MXPA00011593A - Oxazolidinone derivatives, process for their preparation and pharmaceutical compositions containing them - Google Patents

Abstract

Compounds of formula (I), or a pharmaceutically-acceptable salt, or an in-vivo-hydrolysable ester thereof, wherein, for example, X is -O- or -S-;HET is an optionally substituted C-linked 6-membered heteroaryl ring containing 1 or 2 N atoms;Q is selected from, for example, (Q1) and (Q2);R2 and R3 are independently hydrogen or fluoro;T is selected from a range of groups, for example, an N-linked (fully unsaturated) 5-membered heteroaryl ring system or a 3,6-dihydro-(2H)-pyran-4-yl group or a 4-substituted piperazino group;are useful as antibacterial agents;and processes for their manufacture and pharmaceutical compositions containing them are described.

Description

DERIVATIVES OF OXAZOLID NONA, PROCESS FOR ITS PREPARATION AND PHARMACEUTICAL COMPOSITIONS THAT CONTAIN THEM DESCRIPTION OF THE INVENTION The present invention relates to antibiotic compounds and in particular to antibiotic compounds containing a substituted oxazolidinone ring. This invention also relates to processes for their preparation, to intermediates useful in their preparation, to their use as therapeutic agents and to pharmaceutical compositions containing them. The international microbiological community continues to express serious concern to that of the evolution of antibiotic resistance that should result in strains against which the currently available antibacterial agents will be effective. In general, bacterial pathogens can be classified as either Gram positive or Gram negative pathogens. Antibiotic compounds with effective activity against Gram positive and Gram negative pathogens are generally estimated having a broad spectrum of activity. The compounds of the present invention are estimated primarily as effective against Gram positive pathogens because of their particular good activity against pathogens. Gram-positive pathogens, for example Staphylococci, Enterococci, Streptococci and mycobacteria, are particularly important due to the development of resistant strains that are difficult to treat and difficult to eradicate from development in a hospital once established. Examples of such strains are methicillin-resistant staphylococci (MRSA), methicillin-resistant coagulase-negative staphylococci (MRCNS), penicillin-resistant streptococcal pneumonia and multiple-resistant faecium enterococci. Most clinically effective antibiotics for the treatment of Gram-resistant positive pathogens are vancomycin. Vancomycin is a glycopeptide and is associated with nephrotoxicity and ototoxicity. In addition, and more importantly, the antibacterial resistance to vancomycin and other glycopeptides is also apparent. This resistance increases in a continuous speed, making these less and less effective agents in the treatment of Gram positive pathogens. Certain antibacterial compounds contain an oxazolidinone ring that has been described in the art (e.g., Walter A. Gregory et al in J. Med. Chem. 1990, 33, 2569-2578 and Chung-Ho Park et al in J. Med. Chem. 1992, 35, 1156-1165). Such antibacterial oxazolidinone compounds with a 5-methylacetamide side chain can be subjected to mammalian peptidase metabolism. In addition, bacterial resistance knows antibacterial agents that can be developed, for example, by (i) the evolution of the active binding sites in the bacterium that deliver a previously active less effective or redundant pharmacophore, and / or (ii) the evolution of means to chemically deactivate a given pharmacophore. Therefore, there remains a continuing need to find new antibacterial agents with a favorable pharmacological profile, in particular for compounds containing novel pharmacophores. A class of antibiotic compounds containing a new class of substituted oxazolidinone ring that has used activity against Gram positive pathogens including MRSA and MRCNS and, in particular, against several strains showing resistance to vancomycin and against E. faecium strains has been discovered. resistant to aminoglycosides and clinically ß-lactams used. Accordingly, the present invention provides a compound of the formula (I), or a pharmaceutically acceptable salt, or an in vivo hydrolysable ester thereof, where X is -0- or -S-; HET is a 6-membered C-linked heteraryl ring containing 1 or 2 N, whose ring is optionally substituted at any available C atom (with the proviso that when the N atom is adjacent to the X bond, there is no substitution at any of the C atoms which are adjacent to this atom N) by substituents 1, 2 or 3 independently selected from C? _, amino, C? -4 alqu alkylamino, C? _4 alkyl, C? _ alkoxycarbonyl and halogen; Q is selected from Ql to Q9: Ql Q2 Q3 Q4 Q5 Q6 Q7 QS Q9 wherein R2 and R3 are independently hydrogen or fluoro; where Ai is carbon or nitrogen; Bi is 0 or S (or, in Q9 only, NH); Xq is 0, S or N-R1 (wherein R1 is hydrogen, C4_4alkyl or hydroxy-C4_4alkyl); and where in Q7 each A is independently selected from carbon or nitrogen, with a maximum of 2 nitrogen heteroatoms in the 6-membered ring, and Q7 is linked to T by any of the atoms Ai (where Ai is carbon ), and it is bonded in the 5-membered ring by means of the specified carbon atom, or by means of Ai when Ai is carbon; Q8 binds to T via either the carbon atoms specified in the 5-membered ring and bonded to the benzo ring by means of either the two specified carbon atoms on either side of the bond bonds shown; and Q9 is linked by means of either of the two specific carbon atoms on either side of the bond bond shown; wherein T is selected from the groups in (TA) to (ID) below (wherein AR1, AR2, AR2a, AR2b, AR3, AR3a, AR3b, AR4, AR4a, CY1 and CY2 are defined in the following); (TA) T is selected from the following groups: (TAa) AR1, AR1 alkyl of C? _4, AR2 (bound carbon), AR3; (TAb) AR1-CH (OH), AR2-CH (0H), AR3-CH (0H) -; (TAc) Arl-CO, AR2-C0, AR3-C0, AR4-C0; (TAd) AR1-0-, AR2-0-, AR3-0 ,; (TAe) ARl S (0) q-, AR2-S (O) q-, AR3-S (O) q- (q is 0, 1 or 2); (TAf) an optionally substituted (fully unsaturated) N-linked 5-membered heteroaryl ring system containing 1, 2 or 3 nitrogen atoms; (TAg) a bound tropol-3-one or carbon-bound tropol-4-one, optionally substituted at a position not adjacent to the bonding position; or (TB) T is selected from the following groups: - (TBa) halo or C? -4 alkyl. { optionally substituted by one or more groups each independently selected from hydroxy, C? _4 alkoxy, C? -4 alkanoyl, cyano, halo, trifluoromethyl, C 1-4 alkoxycarbonyl, NRvRw, C? _6 alkanoylamino, C_ alkoxycarbonylamino ? 4, N-C 1-4-N-C 1-6 alkanoylamino, C? _ 4 S alkyl (0) q- (q is 0, 1 or 2), CY1, CY2 or AR1}; (TBb) -NRv ^ 1; (TBc) ethenyl, 2-C2-4 alkyletenyl, 2-cyanoethenyl, 2-cyano-2- (C4 alkyl) ethenyl, 2-nitro tentenyl, 2-nitro-2- (C1-4 alkyl,) ethenyl, 2- (C 1 _4) alkylaminocarbonyl ethenyl, 2- ((1-C 1-4 alkoxycarbonyl) ethenyl, 2- (AR 1) ethenyl, 2- (AR 2) ethenyl; (TBd) R 10 CO-, R 10 S (0) - (q is 0, 1 or 2) or R10CS- where R10 is selected from the following groups: { TBda) CY1 or CY2; (EB b) hydrogen, C? _4 alkoxycarbonyl, trifluoromethyl, -NRvRw, ethenyl, 2- (C? _4 alkyletenyl, 2-cyanoethenyl, 2-cyano-2- (C? _4 alkyl) ethenyl, 2-nitrohetenyl , 2-nitro-2- (C? _4) alkyl ethenyl, 2- (C? _4) ethenyl alkylamino, 2- (C? _4) alkoxy ethenyl, 2- (Al) ethenyl or 2- (AR2 ) ethenyl, or (TBdc) C 1-4 alkyl,. {optionally substituted as defined in (TBa) above, or by C 1 4 4 alkyl (0) pNH- or C 1-4 alkyl (O) p - (C 4 alkyl) N- (p is 1 or 2), wherein R v is hydrogen or C 1 -4 alkyl, R w is hydrogen or C 4 alkyl, R v 1 is hydrogen, C? -4 or C3_? Cycloalkyl; Rw1 is hydrogen, C1-4alkyl, C3-scycloalkyl, C1-4alkyl, or alkyl C! _4S (0) q- (q is 1 or 2); or (TC) T is selected from the following groups: - (TCa) a fully saturated, optionally substituted 4-membered monocyclic ring containing a heteroatom selected from 0, N, and S (optionally oxidized), and linked by a nitrogen ring or carbon atom Sp3; (TC) an optionally substituted 5-membered monocyclic ring containing a heteroatom selected from 0, N and S (optionally oxidized), and linked via a nitrogen atom in the ring or a nitrogen atom in the sp3 or sp2 ring , whose monocyclic ring is completely saturated different (where appropriate) to a sp2 bonding carbon atom; . (TCc) an optionally substituted 6 or 7 membered monocyclic ring containing 1 or 2 heteroatoms independently selected from 0, N and S (optionally oxidized), and linked by means of a nitrogen atom in the ring or a nitrogen atom in the sp3 or sp2 ring whose monocyclic ring is completely saturated other than (where appropriate) at a bound sp2 carbon atom; or (TD) T is selected from the following groups: (TDa) a spirobicyclic ring system containing 0, 1 or 2 rings of nitrogen atoms as the only heteroatom rings, the structure consists of a ring system of 5 or 6 members (attached by a ring of a nitrogen atom in the ring or a sp3 or sp2 carbon atom) substituted (but not adjacent to the bonding position) by a bound spiro carbon ring of 3, 4 or 5 members; whose bicyclic ring system is (i) fully saturated other than (where appropriate) at a bond sp2 carbon atom; (ii) contain a group N (RC) - in the ring system (at least two carbon atoms outside the bonding position when the bond is via a nitrogen atom or a sp2 carbon atom) or a group -N (RC) - in an optional substituent (not adjacent to the bonding position) and is (iii) optionally further substituted on a ring of available carbon atom; or (TDb) a 1-, 8- or 9-member bicyclic ring system (attached via a ring nitrogen atom or a Sp3 or sp2 carbon atom ring) containing 0, 1 or 2 ring nitrogen atoms (and optionally an additional 0 or S ring heteroatom), the structure contains a bridge of 1, 2 or 3 carbon atoms; whose bicyclic ring system is (i) fully saturated other than (where appropriate) at a carbon atom sp2 carbon bond; (ii) contains a 0 or S heteroatom, or a group - N (RC) in the ring (at least two carbon atoms outside the bonding position when the bond is via a nitrogen atom or a hydrogen atom) carbon sp) or a group - N (RC) - on an optional substituent (not adjacent to the bonding position) and is (iii) optionally further substituted on an available carbon atom ring; wherein RC is selected from the groups (RC1) to (RC5): (Rcl) alkyl of C? _e. { optionally substituted by one or more C 1-4 alkanoyl groups (including disubstitution geminal disubstitution) and / or optionally monosubstituted by cyano, C 1-4 alkoxy, trifluoromethyl, alkoxycarbonyl of C? 4, phenyl (optionally substituted as AR defined in the following), C? _4S alkyl (0) q- (q is 0, 1 or 2); or, except the first carbon atom of the C? _6 alkyl chain, optionally substituted by one or more groups (including geminal disubstitution) each independently selected from hydroxy and fluoro, and / or optionally monosubstituted by oxo, -NRvRw [in where Rv is hydrogen or C 1-4 alkyl; Rw is hydrogen or C? _4alkyl], C alca-alca alkanoylamino, C? _4alkoxycarbonylamino, C C -4--N-C 1-4 alkanoylamino N-alkyl, C alquilo _S (0) pNH- alkyl or C 1-4 alkyl (0) p- (C 4 alkyl) N- (p is 1 or 2)}; (Rc2) R13CO-, R13S0Z or R13CS- where R13 are selected from (Rc2a) to (Rc2e): (Rhea) AR1, AR2, AR2a, AR2b, AR3, AR3a, AR3b, AR4, AR4a, CY1, CY2; (Rc2b) hydrogen, C1-4 alkoxycarbonyl, trifluoromethyl, -NRvRw [wherein Rv is hydrogen or C? -4 alkyl; Rw is hydrogen or C1-4alkyl], ethenyl, 2-alkyletenyl of C4-4, 2-cyanohetenyl, 2-cyano-2- (C1-4alkyl) ethenyl, 2-nitrohetenyl, 2-nitro-2- (C ?4 alkyl) ethenyl, 2- (C1-) alkylamino) ethenyl, 2- (C1-4 alkoxycarbonyl) ethenyl, 2- (AR1) ethenyl, 2- (AR2) ethenyl, 2- (AR2a) ethenyl; (Rc2c) C? _? 0 alkyl. { optionally replaced by one or more groups (including geminal disubstitution) each independently selected from hydroxy, C 1-10 alkoxy, C? - alkoxy C? _4 alkoxy / C? _4 alkoxy C? _4 alkoxy C? _4 alkoxy, alkanoyl C? _4 and amino; and / or optionally substituted by a selected phosphonate group [phosphono, -P (0) (OH) 2, and mono- and di-alkoxy derivatives of C? _4 thereof, phosphinate [-P (OH) 2 and derivatives mono- and di-C 1-4 alkoxy thereof], phosphoryl [-0-P (OXOH) 2, and mono- and di-alkoxy derivatives of C 1-4 thereof], phosphoryl [-0-P (OH 2 and monomers and di-C 1-4 alkyl thereof], cyano, halo, trifluoromethyl, C 1-4 alkoxycarbonyl, C 1-4 alkoxy C 1-4 alkoxycarbonyl, C 1-4 alkoxy-alkoxy C 1-4-C 1-4 alkoxycarbonyl, C 1-4 alkylamino, di (C? 4 alkyl) amino, C 1-6 alkanoylamino, C 1-4 alkoxycarbonylamino, C? -4-N- N- alkyl C 1-6 alkanoylamino, C 1-4 alkylaminocarbonyl, di (C 1-4 alkyl) aminocarbonyl, C 1-4S alkyl (0) pNH-, C 1-4 alkyl (0) p- (C? _4) N-, fluoroalkyl of C 1-4S (0) pNH-, fluoroalkyl of C? _4S (O) p- (alkyl of d-YN-, alkyl of C? _4S (0) q-, CYl, CY2, ARl, AR2, AR3, ARl-0, AR2-0, AR3-0, ARl-S (O) q-, AR2-S (0) q-, AR3-S (0) q-, AR1- NH-, AR2-NH-, AR3-NH- (p is 1 or 2 and q is 0, 1 or 2), and also AR2a, AR2b, AR3a and AR3b versions of groups containing AR2 and AR3}; (Rc2d) R14C (0) Oalkyl of C? _6 wherein R14 is AR1, AR2, C? -4 alkylamino, benzyloxyC1-4alkyl or C? -? Rj alkyl. { optionally substituted as defined by (Rc2c)}; (Rc2e) R150- wherein R15 is benzyl, C4 _4 alkyl. { optionally substituted as defined by (Rc2c)} , CY1, CY2 or AR2b; (Rc3) hydrogen, cyano, 2-cyanoethenyl, 2-cyano-2- (C4-4 alkyl) ethenyl, 2- (C4-4 alkylaminocarbonyl) ethenyl, 2- (C1-4 alkoxycarbonyl) ethenyl, -nitroetenyl, 2-nitro-2- (C 1-4 alkyl) ethenyl, 2- (AR 1) ethenyl, 2- (AR 2) ethenyl, or of the formula (Rc 3a) (Rc3a) wherein X00 is -OR17, -SR17, -NHR 17 N (R17) 2; wherein R. 17 is hydrogen (When X 00 is -NHR, 17 N (R> 1X7 ') 2), and R 17 is C 1 alkyl, phenyl or AR 2 (When Xo 0 is -OR 17, -SR 17 and - NHR17); and R16 is cyano, nitro, C alqu _ alkylsulfonyl, C4_ cycloalkylsulfonyl, phenylsulfonyl, C? _4 alkanoyl and C? _4 alkoxycarbonyl; (Rc4) trifly, AR1, AR2, AR2a, AR2b, AR3, AR3a, AR3b; (Rc5) RdOC (Re) = CH (C = 0) -, RfC (= 0) C (= 0) -, RgN = C (Rh) C (= 0) - or RiNHC (Rj) = CHC (= 0) - where Rd is C? _6 alkyl; Re is hydrogen or C? -6 alkyl, or Rd and Re together form an alkylene chain of C3_4; Rf is hydrogen, C? _6 alkyl, C? _6 hydroxyalkyl, C? -46alkyl alkoxy, NRvRw [wherein Rv is hydrogen or C? _4 alkyl; Rw is hydrogen or C? _4] alkyl, C? _6 alkoxy, C? _6 C? _? Alkoxy alkoxy, C2_6 hydroxyalkoxy, C2_6 Ci_4alkoxy alkylamino, C2_6 C? -4alkoxy dialkylamino.; Rg is C? _6 alkyl, hydroxy or C? -β alkoxy; Rh is hydrogen or C? -6 alkyl, * Ri is hydrogen, C? _6 alkyl, AR1, AR2, AR2a, AR2b and Rj is hydrogen or C? _6 alkyl; wherein AR 1 is an optionally substituted phenyl or optionally substituted naphthyl; AR2 is an optionally substituted 5 or 6 membered monocyclic heteroaryl ring, completely unsaturated (i.e. with the maximum degree of unsaturation) containing up to four heteoatoms independently selected from 0, N and S (but not containing any of the 0 bonds). -0, OS or SS), and linked by means of a ring of carbon atom or a ring of carbon atom if the ring is therefore not quaternized; AR2a are a partially hydrogenated version of AR2 (ie AR2 systems that retain some, but not completely the degree of unsaturation), linked by means of a ring of carbon atom or linked by means of a nitrogen atom in the ring if the ring is therefore not quaternized; AR2b is a fully hydrogenated version of AR2 (ie AR2 systems that do not have unsaturation), linked by means of a ring of carbon atom or linked by means of a nitrogen atom in the ring; AR3 is an optionally substituted 8, 9 or 10 membered bicyclic heteroaryl ring, completely unsaturated (i.e. with the maximum degree of unsaturation) bicyclic heteroaryl ring containing up to four heteroatoms independently selected from 0, N and S (but not containing any of the OO, OS or SS bonds), and linked by means of a ring of carbon atom in any of the rings comprising the bicyclic system; AR3a is a partially hydrogenated version of AR3 (ie AR3 systems that retain some, but not the filling, degree of unsaturation), linked by means of a ring of carbon atom, or linked by means of a nitrogen atom in the ring if the ring is not therefore quaternized, in any of the rings that comprise the bicyclic system, AR3b is a completely hydrogenated version of AR3 (ie AR3 systems that do not have unsaturation), bound by means of a carbon atom, or linked via a nitrogen atom in the ring, in any of the rings, comprising the bicyclic system; AR4 is an optionally unsubstituted 13- or 14-membered tricyclic heteroaryl ring (i.e. with the maximum degree of unsaturation) containing up to four heteroatoms independently selected from 0, N, and S (but does not contain any of the 0-bonds) 0, 0-S or SS), and joined by means of a ring of carbon atom in any of the rings comprising the tricyclic system; AR4a is a partially hydrogenated version of AR4 (ie AR4 systems containing some, but not all, of the degree of unsaturation), linked by means of a ring of carbon atom, or linked by means of a nitrogen atom in the ring if the ring is not therefore quaternized, if any of the rings comprises the tricyclic system; CY1 is an optionally substituted cyclobutyl, cyclopentyl or cyclohexyl ring, CY2 is an optionally substituted cyclopentyl or cyclohexyl ring.

In this specification, wherein it is stated that the ring can be linked by means of a sp2 carbon atom whose ring is completely saturated other than (where appropriate) at a sp2-linked carbon atom: it is understood that the ring is linked by means of a double bond C = C. In another embodiment, (Rcl) is as previously defined different from the optional phenyl substituent on C? _e alkyl, they are optionally substituted as ARl defined in the following; and (Rc2c), is as defined in the foregoing and further includes carboxy as an optional substituent on R13 as C? _? o alkyl. (TAf) Where T is an optionally substituted N-linked (fully unsaturated) 5-membered heteroaryl ring system containing 1, 2 or 3 nitrogen atoms, is preferably selected from a group of formula (TAf1) a (TAf6) below (particularly (TAfl), (TAf2),. { TAf4) and (TAf5), and especially (TAfl) and / or (TAf2)). The above preferred values of (TAf) are particularly preferred when presented in Q1 or Q2, especially Q1, and When X is -0-.

