wherein p is 0, 1 or 2;
• R8 is hydrogen, (3-6C)cycloalkyl, phenyl, benzyl, (1-5C)alkanoyl, (1-6C)alkyl (optionally substituted by substituents independently selected from (1-5C)alkoxycarbonyl, hydroxy, cyano, up to 3 halogen atoms and —NR14R15 (wherein R14 and R15 are independently selected from hydrogen, phenyl (optionally substituted with one or more substituents selected from halogen, (1-4C)alkyl and (1-4C)alkyl substituted with one, two, three or more halogen atoms) and (1-4C)alkyl (optionally substituted with one, two, three or more halogen atoms), or for any N(R14)(R15) group, R14 and R15 may additionally be taken together with the nitrogen atom to which they are attached to form an unsubstituted or substituted pyrrolidinyl, piperidinyl or morpholinyl group);
• R9 and R10 are independently selected from hydrogen and (1-4C)alkyl;
• R11 is (1-4C)alkyl or phenyl;
• R12 and R13 are independently selected from hydrogen, phenyl (optionally substituted with one or more substituents selected from halogen, (1-4C)alkyl and (1-4C)alkyl substituted with one, two, three or more halogen atoms) and (1-4C)alkyl (optionally substituted with one, two, three or more halogen atoms), or for any N(R12)(R13) group, R12 and R13 may additionally be taken together with the nitrogen atom to which they are attached to form an unsubstituted or substituted pyrrolidinyl, piperidinyl or morpholinyl group;
• provided that, when group C is group I or group J and both groups A and B are oxazolidinones and the oxazolidinone (A or B) that is linked to the pyridyl group in C bears a substitutent (R1a-CH2 or R1b—CH2 respectively) that is either an hydroxymethyl group or an acetoxymethyl group then the oxazolidinone (B or A) linked to the phenyl group in C is not substituted by an acetamidomethyl group (R1b-CH2 or R1a-CH2 respectively).