(TAf4) (TAl5) (TAf6) wherein: R6 is selected (independently where appropriate) from hydrogen, C1-4 alkyl, C1-4 alkoxycarbonyl, C4-4 alkanoyl, carbamoyl and cyano; R4 and R5 are independently selected from hydrogen, halo, trifluoromethyl, cyano, nitro, C4 alkoxy, C1-4S alkyl (0) q- (q is 0, 1 or 2), C1-4 alkanoyl, C1 alkoxycarbonyl -4, C2-4 alkanoyloxy-C1-4 alkyl, benzoxy-C4-4 alkyl, C2-4 alkanoylamino, -CONRvRw, NRvRw and C1-4 alkyl. { optionally substituted by hydroxy, trifluoromethyl, cyano, nitro, C? _4 alkyl, C? _ S alkyl (0) q- (q is 0, 1 or 2), C 1-4 alkoxycarbonyl, C? _4 alkanoylamino, -CONRvRw, -NRvRw; wherein R v R w is hydrogen or C 4 alkyl; Rw is hydrogen or C? _ Alkyl}; or R4 is selected from one of the groups in (TAfa) a (TAfC) below, or (where appropriate) one of R4 and R5 is selected from the above list of values R4 and R5, and the other is selected from one of the groups in (TAfa) to (TAfc) below: (TAfa ) a group of the formula (TAfal) (TAfal) wherein Z ° is hydrogen or C? _4 alkyl; Xo and Y ° are independently selected from hydrogen, C? _4 alkyl, C? _4 alkoxycarbonyl, halo, cyano, nitro, C? _S alkyl (0) q- (q is 0, 1 or 2), RvRwNS02- trifluoromethyl, pentafluoroethyl, C? _4 alkanoyl and CONRvRw [wherein Rv is hydrogen or C? -4 alkyl; Rw is hydrogen or C1-4 alkyl]; or one of Xo and Y ° is selected from the above list of values Xo and Y °, and the others are selected from phenyl, phenylcarbonyl, -S (0) q-phenyl (q is 0, or 2) N- ( phenyl) carbamoyl, phenylaminosulfonyl, AR2, (AR2) -C0, (AR2) -S (0) q- (q is 0, 1 or 2), N- (AR2) carbamoyl and (AR2) aminosulfonyl; wherein any phenyl group in (TAfa) can be optionally substituted by up to three substituents independently selected from C ?4 alkyl, cyano, trifluoromethyl, nitro, halo and alkylsulfonyl of C? -; (TAfb) an acetylene of the formula - = - H or - = - alkyl of C? _4; . { TAfc -X1-Y1-AR2, -X1-Y1-AR2a, -X1-Y1-AR2b, -X ^ Y1-AR3, -X1-Y1-AR3a or -X1-Y1-AR3b; 'wherein X1 is a direct bond or -CH (OH) - and is - (CH2): - (CH2) n-NH- (CH2) m, -CO- (CH2) m-C0NH- (CH2) m- -C (= S) NH- (CH2) m- or -C (= 0) 0- (CH2) m-; or wherein X1 is -CH20-, -CH2NH- or -CH2N (C? 4) - and Y1 is -CO- (CH2) m-, -CONH- (CH2) m- or -C (= S) NH- (CH2) m-; and further Y1 is -S02- when X1 is -CH2NH- or CH2N (C1-4 alkyl) - wherein n is 1, 2 or 3; m is 0, 1, 2 or 3 and q is 0.1 or 2; and when Y1 is - (CH2) m_NH- (CH2) m_ each m is independently selected from 0, 1, 2 or 3. It is understood that when a value for -X1- is a bond of two atoms and is written, for example , like -CH2NH- is the left part (-CH2-here) which joins the group of the formula (TAfl) to (TAf6) and the right part (-NH-here) which joins -Y1- in the definition (TAfc). Similarly, when -Y1- is a bond of two atoms and is written, for example, as -CONH- it is the left part of -Y1 - (- CO- here) which joins the right part of -X1-, and the right part of -Y1- (-NH-here) which joins the portions AR2, AR2a, AR2b, AR3, AR3a or AR3b in the definition in (TAfc). Preferably R6 is hydrogen or C1-4alkyl, and R4 and R5 are independently selected from hydrogen, C1-4alkyl or one of R4 and R5 is selected from the group (TAfa). Other preferred substituents on (TAfl) to (TAf6) are illustrated in the appended examples. (TAg) When T is tropol-3-one or carbon-bound tropol-4-one, optionally substituted and in the position not adjacent to the linked position (TAg), it is preferably selected from a group of the formulas (TAgl), (TAg2) or (TAg3). Preferred above values of (TAg) are particularly preferred when present in Ql or Q2, especially Ql, and When X is -O-. wherein R is selected from (TAga) hydrogen, C1-4 alkyl. { optionally substituted by one or two substituents (excluding geminal disubstitution) independently selected from fluoro, hydroxy, C1-4 alkoxy and NRvRw]}; or (TAgb) R8-0, R8-S-, R8-NH- or R8R8-N; wherein R is selected (independently where appropriate) from hydrogen, C 1-4 alkyl or C 3-8 cycloalkyl. { both optionally substituted by one or two substituents (excluding geminal disubstitution) independently selected from hydroxy, C4 alkoxy, C4-4 alkoxycarbonyl and NRvRw} , C2-4 alkenyl,. { optionally substituted by one or two NRvRw substituents} , C1-4 alkanoyl. { optionally substituted by one or two substituents independently selected from NRvRw and hydroxy} , phenyl-C 1-4 alkyl or pyridyl-C 1-4 alkyl. { the phenyl and pyridyl (preferably pyridin-4-yl) are optionally substituted by one or two NRvRw substituents}; or (TAgc) morpholino, thiomorpholino, pyrrolidino. { optionally and independently substituted in the 3- and / or 4- positions by C 1-4 alkyl} , piperidino substituted at the 4-position by R9-, R9-0-, R9-S-, R9-NH- or R9R9-N-; wherein R9 is selected (independently where appropriate) from hydrogen, C1-4 alkyl. { optionally substituted by one or two (excluding gem-disubstitution) hydroxy, C1-alkoxy, C1-4 alkoxycarbonyl, or -NRvRw} and piperazine. { optionally substituted in the 4-position with C? _4 alkyl, C3_8 cycloalkyl, C? _4 alkanoyl, C-4 alkoxycarbonyl or C C1-4 alqu alkylsulfonyl, and optionally and independently substituted in the 3- and / or 5-position - by C1-4 alkyl}; wherein Rv is hydrogen or C? _4 alkyl; Rw is hydrogen or C1-4 alkyl. (TC) Preferred values for the optional substituents and the groups defined in (TCa) to (TCc) are defined by the formula (TC1) to (TC4): (TC1) (TC2) (TC3) (TC4) where in (TC1): > A3-B3- es > C (Rq) -CH (Rr) - and G is -O-, -S-, -SO-, -S02- or > N (Rc); where in (TC2): the ml is 0, 1 or 2; > A3-B3- es > C = C (Rr) or > C (Rq) -CH (Rr) - and G is -0-, -S-, -SO-, -S02- or > N (Rc); where in (TC3): ml is 0, 1 or 2; > A3-B3- es > C (Rq) -CH (Rr) (different when Rq and Rr are together hydrogen) and G is -0-, -S-, -SO-, -S02- or > N (Rc); where in (TC4): the ni is 1 or 2; ol is 1 or 2 and ni + ol = 2 or 3; > A3-B3- es > C = C (Rr) or > C (Rq) -CH (Rr) - or > N-CH2- and G is -0-, -S-, -SO-, -S02- or > N (Rc); R p is hydrogen, C 1-4 alkyl (different when such substitution is defined by > A3-B3-), hydroxy, C 1-4 alkoxy or C? _4 alkanoyloxy; where in (TC1), (TC2) and (TC4); ml, ni and ol are as defined in the above: > A3-B3- es > N-CH2- and G is > C (R11) (R12), > C = 0, > C-0H, > C 1-4 -alkoxy, > C = N-OH, > C = C 1-4 -alkoxy, > C = N-NH-C 1-4 alkyl, > C = NN ((C 1 4 alkyl) 2 (the last two C? _4 alkyl groups above in G being optionally substituted by hydroxy) or > C = NN-C0-C alco4 alkoxy, - in where > represents two simple links; Rq is hydrogen, hydroxy, halo, C1-4 alkyl or C ?4 alkanoyloxy, - Rr is (independently where appropriate) hydrogen or C 4 alkyl; R11 is hydrogen, C1-4 alkyl, fluoroalkyl C 1-4, C 1-4 alkylthio-C 1-4 alkyl or hydroxyC 1-4 alkyl and R 12 is - [C (Rr) (Rr) J ^ -N (Rr) (Re) where is 0, 1 or 2; and, different from the substituted ring defined by G, > A3-B3- and Rp, each ring system may optionally also be substituted on a carbon atom adjacent to the bond at > A3- up to two substituents independently selected from C ?4 alkyl, fluoro-C alquilo-4 alkyl (including trifluoromethyl), C? -4-thiol alkyl-alkyl C_4, C 1-4 hydroxy-C 1-4 alkyl, C 1-4 -alkyl / C 1-4 -alkanoylamino, C 1-4 -alkyl-C 1-4 -alkyl, carboxy, C 1-4 -alkoxycarbonyl, AR-oxymethyl , AR-thiomethyl, oxo (= 0) (different when G is> N-Rc and Rc is from group (Rc2) defined in the above) or independently selected from Rc; and also hydroxy or halo (the last two optional substituents only when G is -0- or -S-); where AR is as defined by the following formula (IP); Rc is selected from the groups (Rcl) to (Rc5) defined in the above. To avoid doubt, () m ?, () ni and () oí indicate (-CH2-) m ?, (-CH2-) n? and (-CH2-) 0 ?, respectively (optionally substituted as described in the above).

In the above definition of (TC1) through (TC4) and the additional optional substituents, AR is preferably AR2, and additional optional substituents not selected from the values listed by Rc. A preferred value for G is > N (Rc) or > C (R11) (R12). Particularly preferred values for the optional substituents and the groups defined in (TCa) to (TCc), and (TC1) to (TC4) are continued in the following definitions (TC5) to (TC11): (TC5) (TC6) (TC7) (TC8) (TC9) (TC10) (TC11) where Rc has any of the values listed in the above or in the following. Especially preferred are (TC5), (TC6), (TC7) and (TC9), more specifically (TC5) in which Rc has any of the values listed in the above or in the following (especially R13C0- with the preferable R13 values) given in the following). In (TC5) Rc is preferably selected from the group (Rc2), especially R13C0-with the preferable R13 values given in the following. In (TC7) Rc is preferably selected from the group (Rc3) or (Rc4). The preferred values in the above from (TCa) to (TCc) are particularly preferred when they are present in Q1 or Q2, especially Q1, and when X is -O-. (TDa) When T is a bicyclic spiro ring system as defined in (TDa), it is preferably selected from a group of the formula (TDal) to (TDa9). The preferred values in the above of (TDa) are particularly preferred when they are present in Q1 or Q2, especially Q1, and when X is -0-.

(TDa1) (TDa2) (TDa3) (TDa4) (TDa5) (TDa6) (TDa7) (TDa8) (TDa9) where; (i) the linking group A4 is a nitrogen atom or a sp3 or sp2 carbon atom (with the double bond, where appropriate, oriented in any direction); and (ii) one of the rings of carbon atoms at the positions marked * and ** are replaced by one of the following groups -NRc-, > CH-NHRc, > CH-NRc-C alquilo4 alkyl / > CH-CH2-NHRc, > CH-CH2-NRc-C alquilo4 alkyl [wherein a central -CH2- chain link is optionally mono- or di-substituted by [C ?4 alkyl]; with the proviso that the positions marked with * are not replaced by -NH- in the ring that contains when A4 is a nitrogen atom or a sp2 carbon atom and those positions marked * are not replaced by -NH- in the ring of three members in (TDal), (TDa4) and (TDa5); and (iii) the ring system is optionally (further) substituted on a carbon atom ring available by up to two substituents independently selected from C? -4 alquilo4 alkyl / Coro _4 fluoroalkyl (including trifluoromethyl), C alquilo alquilo alkyl; -4-thio-C 1-4 -alkyl, hydroxy-C 1-4 -alkyl, amino, amino-C 1-4 -alkyl, C 1-4 -alkynoylamino, C 1-4 -alkanoylamino-C 1-4 -alkyl, carboxy, alkoxycarbonyl of C1-4, AR2-oxymethyl, AR2-thiomethyl, oxo (= 0) (different when the ring contains a> N-Rc and Rc is of group (Rc2)) and also hydroxy or halo; where Rc has any of the values listed in the following or in the foregoing. (TDb) When T is a 7, 8 or 9 member bicyclic ring system containing a bridge of 1, 2 or 3 carbon atoms as defined in (TDb), it is preferably selected from a group defined by ring skeletons shown in the formula (TDb 1) to (TDb 14): - 7-member ring skeletons [4,1,0] [3,2,0] [3.1.1] [2,2,1] (TDb1) (TDb2) < TDb3) (TDb4) 8-member ring skeletons [3,3,0] [4,2,0] [4,1,1] [3,2,1] [2,2,2] (TDb5) (TDb6) (TDb7) (TDbd) (TDb9) 9 member ring skeletons [4,3,0] [5,2,0] [4,2,1] [3,3,1] [3,2,2] (TDb10) (TDb11) (TDb12) (TDb13) (TDb14) where; (i) the ring system contains 0, 1 or 2 rings of nitrogen atoms (and optionally an additional 0 or S ring heteroatoms), and when the nitrogen ring is present, the heteroatom / heteroatoms O or S are in any different position as part of the 3 membro ring (TDbl); (ii) the ring system is attached by means of a nitrogen atom in the ring or a ring of sp3 or sp2 carbon atom (with the double bond, where appropriate, oriented in any direction) from any position in the ring any ring [other than a bridge head position or a sp2 carbon atom in the ring of 4. members in (TDb2), (TDbd) and (TDb 11)]; (iii) one of the ring of carbon atoms in a position not adjacent to the bonding position is replaced (different when the ring contains a 0 or S heteroatom) by one of the following groups -NRc- [not in a head position] of bridge], > C (H) -NHRc, > C (H) -NRc-C 1-4 alkyl, > C (H) -CH2-NHRc, > C (H) -CH2-NRc-alkyl of C? _4 [where the hydrogen atom shown in brackets is not present when the replacement is made in a bridgehead position and where a chain link -CH2- is central is optionally mono- or di-substituted by C 1-4 alkyl]; with the proviso that when the ring system is bonded by means of a nitrogen atom in the ring or a sp2 carbon atom any replacement of a ring of carbon atom by -NRc-, 0 or S is at least two carbon atoms outside the bonding position; and (iv) the ring system is optionally (further) substituted on a carbon atom ring available as per the bicyclic spiro ring systems described in (TDa); where Rc has any of the values listed in the above or in the following. It will be appreciated that unstable anti-Bredt compounds are not contemplated in this definition (ie compounds with structures (TDb3), (TDb4), (TDb7), (TDb8), (TDb9), (TDbl2), (TDbl3) and (TDbl4) in which a sp2 carbon atom is directed towards a bridgehead position). Particularly the preferred values of (TDb) are the following structures of the formula (TDb4), (TDb8) and / or (TDb9); where Rc has any of the values listed in the above or in the following. The above preferred values of (TDb) are particularly preferred when they are present in Q1 or Q2, especially Q1, and when X is -0-.

(TDb4a &b) (TDb8) (TDb9) In another embodiment, there is provided a compound of formula (I) which is defined by the formula (IP) or a paceutically acceptable salt or an in vivo hydrolysable ester thereof, in where X is -O- or -S-; HET is a heteroaryl ring of C-linked members containing 1 or 2 N, (with the proviso that pyrimidin-2-yl is executed), whose ring is optionally substituted on any available C atom (provided that when the atom is N is adjacent to the bond X, there is no substitution at any C atom that is adjacent to this atom N) by 1, 2 or 3 independent substituents selected from C 1 -4 alkyl, amino, C 1 -4 alkylamino, C 1 alkoxy -4 and halogen; (IP) wherein: R2 and R3 are independently hydrogen or fluoro; R p is hydrogen, C 4 -hydroxy alkyl, C 4 alkyl or C 2 alkanoyloxy; > A-B is of the formula > C = C (Rr) -, > CHCHRr-, C (OH) CHRr or > N-CH2- (> represents two single bonds) wherein Rr is hydrogen or C? _4 alkyl; D is O-, -S-, -SO-, - S02- or > NRcp; Rpl and Rp2 are independently oxo (= 0) [but not when Rep is of the following group (PC)], C? -4 alkanoylamino of C? -4-C 1 -4 alkyl, hydroxy C alquilo _ alkyl; 4, carboxy, C1-4 alkoxycarbonyl, AR-oxymethyl, AR-thio ethyl (wherein AR is as defined in the following) or independently as defined by RCp in the following with the proviso that Rpl and Rp2 are not phenyl, benzyl, AR (as defined in the following), a tetrazole, cyclopentyl or cyclohexyl ring system; and when D is O or S, Rpl and Rp2 are additionally independently hydroxy or bromine; wherein Rep is selected from (PA) to (PE) as follows: (PA) is hydrogen, cyano, 2- (C 1-4 alkoxycarbonyl) ethenyl, 2-cyanoethenyl, 2-cyano-2- (C 1 -C 6 alkyl) ? 4) ethenyl, 2- (C? _4) alkylaminocarbonyl ethenyl; (PB) phenyl, benzyl, AR (as defined in the following) or a tetrazole ring system [optionally mono-substituted at the 1 or 2 position of the tetrazole ring by C1-4 alkyl, C2-4 alkenyl, alkynyl of C2-4 or C1-4 alkanoyl] wherein the tetrazole ring system binds to nitrogen in > NRCp for a ring of carbon atom; (PC) R13pCO, R13pS02- or R13pCS wherein R13p are selected from (PCa) a (PCf): (PCa) AR (as defined in the following); (PCb) cyclopentyl or cyclohexyl, 1,3-dioxolan-4-yl, 1,3-dioxonlan-4-yl or 1,4-dioxan-2-yl [optionally mono- or di-substituted independently by substituents independently selected from C1-4 alkyl (including geminal disubstitution), hydroxy (but excluding 1,3-dioxolan, -4-yl, 1,3-dioxan-4-yl or 1,4-dioxan-2-yl substituted by hydroxy), C.sub.4 alkoxy, C.sub.1-4 alkylthio acetamido, alkanoyl, cyano and trifluoromethyl]; (PCc) hydrogen, C 1-4 alkoxycarbonyl, trifluoromethyl, amino, C 1-4 alkylamino, di (C 1-4 alkyl) amino, 2- (5- or 6- membered heteroaryl) ethenyl, 2- (de 5) or 6- (partially) hydrogenated heteroaryl) ethenyl, 2-phenylethenyl [wherein the heteroaryl or substituted phenyl is optionally substituted at one available carbon atom up to three substituents independently selected from C 1-4 alkoxy, halo, cyano and (for the substituted phenyl only) C 1-4 alkylsulfonyl]; (PCd) C 1-10 alkyl [optionally substituted by one or more groups (including geminal distribution) each independently selected from hydroxy and amino, or optionally monosubstituted by cyano, halo, C? _ alco alkoxy, trifluoromethyl, C? -4-alkoxy of C? _4alkoxy, C? _4alkoxy-C de _4alkoxy-C 1 -4 -alkoxy, C? _ alcaalkanoyl, alkoxycarbonyl of C 1-4, C 1-4 alkylamino, di (C 1-4 alkyl) amino, C? -6 alkanoylamino, C 1-4 alkoxycarbonylamino, N? C 1-4 -N-C 2-6 alkanoylamino, alkyl of C 1-4S (O) pNH-, C 1-4 alkyl (O) p- (C 1-4 alkyl) N-, fluoroalkyl of C? _4S (O) pNH-, fluoro C? _ 4S alkyl (0) ) p (C 4 _4) N- alkyl, phosphono, C 1 _ (hydroxy) phosphoryl alkoxy, C 1-4 alkoxyphosphoryl, C 4 _ 4 S (0) q-, phenyl, naphthyl, phenoxy, naphthhoxy , phenylamino, naphthylamino, phenylS (O) q-, naphthylS (O) q- [wherein such phenyl and naphthyl groups are optionally substituted by up to three substituents independently selected from C? _4 alkoxy, halo and cyano], or CY ( as defined in the following), where p is 1 or 2 and q is 0, 1 or 2]; (PCe) R14pC (O) O-alkyl of C? -6 wherein R14p is an optionally substituted by 5 or 6 heteroaryl members, optionally substituted phenyl, C? _4 alkylamino, C? _4 benzyloxyalkyl or C? _? optionally substituted; (PCf) R15p0- wherein R15p is benzyl or optionally substituted (1 6C) alkyl; (PD) RdOC (Re) = CH (C = 0), RfC (= 0) C (= 0) -, RgN = C (Rh) C (= 0) or RiNHC (Rj) = CHC (== 0) -, where Rd is C? _6 alkyl; Re is hydrogen or alkyl of C? _g or Rd and Re together form an alkylene chain of C3-4; Rf is hydrogen, C6_6alkyl, hydroxyC1-6alkyl, C6_6alkoxy-C6_6alkyl, amino, C4_4alkylamino, C4_4alkylamino, C4alkoxy ? 6, C? -6-alkoxy of C? _6 alkoxy, hydroxy-C2_6-alkoxy, C2-6 C? _4_ alkoxy alkyloxy, C2_6 alkylamino of C2_? Alkylamino; Rg is C? _6 alkyl, hydroxy or Cx-e alkoxy; Rh is hydrogen or C? _6 alkyl, "Ri is hydrogen, optionally substituted phenyl Ci-e alkyl or an optionally substituted 5- or 6-membered heteroarylolo [and (partially) hydrogenated versions thereof and Rj is hydrogen or Ci-e alkyl (PE) R16pCH (R17p) (CH2) mp_ where mp is 0 or 1; R17p are fluorine, cyano, C1-4 alkoxy, C1-4 alkylsulfonyl, C4-4 alkoxycarbonyl or hydroxy , (with the proviso that when the mp is 0, R, 17P is not fluorine or hydroxy) and R16P is hydrogen or C1-4alkyl, wherein AR is optionally substituted phenyl, C1-4 phenylalkyl, optionally substituted naphthyl 5 or 6 membered heteroaryl optionally substituted, wherein AR is also an optionally substituted 5/6 or 6/6 bicyclic heteroaryl ring system, in which the bicyclic heteroaryl ring system may be attached via an any of the rings comprising the bicyclic system, and wherein the mono-ring systems and bicyclic heteroaryl are linked by means of a ring of carbon atom and can be partially (hydrogenated); wherein Cy is selected from: (i) cyclobutyl, cyclopentyl, cyclohexyl, cyclopentyl or cyclohexenyl ring; (ii) 5- or 6-membered heteroaryl, 5 or 6-heteroaryloxy, 5- (6-membered) heteroaryl, 5- or 6-membered heteroarylane (and (partially) hydrogenated versions thereof) and ( iii) bicyclic heteroaryl of 5/6 or 6/6, bicyclic heteroaryloxy of 5/6 or 6/6, bicyclic heteroaryl of 5/6 or 6/6 S (0) q-, bicyclic heteroarylamino of 5/6 or 6/6 [and (partially) hydrogenated versions thereof]; in aforementioned in CY can be optionally substituted up to three substituents independently selected from halo, C1- alkyl [including geminal disubstitution when CY is a cycloalkyl or cycloalkenyl ring in (i)], acyl, oxo and nitro-C1- alkyl Four. For evasion of doubt, the phosphono is -P (0) (0H) 2; C 4 -hydroxy phosphoryl alkoxy is a C 1 -alkoxy -derivative of -0-P (0) (OH) 2; and di-alkoxyphosphoryl of C? _4 is a di-alkoxy derivative of C? _4 of -0-P (O) (0H) 2. In this embodiment of the formula (IP) a "5- or 6- membered heteroaryl" and "heteroaryl ring (monocyclic)" means a 5- or 6- membered aryl ring wherein (unless otherwise stated) way) 1, 2 or 3 ring atoms are selected from nitrogen, oxygen and sulfur. Unless stated otherwise, such rings are completely aromatic. Particular examples of 5- or 6- membered heteroaryl ring systems are furan, pyrrole, pyrazole, imidazole, triazole, pyrimidine, pyridazine, pyridine, isoxazole, oxazole, isothiazole, thiazole and thiophene. In this embodiment of the formula (IP) a '5/6 or 6/6 bicyclic heteroaryl ring system and' heteroaryl ring (bicyclic) 'means an aromatic bicyclic ring system comprising a 6-membered ring fused to Whether it is a 5-membered ring or another 6-membered ring, the bicyclic ring system contains 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur. Unless otherwise stated, such rings are completely aromatic. Particular examples of the 5/6 and 6/6 bicyclic ring systems are indole, benzofuran, benzimidazole, benzothiophene, benzisothiazole, benzoxazole, benzisoxazole, pyridoimidazole, pyrimidoimidazole, quinoline, quinoxaline, quinazoline, phthalazine, cinnoline and naphthyridine. Particular optional substituents for alkyl, phenyl (and phenyl containing portions) and the naphthyl groups and the ring of carbon atoms in the heteroaryl ring (mono or bicyclic) in R14p, R15p, Ri and AR include halo, C1- alkyl 4, hydroxy, nitro, carbamoyl, C 1-4 alkylcarbamsyl, di- (C? 4 alkyl) carbamoyl, cyano, trifluoromethyl, trifluoromethoxy, amino, C? _ Alkylamino, di (C? -4 alkyl) amino, alkyl of C? _4 S (0) q- (q is 0, 1 or 2), carboxy, C 1-4 alkoxycarbonyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-4 alkanoyl, C alkoxy ? 4, C 1-4 alkyl (0) 2 amino, C 1-4 alkanoylamino, benzoylamino, benzoyl, phenyl (optionally substituted by up to three substituents selected from halo, C 1-4 alkoxy or cyano), furan, pyrrole, pyrazole, imidazole, triazole, pyrimidine, pyridazine, pyridine, isoxazole, oxazole, isothiazole, thiazole, thiophene, hydroxyimino-C? _4 alkyl, C? _4-C4_4 alkoxyimino, C? _4 hydroxyalkyl, halo o C 4 alkyl, 4 C 4 nitroalkyl, 4 C 4 aminoalkyl, C 4 4 cyanoalkyl >; C 1-4 alkylsulfonamido, aminosulfonyl, C 1-4 alkylaminosulfonyl and di- (C 1-4 alkyl) aminosulfonyl. The phenyl and naphthyl groups and the heteroaryl rings (mono- or bicyclic) in R 4P, Ri and AR can be mono- or di-substituted on those of carbon atoms in the ring with substituents independently selected from the above list of substituents special options. In this specification the term 'alkyl' includes straight chain and branched structures. For example, C6 -6 alkyl includes propyl, isopropyl and tert-butyl. However, references to individual alkyl groups such as "propyl" are specific for only the chained linear version, and with reference to branched individual alkyl groups such as "isopropyl" are specific for only the branched chain version. A similar convention applies to other radicals, for example C1-4 haloalkyl including 1-bromoethyl and 2-bromoethyl.

There are particular and adequate following values for certain substituents and groups referred to in this specification. These values can be used when appropriate with any of the definitions and modalities described in the above or in the following. Examples of C 1 -4 alkyl and C 1 -5 alkyl include methyl, ethyl, and propyl and isopropyl; examples of C? _6 alkyl include methyl, ethyl, propyl, isopropyl, pentyl and hexyl; examples of C? _10 alkyl include methyl, ethyl, propyl, isopropyl, pentyl, hexyl, heptyl, octyl and nonyl; examples of C? -4-alkylamino of C? _4 include formamidomethyl, acetamidomethyl and acetamidoethyl; examples of C? _4 hydroxyalkyl and C? _6 hydroxyalkyl include hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl and 3-hydroxypropyl; examples of C 4 -4 alkoxycarbonyl include methoxycarbonyl, ethoxycarbonyl and propoxycarbonyl; examples of 2- (C 1-4 alkoxycarbonyl) ethenyl include 2- (methoxycarbonyl) ethenyl and 2- (ethoxycarbonyl) ethenyl; examples of 2-siane-2- (C ?4) alkyl ethenyl include 2-cyano-2-methylethenyl and 2-cyano-2-ethylethenyl; examples of 2-nitro-2- (C 1 -4 alkyl) ethenyl include 2-nitro-2-methylethenyl and 2-nitro-2-ethylethenyl; examples of 2- (C 1-4 alkylamino) ethenyl include 2- (methylaminocarbonyl) ethenyl and 2- (ethylaminocarbonyl) ethenyl; examples of 2- (C2_4 alkyl) alkenyl include allyl and vinyl; examples of C 2-4 alkynyl include ethynyl and 2-propynyl; Alkanoyl examples of C? _4 include formyl, acetyl and propionyl; examples of C 1 -4 alkoxy include methoxy, ethoxy and propoxy; examples of C6-6 alkoxy and C1-10 alkoxy include methoxy, ethoxy, propoxy and pentoxy; examples of C1-4 alkylthio include methylthio and ethylthio; examples of alkylamino d? C1-4 include methylamino, ethylamino and propylamino; examples of di- (C.alkyl) amino include dimethylamino, N-ethyl-N-methylamino, diethylamino, N-methyl-N-propylamino and dipropylamino; examples of halo groups include fluorine, chlorine and bromine; examples of C 1-4 alkylsulfonyl include methylsulfonyl and ethylsulfonyl; examples of C 1-4 alkoxy of C 1-4 alkoxy and C 1-6 alkoxy of C 1-6 alkoxy include methoxymethoxy, 2-methoxyethoxy, 2-ethoxyethoxy and 3-methoxypropoxy; examples of C? -4-alkoxy of C? -4-alkoxy of C? _4 include 2- (methoxymethoxy) ethoxy, 2- (2-methoxyethoxy) ethoxy; 3- (2-methoxyethoxy) propoxy and 2- (2-ethoxyethoxy) ethoxy; examples of C1-4S (0) 2-amino alkyl include methylsulfonylamino and ethylsulfonylamino; examples of C 1-4 alkanoylamino and C 1-4 alkanoylamino include formamido, acetamido and propionylamino; examples of C4_4 alkoxycarbonylamino include methoxycarbonylamino and ethoxycarbonylamino; Examples N- C 1-4-N-alkanoylamino of C? _6 include N-methylacetamido, N-ethylacetamido and N-methylpropionamido; examples of C 1-4 alkyl (O) pNH- wherein p is 1 or 2 include methylsulfinylamino, methylsulfonylamino, ethylsulfinylamino and ethylsulphonylamino; Examples of alkyl C1.-4S (O) p (C _4 alkyl?) N- wherein p is 1 or 2 include metilsulfinilmetilamino, metilsulfonilmetilamino, 2- (ethylsulfinyl} ethylamino and 2- (ethylsulfonyl) ethylamino;.. Examples fluoroalkyl of C1-4S (O) pNH- wherein p is 1 or 2 include t'rifluorometilsulfinilamino and trifluoromethylsulfonylamino;? examples of fluoroalkyl _4S C (O) p (? C _4 alkyl) NH- wherein p is 1 or 2 includes trifluorometilsulfinilmetilamino and trifluorometilsulfonilmetilamino;? examples of alkoxy C (hydroxy) orilo will include methoxy (hydroxy) phosphoryl and ethoxy (hydroxy) phosphoryl; examples of di-C1-4 alkoxyphosphoryl include di-of metoxifosforilo, di-etoxifosforilo and ethoxy (methoxy) phosphoryl;? examples of alkyl -4S C (0) q- wherein q is 0, 1 or 2 include methylthio, ethylthio, methylsulfinyl, ethylsulfinyl, methylsulfonyl and ethylsulfonyl; examples of phenyl S (O) q naphthyl S (0) q-; where q is 0, 1 or 2 are phenylthio, phenylsulfinyl, phenylsulfonyl and naphthylthio, naphthylsul finyl and naphthylsulfonyl respectively; examples of benzyloxy-C 4 alkyl include benzyloxymethyl and benzyloxyethyl; examples of a C3-4 alkylene chain are trimethylene or tetramethylene;examples of C? -6-C6-alkyl-6alkyl include methoxymethyl, ethoxymethyl and 2-methoxyethyl; examples of C2-6 hydroxy-alkoxy include 2-hydroxyethoxy and 3-hydroxypropoxy; Examples of C? -4-C alco -4 alkylamino of C 2-6 alkoxy include 2-methylaminoethoxy and 2-ethylaminoethoxy; examples of C 2-6 alkylamino of C 2-6 alkoxy include 2-dimethylamino ethoxy and 2-diethylamino ethoxy; examples of phenylalkyl of C? _ include benzyl and phenethyl; examples of C1-4 alkylcarbamoyl include methylcarbamoyl and ethylcarbamoyl; examples of di (C 1-4 alkyl) carbamoyl include di (methyl) carbamoyl and di (ethyl) carbamoyl; examples of hydroxyiminoC 1-4 alkyl include hydroxyiminomethyl, 2- (hydroxyimino) ethyl and 1- (hydroxyimino) ethyl; Examples of C 4 -4 alkoxyimino C 4 alkyl include methoxyiminomethyl, ethoxyiminomethyl, 1- (methoxyimino) ethyl and 2- (methoxyimino) ethyl; Examples of haloalkyl of C? _4 include, halomethyl, 1-haloethyl, 2-haloethyl, and 3-halopropyl; examples of nitroalkyl of C? _4 include nitromethyl, 1-nitroethyl, 2-nitroethyl and 3-nitropropyl; Examples of C1-aminoalkyl include aminomethyl, 1-a-inoethyl, 2-aminoethyl and 3-aminopropyl; examples of cyanoalkyl of C? _ include cyanomethyl, 1-cyanoethyl, 2-cyanoethyl and 3-cyanopropyl; examples of C.sub.1-4 alkanesulfonamido include methanesulfonamido and ethanesulfonamido; examples of C 1-4 alkylaminosulfonyl include methylaminosulfonyl and ethylaminosulfonyl; and examples of C 1-4 di-alkylaminosulfonyl include dimethylaminosulfonyl, diethylaminosulfonyl and N-methyl-N-ethylaminosulfonyl; examples of C 1-4 alkanesulfonyloxy include methylsulfonyloxy, ethylsulfonyloxy and propylsulfonyloxy; examples of C? _4 alkanoyloxy include acetoxy; examples of C4_4 alkylaminocarbonyl include methylaminocarbonyl and ethylaminocarbonyl; examples of di (C? _4) aminosarbonyl alkyl include dimethylaminocarbonyl and diethylaminocarbonyl; examples of cycloalkyl of Q3-8 include cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl; examples of C4_7 cycloalkyl include cyclobutyl, cyclopentyl and cyclohexyl; examples of di (N-C 1-4 alkyl) aminomethylimino include dimethylaminomethylimino and diethylaminomethylimino. Particular values for AR2 include, for example, for those AR2 containing a heteroatom, furan, pyrrole, thiophene; for those AR2 containing one to four N atoms, pyrazole, imidazole, pyridine, pyrimidine, pyrazine, pyridazine, 1,2,3- and 1,2,4-triazole and tetrazole; for those AR2 that contain an atom of N and one of O, oxazole, isoxazole and oxazine; for those AR2 which contain an N atom and an S atom, thiazole and isothiazole; for those AR2 that contain two atoms of N and one of S, 1,2,4- and 1,3,4 thiadiazole. Particular examples of AR2a include, for example, dihydropyrrole (especially 2,5-dihydropyrrol-4-yl) and tetrahydropyridine (especially 1,2,5,6-tetrahydropyrid-4-yl). Particular examples of AR2b include, for example, tetrahydrofuran, pyrrolidine, morpholine (preferably morpholino), thiomorpholino (preferably thiomorpholino), piperazine (preferably piperazine), imidazoline and piperidine, 1,3-dioxolan-4-yl, 1, 3- dioxan-4-yl, 1,3-dioxan-5-yl and 1,4-dioxan-2-yl. Particular values for AR3 include, for example, benzofused bicyclic systems containing a 5- or 6- membered heteroaryl ring containing a nitrogen atom and optionally 1-3 additional heteroatoms selected from oxygen, sulfur and nitrogen. Specific examples of ring systems include, for example, indole, benzofuran, benzothiophene, benzimidazole, benzothiazole, benzisothiazole, benzoxazole, benzisoxazole, quinsoline, quinoxaline, quinazoline, phthalazine and cinnoline. Other particular examples of AR3 include 5 / 5-, 5/6 and 6/6 bicyclic ring systems containing heteroatoms in both of the rings. Specific examples of such ring systems include, for example, purine and naphthyridine. Additional particular examples of AR3 include bicyclic heteroaryl ring systems with at least one bridgehead nitrogen and optionally 1-3 additional heteroatoms selected from oxygen, sulfur and nitrogen. Specific examples of such ring systems include, for example, 3H-pyrrolo [1,2-a] pyrrole, pyrrolo [2, 1-b] thiazole, 1H-imidazo [1, 2-a] pyrrole, lH- imidazo [1, 2-a] imidazole, 1H, 3H-pyrrolo [1,2-c] oxazole, 1H-imidazo [1, 5-a] pyrrole, pyrrolo [1,2-b] isoxazole, imidazo [ 5, lb] thiazole, imidazo [2, 1-b] thiazole, indolizine, imidazo [1,2-a] pyridine, imidazo [1,5-a] pyridine, pyrazolo [1,5-a] pyridine, pyrrolo [ 1, 2-b] pyridazine, pyrrolo [1, 2-c] pyrimidine, pyrrolo [1,2-a] pyrazine, pyrrolo [1,2-a] pyrimidine, pyrido [2, lc] -s-triazole, s -triazol [1, 5-a] pyridine, imidazo [1,2-c] pyrimidine, imidazo [1,2-a] pyrazine, imidazo [1,2-a] pyrimidine, imidazo [1,5-a] pyrazine , imidazo [1, 5-a] pyrimidine, imidazo [1,2-b] pyridazine, s-triazolo [4, 3-a] pyrimidine, imida-zo [5, 1-b] oxazole and imidazo [2, 1 -b] oxazole. Other specific examples of such ring systems include, for example, 1 [H] -pyrrolo [2, 1-c] oxazine, [3 H] -oxazolo [3, 4-a] pyridine, [6H] -pyrrolo [2, 1-c] oxazine and pyrido [2, lc] [1,4] oxazine. Other specific examples of the 5/5 bicyclic ring systems are imidazooxazole or imidazothiazole, in particular imidazo [5, 1-b] thiazole, imidazo [2, 1-b] thiazole, imidazo [5, 1-b] oxazole or imidazo [2, 1-b] oxazole. Particular examples of AR3a and AR3b include, for example, indoline, 1, 3, 4, 6, 9, 9a-hexahydropyrido [2, lc] [1,4] oxacin-8-yl, 1,2,3 , 5,8,8a-hexahydroimidazo- [1, 5a] pyridin-7-yl, 1,5,8,8a-tetrahydrooxazol [3, 4a] pyridin-7-yl, 1,5,6,7,8, 8a-hexahydrooxazolo [3, 4a] pyridin-7-yl, (7aS) [3H, 5H] -1, 7a-dihydropyrrolo [1,2c] oxazol-6-yl, '(7aS) [5H] -1, 2 , 3, 7a- tetrahydropyrrolo [1, 2c] imidazol-6-yl, (7aR) [3 H, 5H] -l, 7a-dihydropyrrolo [l, 2c] oxazol-6-yl, [3 H, 5 H] -pyrrolo [1,2-c] oxazol-6-yl, [5H] -2 , 3-dihydropyrrolo [1, 2-c] i-midazol-6-yl, [3 H, 5 H] -pyrrolo [1, 2-c] thiazol-6-yl, [3 H, 5 H] -1,7a-dihydropyrrolo [1, 2-c] thiazol-6-yl, [5H] pyrrolo [1,2-c] imidazol-6-yl, [1 H] -3,4,8,8a-tetrahydropyrrolo [2, 1- c] oxacin-7-yl, [3 H] -1, 5, 8, 8a-tetrahydrooxazolo [3,4-a] pyrid-7-yl, [3 H] -5,8-dihydroxazolo [3, 4-a] pyrid- 7-yl and 5,8-dihydroimidazo [1, 5-a] pyrid-7-yl. Particular values for AR4 include, for example, pyrrolo [a] quinoline, 2,3-pyrroloisoquinoline, pyrrolo [a] isoquinoline, lH-pyrrolo [1,2-a] benzimidazole, 9H-imidazo [1,2-a] indole, 5H-imidazo [2, 1-a] isoindol, 1H-i idazo [3, 4-a] indole, imidazo [1, 2-a] quinoline, imidazo [2, la] isoquinoline, imidazo [1, 5 -a] quinoline and imidazo [5,1-a] isoquinoline. The nomenclature used is that found in, for example, "Heterocyclic Compounds (systems with bridgehead nitrogen), WL Mosby (Intercsience Publishers Inc., New York), 1961, parts 1 and 2. Where the optional substituents are listed such Substitution is preferably without geminal disubstitution unless otherwise stated.If not otherwise stated, the optional substituents for a particular group are those set forth for similar groups herein The appropriate substituents on AR1, AR2 , AR2a, AR2b, AR3, AR3a, AR3b, AR4, AR4a, CY1 and CY2 are (on an available carbon atom) up to three substituents independently selected from C ?4 alkyl, optionally substituted by (preferably one) substituents independently selected from hydroxy, trifluoromethyl, C? -4S (0) q- (q is 0 1, or 2) alkyl (the latter substituent preferably in ARl only), C? -4 alkoxy, alkoxycarbonyl, cyano, nitro, alkanoylamino of C? _4, -CONRvRw or NRvRw} , trifluoromethyl, hydroxy, halo, nitro, cyano, thiol, C? -4 alkoxy, C? -4 alkanoyloxy, dimethylaminomethyleneaminocarbonyl, di (C? _4) N aminomethylimino, carboxy, C? _4 alkoxycarbonyl, alkanoyl of C? _4, C? -4S02amino alkyl, C2_4 alkenyl. { optionally substituted by carboxy or alkoxycarbonyl of C? _4} , C 2-4 alkynyl, C 1-4 alkanoylamino, oxo (= 0), thioxo (= S), C 1-4 alkanoylamino. { the C1-4 alkanoyl group being optionally substituted by hydroxy} , Ci-4S alkyl (0) q- (q is 0, 1 or 2). { the C1-4 alkyl group being optionally substituted by one or more groups independently selected from cyano, hydroxy and C1-4 alkoxy} , -CONRvRw or -NRvRw [wherein Rv is hydrogen or C? _ Alkyl; Rw is hydrogen or C? _4 alkyl]. Additional suitable substituents on AR1, AR2, AR2a, AR2b, AR3, AR3a, AR3b, AR4, AR4a, CY1 and CY2 (at the available carbon atom), and also on the alkyl groups (unless otherwise indicated) way) up to three substituents independently selected from trifluoromethoxy, benzoylamino, benzoyl, phenyl. { optionally substituted by up to three substituents independently selected from halo, C 1-4 alkoxy or cyano} , furan, pyrrole, pyrazole, imidazole, triazole, pyrimidine, pyridazine, pyridine, isoxazole, oxazole, isothiazole, thiazole, thiophene, hydroxyimino-C-4-alkyl, C 1-4 -alkoxyimino-C 1-4 -alkyl , haloalkyl of C 1-4, alkylsulfonamido of C? _4, -S02NRvRw [wherein Rv is hydrogen or C? _4 alkyl; Rw is hydrogen or C1-4 alkyl]. Preferred optional substituents on Ar2b such as 1,3-dioxolan-4-yl, 1,3-dioxan-4-yl, 1,3-dioxan-5-yl or 1,4-dioxan-2-yl are mono- or disubstituted by substituents independently selected from C 1 -4 alkyl (including geminal disubstitution), C 1-4 alkoxy, C 1-4 alkylthio, acetamido, C 1-4 alkanoyl, cyano, trifluoromethyl and phenyl]. Preferred optional substituents on CYl and CY2 are mono- or disubstituted by substituents independently selected from C? - alkyl (including geminal disubstitution), hydroxy, C? 4, C 1-4 alkylthio, acetamido, C 1-4 alkanoyl, cyano, and trifluoromethyl. Suitable substituents on AR2, AR2a, AR2b, AR3, AR3a, AR3b, AR4 and AR4a are (at an available nitrogen atom, where such substitution does not result in quaternization) C1-4 alkyl, C4 alkanoyl. { wherein the C1-4 alkyl, and C1-4 alkanoyl groups are optionally substituted by (one preferably) substituents independently selected from cyano, hydroxy, nitro, trifluoromethyl, C? -4S (0) q- alkyl ( q is 0, 1 or 2), C 1-4 alkoxy, C 1-4 alkoxycarbonyl, C 1-4 alkanoylamino, -CONRvRw or -NRvRw [wherein Rv is hydrogen or C? _ alkyl; Rw is hydrogen or C? _] Alkyl} , C2-4 alkenyl, C4 alkynyl, C4 alkoxycarbonyl or oxo (to form an N-oxide). Suitable pharmaceutically acceptable salts include acid addition salts such as methanesulfonate, fumarate, hydrochloride, citrate, maleate, tartrate and (less preferable) hydrobromide. Also suitable are salts formed with phosphoric and sulfuric acid. In another aspect suitable salts are base salts such an alkali metal salt, for example sodium, or an alkaline earth metal salt, for example calcium or magnesium, an organic amine salt for example triethylamine, morpholine, N-methylpiperidine, N- ethylpiperidine, procaine, dibenzylamine, N, N-dibenzylethylamine, tris- (2-hydroxyethyl) amino, N-methyl d-glucamine and amino acids such as lysine. It can be more than one cation or anion depending on the number of charged functions and the valence of the cations or anions. A preferable pharmaceutically acceptable salt is the sodium salt. However, to facilitate the isolation of the salt during the preparation, salts that are less soluble in the selected solvent may be preferred if they are pharmaceutically acceptable or not.

The compounds of the formula (I) can be administered in the form of a prodrug that is destroyed in the human or animal body to give a compound of the formula (I) A prodrug can be used to alter or improve the physical and / or pharmacokinetic profile of the parent compound and can be formed when the parent compound contains a suitable group or substituent that can be derivatized to form a prodrug. Examples of prodrugs include in vivo hydrolysable esters of a compound of the formula (I) or a pharmaceutically acceptable salt thereof. Various forms of prodrugs are known in the art, for examples see: a) Desing of Prodrugs, edited by Bundgaard, (Elsevier, 1985) and Methods in Enzymology, Vol. 42, p. 309-396, edited by K. Widder, et al. (Academic Press, 1985); b) A Textbook of Drug Desing and Development, edited by Krogsgaard-Larsen and H. Bundgaard, Chapter 5"Desing and Application of Prodrugs", by H. Bundgaard p.113-191 (1991); c) H. Bundgaard, Advanced Drug Delivery Reviews 8_, 1-38 (1992); d) H. Bundgaard, et al. , Journal of Pharmaceutical Sciences, 77, 285 (1988); and e) N. Kakeya, et al. , Chem Pharm Bull, 32, 692 (1984).

An in vivo hydrolysable ester of a compound of the formula (I) or a pharmaceutically acceptable salt thereof containing the carboxy or hydroxy group, for example, a pharmaceutically acceptable ester which is hydrolyzed in the human or animal body to produce the acid or main alcohol. Suitable pharmaceutically acceptable esters for the carboxy include C?-6 alkoxymethyl esters for example methoxymethyl, C?-6 alkanoyloxymethyl esters eg pivaloyloxymethyl, phthalidyl esters, C3_8 cycloalkoxycarbonyloxy esters of C ?_6 alkyl, 1-cyclohexylcarbonyloxyethyl ester; 1,3-dioxolan-2-onylmethyl esters for example 5-methyl-1,3-dioxolan-2-ylmethyl; and C6_6alkoxycarbonyloxyethyl esters, for example 1-methoxycarbonyloxyethyl and can be formed in any carboxy group in the compounds of this invention. An in vivo hydrolysable ester of a compound of the formula (I) or a pharmaceutically acceptable salt thereof containing a hydroxy group or groups including inorganic esters such as phosphate esters (including cyclic phosphoramide esters) and α-acyloxyalkyl ethers and Related compounds which, as a result of the in vivo hydrolysis of the destroyed ester, give the hydroxytrincipal group / groups. Examples of α-acyloxyalkyl ethers include acetoxymethoxy and, 2-dimethylpropionyloxymethoxy. A selection of the in vivo hydrolysable ester forming groups by hydroxy includes C alca _ ?O, benzoyl, phenylacetyl, benzoyl and phenylacetyl substituted alkanoyl, C alco _ alco alco alkoxycarbonyl (to give alkylcarbonate esters), C di _-alkylcarbamoyl alkanoyl. ? 4 and N- (C? -4) -N-alkylcarbamoyl di-alkylaminoethyl of C? _ (To give carbamates), di-alkylaminoacetyl and carboxyacetyl. Examples of substituents on benzoyl include chloromethyl or aminomethyl, C? _4 alkylaminomethyl and di- (C 1-4 alkyl) aminomethyl, and morpholino or piperazino bonded from a nitrogen atom ring by means of a linking group of methylene to the 3- or 4- position of the benzoyl ring. Certain in vivo hydrolysable esters of a compound of the formula (I) are described within the definitions listed in this specification, for example esters described by the definition (Rc2d), and some groups within (Rc2c). Suitable in vivo hydrolysable esters of a compound of the formula (I) are described as follows. For example, a 1,2-diol can be cyclized to form a cyclic ester of formula (PD1) or a pyrophosphate of the formula (PD2): (PD1) (PD2) Particularly interesting are those prodrugs cyclized when the 1,2-diol is on an alkyl chain of C_4 bonded to a carbonyl group in a substituent of the formula Rc supported by a nitrogen atom in (TC4). The esters of the compounds of the formula (I) wherein the function or functions HO- in (PD1) and (PD2) are protected by C? _4 alkyl, phenyl or benzyl are useful intermediates for the preparation of such prodrugs. Additional in vivo hydrolysable esters include phosphoramide esters, and also compounds of formula (I) in which any free hydroxy group independently forms a phosphoryl ester (npd is 1) or phosphoryl ester (npd is O) of the formula (PD3): ( 0) npd II HO / O HO (PD3) Intermediates useful for the preparation of such esters include compounds which contain a group or groups of the formula (PD3) in which either or both of the -OH groups in (PD3) is independently protected by C 1-4 alkyl (such compounds are also interesting compounds per se), phenyl or phenyl-C 1-4 alkyl (such phenyl groups optionally substituted by 1 or 2 groups independently selected from C 1-4 alkyl, nitro, halo and C 1-4 alkoxy Thus, prodrugs containing the groups such as (PDl), (PD2) and (PD3) can be prepared by the reaction of a compound of the formula (I) containing the group or suitable hydroxy groups with a suitably protected phosphorylating agent (eg, containing a chloro or dialkylamino leaving group), followed by oxidation (if necessary) and deprotection When a compound of the formula (I) contains a number of hydroxy group l ibre, those groups are not converted into a prodrug functionality that can be protected (e.g., using a t-butyl-dimethylsilyl group), and the latter deprotected. Also, enzymatic methods can be used for selectively phosphorylated or dephosphorylated alcohol functionalities. Other interesting in vivo hydrolysable esters include, for example, those in which Rc was defined by, for example, R14C (0) O-C6-6-C0 alkyl (wherein R14 is, for example, benzyloxy-C-alkyl? _4, or phenyl Suitable substituents on a phenyl group in such esters include, for example, 4-piperazino of C4_4-C4_4alkyl, piperazino-C4_4alkyl and morpholino-C4_4alkyl. Where pharmaceutically acceptable salts of an in vivo hydrolysable ester can be formed, this is achieved by conventional techniques In this way, for example, the compounds containing a group of the formula (PD1), (PD2) and / or ( PD3) can ionize (partially or completely) to form salts with an appropriate number of counter-ions.Thus, by way of example, if an in vivo hydrolysable ester prodrug of a compound of formula (I) contains two groups ( PD3), there are four HO-P functionalities present in the total molecule, each of which The salts can form an appropriate salt (ie, the total molecule can form, for example, a mono-, di-, tri- or tetra-sodium salt. The compounds of the present invention have a chiral center at the C-5 position of the oxazolidinone ring. The pharmaceutically active enantiomer is of the formula IA): (A) The present invention includes the pure enantiomer represented in the above or mixtures of the 5R and 5S enantiomers, for example a racemic mixture. If a mixture of enantiomers is used, a large amount (depending on the ratio of the enantiomers) will be required to achieve the same effect as the same weight of the pharmaceutically active enantiomer. For the evasion or doubt of the enantiomer represented in the above is the 5R enantiomer. In addition, some compounds of the formula (I) may have other chiral centers. It is to be understood that the invention encompasses all optical and diastere isomers, and racemic mixtures, which possess antibacterial activity. It is well known in the art how to prepare optically active forms (for example by resolution of the racemic form by recrystallization techniques, by chiral synthesis, by enzymatic resolution, by biotransformation or by chromatographic separation) and how to determine antibacterial activity as described in the next.

The invention relates to all the tautomeric forms of the compounds of the formula (I) which possess antibacterial activity. It will also be understood that certain compounds of the formula (I) can exist in solvated as well as unsolvated forms such as, for example, hydrated forms. It will be understood that the invention encompasses all solvated forms that possess antibacterial activity. It will also be understood that certain compounds of the formula (I) may exhibit polymorphism, and that the invention encompasses all forms possessing antibacterial activity. As stated in the above, a range of compounds having good activity against a wide range of Gram-positive pathogens including organisms known to be resistant to more commonly used antibiotics has been discovered. The physical and / or pharmacokinetic properties are important characteristics, for example, the increased stability to the mammalian peptidase metabolism and a favorable toxicological profile. The following compounds possess particularly favorable and / or pharmacokinetic physical properties and are preferred. Particularly preferred compounds of the invention comprise a compound of formula (I) or formula (IP), or a pharmaceutically acceptable salt or an in vivo hydrolysable ester thereof, wherein the substituents Q, X, HET, T and other substituents mentioned in the above have values described in the foregoing, or any of the following values (which may be used where appropriate with any of the definitions and modalities described in the following or in the foregoing): Preferably Q is selected from Ql , Q2, Q4, Q6 and Q9; especially Q1, Q2 and Q9; more particularly Q1 and Q2; and more preferably Q is Ql. Preferably T is selected from (TAf), (TDb) or (TC); the groups especially (TCb) and (TCc); more particularly (TC2), (TC3) and (TC4); and more preferably (TC5), (TC7) or (TC9), and more particularly (TC5). Especially preferred is each of these values of T when present in Q1 and Q2, particularly in Q1. Preferred values for other substituents (which may be used where appropriate with any of the definitions and embodiments described in the foregoing or the following) are: - (a) Preferably X is -0-; (al) In another aspect X is -S-; (a2) In another embodiment X may also be -SO- or -S02-; (b) Preferably HET is pyridine, pyridazine or pyrazine; more preferably HET is pyridin-2-yl, pyridazin-3-yl or pyrazin-2-yl; (bl) Preferably HET is unsubstituted; (c) Preferably Rp is hydrogen; (d) Preferably Rpl 'and Rp2 are independently selected from hydrogen, C? _4 alkyl, carboxy, C? -4 alkoxycarbonyl, hydroxymethyl, C? -4 alkoxymethyl or carbamoyl; (e) More preferably Rpl and Rp2 are hydrogen; (f) Preferably one of R2 and R3 is hydrogen and the other fluorine; (g) In another aspect both R2 and R3 are fluorine; (h) Preferably > A-B- is of the formula > C = CH- (ie Rr is preferably hydrogen) or > N-CH2-; (i) Preferably D is -0- or > NRcp; (j) Preferably Rep is AR, R13pC0-, R13pS02-, R13pCS-; (k) More preferably Rep is AR (more preferably b'encyl, pyrimidyl, pyridinyl, pyridazinyl, or pyrazinyl) or R13pC0- (especially R13pCO-); (1) Preferably AR is 5- or 6-membered heteroaryl, more preferably AR is 6-membered heteroaryl, such as pyridinyl; (m) Preferred substituents for phenyl and carbon atoms in the heteroaryl ring systems (mono- and bicyclic) in AR, AR14p and Ri include halo, C? _4 alkyl, hydroxy, nitro, amino, cyano, C-alkyl ? 4 S (0) p- and C? _4 alkoxy. (n) Preferably ring systems optionally substituted on AR, R14p and Ri are unsubstituted; (ni) In another embodiment in the definition of R13p (PC) of the mode (IP), 1,3-dioxolan-4-yl and 1,4-dioxan-2-yl are excluded. (o) Preferably R13p is C? _4 alkoxycarbonyl, C? _4 hydroxyalkyl, C? -4 -4 alkyl (optionally substituted by one or two hydroxy groups, or by a C-4-4 alkanoyl group, C alqu alqu alkylamino) ? -4 / dimethylamino-C? _ Alkyl, C1-4 alkoxymethyl, C? _4 alkanoylmethyl, C? -4 alkanoyloxy-C1-4 alkyl, C1-5 alkoxy or 2-cyanoethyl; (p) More preferably R13p is 1,2-dihydroxyethyl, 1,3-dihydroxyprop-2-yl, 1,2,3-trihydroxyprop-1-yl, methoxycarbonyl, hydroxymethyl, methyl, methylamino, dimethylaminomethyl, methoxymethyl, acetoxymethyl, methoxy , methylthio, naphthyl, tert-butoxy or 2-cyanoethyl; (pl) Even more preferably R13p is 1,2-dihydroxyethyl, 1,3-dihydroxyprop-2-yl or 1,2,3-trihydroxyprop-1-yl; (q) Preferred optional substituents for alkyl of Ci-xo, in R14p are hydroxy, cyano, amino, alkylamino of C? 4, C?-4-amino di-alkyl, C? -4-S-((0) p- alkyl (wherein p is 1 or 2), carboxy, C 1 -4 alkoxycarbonyl, C? _4 alkoxy, piperazine or morpholino; (r) Optional substituents for C1-6alkyl in R15p are hydroxy, C4-4alkoxy, cyano, amino, C1-4alkylamino, di (C2_2) aminoalkyl, C4-4alkyl S (0) p- (where p is 1 or 2); (s) Preferably 5- or 6- membered heteroaryl in R 14p is pyridinyl or imidazol-1-yl; (t) Preferably R15p is C? _6 alkyl; more preferably R15p is tert-butyl or methyl; (u) Preferably R17p is cyano or fluorine; (v) Preferably R16p is hydrogen; (w) Preferably CY is naphthoxy, especially naphth-1-oxy or naphth-2-oxy. When the preferred values are given for substituents in a compound of the formula (IP), the corresponding substituents in a compound of the formula (I) have the same preferred values (i.e., for example, R13 and Rc in the formula (I ) correspond to Rep and R13p in the formula (IP), and similarly for groups D and G). The compounds of the preferred values of the formula (I) for Rc are those in the group (Rc2). The preferred values for R13p listed above for the compounds of the formula (IP) are also preferred values for R13 in compounds of the formula (I). In the definition of (Rc2c) the AR2a, AR2b, AR3a and AR3b versions of AR2 and AR3 contain groups that are preferably excluded. The especially preferred compounds of the present invention are of the formula (IB): (IB) wherein HET is pyridin-2-yl or pyrazin-2-yl (especially pyridin-2-yl); R2 and R3 are independently hydrogen or fluorine; and Rpl and Rp2 are independently hydrogen, hydroxy, bromine, C? _4 alkyl, carboxy, C? _4 alkoxycarbonyl, hydroxymethyl, C? _ alkoxymethyl or carbamoyl; or pharmaceutically acceptable salts thereof. In addition, the especially preferred compounds of the invention are of the formula (IB) wherein HET is pyridin-2-yl or pyrazin-2-yl (especially pyridin-2-yl); R2 and R3 are independently hydrogen or fluorine; and Rpl and Rp2 are independently hydrogen, AR-oxymethyl or AR-thiomethyl (wherein AR is phenyl, phenylalkyl of C? _4, naphthyl, furan, pyrrole, pyrazole, imidazole, triazole, pyrimidine, pyridazine, pyridine, isoxazole, oxazole, isothiazole, thiazole or thiophene); or pharmaceutically acceptable salts thereof. Of the above especially preferred compounds of the invention of the formula (IB), the particularly preferred compounds are those wherein Rpl and Rp2 are hydrogen being particularly preferred. In addition, the especially preferred compounds of the invention are of the formula (IC): (IC) wherein HET is pyridin-2-yl or piazin-2-yl (especially pyridin-2-yl); R2 and R3 are independently hydrogen or fluorine; Rpl and Rp2 are independently hydrogen, AR-oxymethyl or AR-thiomethyl (where AR is phenyl, phenylalkyl of C -4 -4, naphthyl, furan, pyrrole, pyrazole, imidazole, triazole, pyrimidine, pyrimidazine, pyridine, isoxazole, oxazole, isothiazole , thiazole or thiophene), C 4 alkyl, carboxy, C 1-4 alkoxycarbonyl, hydroxymethyl, C 1-4 alkoxymethyl or carbamoyl and Rep is cyano, pyrimidine-2-yl, 2-cyanoethyl, 2-cyano-2- C? -4-ethenyl or Rep alkyl is of the formula R13pco-, R13pS02- or R13pCS- (wherein R13p is hydrogen, C1-5 alkyl [optionally substituted by one or more groups each independently selected from hydroxy and amino , or optionally monosubstituted by C 1-4 alkoxy, C? _4S (0) q- alkyl, C 1-4 alkylamino, C 1-4 alkanoyl, naphthoxy, C 2-6 alkanoylamino or C? -4S alkyl ( 0) pNH-where p is 1 or 2 and q is' 0, 1 or 2] imidazole, triazole, pyrimidine, pyridazine, pyridine, isoxazole, oxazole, isothiazole, thiazole, pyrimidazole, pyrimidoimidazole, quinoxaline, quinazoline, f talazine, cinnoline or naphthyridine, or R13p is of the formula R14pC (0) Oalkyl of C? _6 wherein R14p is C? _6 alkyl, or Rep is of the formula RfC (= 0) C (= 0) - wherein Rf is Ci-e alkoxy; or pharmaceutically acceptable salts thereof. Of the above especially preferred compounds of the invention of the formula (IC) those in which HET is pyridin-2-yl or pyrazyl-2-yl (especially pyridin-2-yl); R2 and R3 are independently hydrogen or fluorine; Rpl and Rp2 are independently hydrogen, AR-oxymethyl or ar-thiomethyl (wherein AR is phenyl, phenylalkyl of C4-4, naphthyl, furan, pyrrole, pyrazole, imidazole, triazole, irimidine, iridazine, pyridine, isoxazole, isothiazole , thiazole or thiophene, C 1-4 alkyl, carboxy, C 1-4 alkoxycarbonyl, hydroxymethyl, C 1-4 alkoxymethyl or carbamoyl and Rep is cyano, pyrimidin-2-yl, 2-cyanoethyl, 2-cyano- 2-C?-Ethenyl alkyl or Rep is of the formula R 13pC0-, R 13pCS- (wherein R 13p is hydrogen, (C 1-5 alkyl [optionally substituted by one or more groups each independently selected from hydroxy and amino, optionally monosubstituted by C 1-4 alkoxy, C 1-4 alkyl (0) q, C 1-4 alkylamino, C 1-4 alkanoyl, C 2-6 alkanoylamino or C? -4S (0) pNH- alkyl wherein p is 1 or 2 and q is 0, 1 or 2] pyridine, or R13p is of the formula R14pC (0) Oalkyl of C? _6 wherein R14p is C? -6 alkyl, or Rep is of the formula RfC (= 0) C ( = 0) - where Rf is C6_6 alkoxy; Pharmaceutically acceptable alcohols thereof are further preferred. Of the especially preferred compounds of the invention of the formula (IC), particularly the preferred compounds are those wherein HET is pyridin-2-yl or pyrazin-2-yl (especially pyridin-2-yl); R2 and R3 are independently hydrogen or fluoro; Rpl and Rp2 are hydrogen, and Rep is pyridin-2-yl (optionally substituted with cyano) or Rep is of the formula R13pC0- (wherein R13p is hydrogen, 1,3-dioxolan-4-yl (optionally disubstituted with (C 1-4 alkyl or C 1-5 alkyl [optionally substituted by one or more hydroxy groups] or R 13p is of the formula R 14pC (O) C? _6 alkyl wherein R 14p is C? _4 alkyl); or pharmaceutically acceptable salts thereof. Of the above especially preferred compo of the invention of the formula (IC), the particularly preferred compo are those in which Rep is of the formula R13pCO- (wherein R13p is hydrogen, 1,3-dioxolan-4-yl (optionally disubstituted with C? _4 alkyl) or C? -5 alkyl [substituted by two hydroxy groups], or pharmaceutically acceptable salts thereof In another aspect of the invention are preferred compo provided of the formula (IP) wherein -X -HET is pyridin-2-yloxy or pyrazin-2-yloxy; > AB- es > N-CH2- and D is NRcp wherein Rep is a 6-membered heteroaryl ring containing 1, 2, or 3 rings of atoms of nitrogen as the only ring heteroatoms, bonded by means of a carbon atom ring and optionally substituted on a carbon atom ring by one, two or three substituents independently selected from C? -4 alquiloalkyl, halo, trifluoromethyl, alkyl of C? _S (0) q- (where q is 0, 1 or 2), C 1-4 S (O) 2-amino alkyl, C 1-4 alkanoylamino, carboxy, hydroxy, amino, C? _4 alkylamino, C? _4 -alkylamino, C? _4 alkoxycarbonyl, carbamoyl, N-alkylcarbamoyl C ? _4, di- (N-C4_4alkyl) alkylcarbamoyl, C? _4 cyano or nitro alkoxy; or pharmaceutically acceptable salts thereof.

Another aspect of the invention is as described in the paragraph immediately quoted above, but with -X-HET as pyridazin-3-yloxy. In both of the two paragraphs Rep is preferably a 6-membered heteroaryl ring containing 1 or 2 nitrogen atom rings, and is preferably substituted by cyano. In all of the above aspects and the preferred compo of the formula (IB) or (IC), hydrolysable esters in vivo are preferred, especially phosphoryl esters (as defined by the formula (PD3) with a composuch as 1). In all the above definitions the preferred compo are as shown in formula (IA), ie the pharmaceutically active enantiomer (5 (R)). Particular compo of the present invention include the following (and the individual isomers in which a mixture of isomers is possible): The particular compo of the present invention include: - 5 (R) -Pyrid-2-yloxymethyl-3- ( 4- (4- (5-cyanopyrid-2-yl) piperazin-1-yl) -3-fluorophenyl) oxazolidin-2-one; 5 (R) - (6-chloropyridazin-3- (4- (4- (5-cyanopyrid-2-yl) piperazin-1-yl) -3-fluorophenyl) oxazolidin-2-one; (R) -Pirazin-2-yloxymethyl-3- (4- (4- (5-cyanopyrid-2-yl) piperazin-1-yl) -3-fluorophenyl) oxazolidin-2-one; 5 (R) -Pyrimidin-4-yloxymethyl-3- (4- (4- (5-cyanopyrid-2-yl) piperazin-1-yl) -3-fluorophenyl) oxazolidin-2-one; 5 (R) -Pyridazin-3-yloxymethyl-3- (4- (4- (5-cyanopyrid-2-yl) piperazin-1-yl) -3-fluorophenyl) oxazolidin-2-one; 5 (R) -Pyrid-2-yloxymethyl-3- (3-fluoro-4- (3,6-dihydro- (2H) -pyran-4-yl) phenyl) oxazolidin-2-one; 5 (R) - (4-Methylpyrid-2-yloxymethyl) -3- (3-fluoro-4- (3,6-dihydro- (2H) -pyran-4-yl) phenyl) oxazolidin-2-one; 5 (R) - (3-methylpyrid-2-yloxymethyl) -3- (3-fluoro-4- (3,6-dihydro- (2H) -pyran-4-yl) phenyl) oxazolidin-2-one; 5 (R) - (6-chloropyridazin-3-yloxymethyl) -3- (3-fluoro-4- (3,6-dihydro- (2H) -pyran-4-yl) phenyl) oxazolidin-2-one; 5 (R) -Pyridazin-3-yloxymethyl-3- (3-fluoro-4- (3,6-dihydro- (2H) -pyran-4-yl) phenyl) oxazolidin-2-one; 5 (R) -Pyrimidin-4-yloxymethyl-3- (3-fluoro-4- (3,6-dihydro- (2H) -pyran-4-yl) phenyl) oxazolidin-2-one; 5 (R) -Pirazin-2-yloxymethyl-3- (3-fluoro-4- (3,6-dihydro- (2H) -pyran-4-yl) phenyl) oxazolidin-2-one; 5 (R) - (5-chloropyridin-2-yloxymethyl) -3- (3-fluoro-4- (3,6-dihydro- (2H) -pyran-4-yl) phenyl) oxazolidin-2-one; and pharmaceutically acceptable salts thereof. Of the above particular compo, 5 (R) -Pyrid-2-yloxymethyl-3- (3-fluoro-4- (3,6-dihydro- (2H) -pyran-4-yl) phenyl) oxazolidinone is especially preferred. 2-one; 5 (R) -Pirazin-2-yloxymethyl-3- (3-fluoro-4- (3,6-dihydro- (2H) -pyran-4-yl) phenyl) oxazolidin-2-one; and pharmaceutically acceptable salts thereof. Other preferred compounds are those described in the Examples, and the 3,5-difluorophenyl analogs of the 3-fluorophenyl compounds described in the Examples. Process Section: In a further aspect the present invention provides a process for preparing a compound of the formula (I) or a pharmaceutically acceptable salt or an in vivo hydrolysable ester thereof. It will be appreciated that during certain of the following processes, certain substituents may require protection to prevent their undesirable reaction. The skilled chemist will appreciate when protection is required, and how such protective groups can be put in place, and disposed of later. For examples of protective groups see one of several general texts on the subject, for example, 'Protective Groups in Organic Synthesis' by Theodora Green (publisher: John Wiley &Sons). The protecting groups can be removed by any conventional method as described in the literature or knowledge of the skilled chemist as appropriate for the removal of the protective group in question, such methods are selected as well as affecting the removal of the protective group with minimal alteration. of the groups in another part of the molecule. Thus, if the reagents include, for example, groups such as amino, carboxy or hydroxy, this may be desirable to protect the group in some of the reactions mentioned herein. A suitable protecting group for an amino or alkylamino group is, for example, an acyl group, for example an alkanoyl group such as acetyl, an alkoxycarbonyl group, for example a methoxycarbonyl group, ethoxycarbonyl, or t-butoxycarbonyl, an arylmethoxycarbonyl group, example benzyloxycarbonyl or an aroyl group, for example benzoyl. The. Deprotection conditions for the above protecting groups necessarily vary with the selection of protecting groups. Thus, for example, an acyl group such as an alkanoyl or alkoxycarbonyl group or an aroyl group can be removed, for example, by hydrolysis with a suitable base such as an alkali metal hydroxide, for example lithium or sodium hydroxide. Alternatively an acyl group such as a t-butoxycarbonyl group can be removed, for example, by treatment with a suitable acid such as hydrochloric, sulfuric or phosphoric acid or trifluoroacetic acid and an arylmethoxycarbonyl group such as a benzyloxycarbonyl group can be removed, by example by hydrogenation on a catalyst such as palladium on carbon, or by treatment with a Lewis acid, for example, boron tris (trifluoroacetate). An alternative protecting group suitable for a primary amino group is, for example, a phthaloyl group which can be removed by treatment with an alkylamino, for example, dimethylaminopropylamino or with hydrazine. A suitable protecting group for a hydroxy group is, for example, an acyl group, for example an alkanoyl group such as an acetyl group, an aroyl, for example benzoyl, or an arylmethyl group, for example benzyl. The deprotection conditions for the protecting groups will necessarily vary with the selection of the protecting group. Thus, for example, an acyl group such as an alkanoyl group or an aroyl can be removed, for example, by hydrolysis with a suitable base such as an alkali metal hydroxide, for example lithium or sodium hydroxide. Alternatively, an arylmethyl group such as a benzyl group can be removed, for example, by hydrogenation over a catalyst such as a palladium on carbon. A suitable protecting group for a carboxy group is, for example, an esterification group, for example a methyl or ethyl group which can be removed, for example, by hydrolysis such as a base such as sodium hydroxide, or for example a t-group. -butyl which can be removed, for example, by treatment with an acid, for example an organic acid such as trifluoroacetic acid, or for example a benzyl group which can be removed, for example, by hydrogenation on a catalyst such as palladium on carbon . Examples of the use of resins as a protecting group are illustrated in Examples 135 &; 136 in the present. The protecting groups can be eliminated at any convenient stage in the synthesis using conventional techniques well known in the chemical art. A compound of the formula (I), or a pharmaceutically acceptable salt or an in vivo hydrolysable ester thereof, can be prepared, by any process known to be applicable in the preparation of the chemically related compounds. Such processes, when used to prepare a compound of the formula (I), or a pharmaceutically acceptable salt or an in vivo hydrolysable ester thereof, are provided as a further feature of the invention and are illustrated by the following representative examples. Necessarily the initial materials can be obtained by standard procedures of organic chemistry (see, for example, Advanced Organic Chemistry (Wiley-Interscience), Jerry March). The preparation of such starting materials is described within the attached non-limiting examples. Alternatively, necessarily initial materials are obtainable by procedures analogous to those illustrated that are within the ordinary skill of an organic chemist. The information of the preparation of the necessary initial materials or the related compounds (which can be adapted to form necessary initial materials) can also be found in the following Patent and Application Publications, the contents of the sections of the relevant processes of the which are incorporated herein by reference: WO99 / 02525; W098 / 54161; W097 / 37980; WO97 / 30981 (and US5,736,545); WO97 / 21708 (and US5, 719, 154); WO97 / 10223; W097 / 09328; W096 / 35691; W096 / 23788; WO96 / 15130; WO96 / 13502 WO95 / 25106 (and US5, 668, 286); W095 / 14684 (and US5,652,238) WO95 / 07271 (and US5, 688, 792); W094 / 13649; WO94 / 01110 W093 / 23384 (and US5,547,950 and US5,700,799); WO93 / 09103 (and US5,565,571, US5,654,428, US5,654,435, US5,756,732 and US5,801,246); US5,231,188; US5,247,090; US5,523,403; W097 / 27188; W097 / 30995; W097 / 31917; WO98 / 01447; WO98 / 01446; WO99 / 10342; WO99 / 10343; W099 / 11642; European Patent Application Nos. 0,359,418 and 0,609,9Ü5; 0.693.491 Al (and US5,698,574); 0,694,543 Al (and AU 24985/95); 0,694,544 Al (and CA 2,154,024); 0.697.412 Al (and US5, 529, 998); 0,738,726 Al (and AU 50735/96); 0.785.201 Al (and UA 10123/97); German Patent Application No. DE 195 14 313 Al fy US5, 529, 998); DE 196 01 264 A1 (and AU 10098/97); DE 196 01 265 Al (and UA 10097/97); DE 196 04 223 Al (and AU 12516/97); DE 196 49 095 Al (and AU 12517/97). The following Patent and Application Publications may also provide useful information and the contents of the relevant process sections are hereby incorporated by reference: FR 2458547; FR 2500450 (and GB 2094299, GB 2141716 and US4, 76,136); DE 2923295 (and GB 2028306, GB 2054575, US4,287,351, US4,348,393, US4,413,001, US4,435,415 and US4,526,786), DE 3017499 (and GB 2053196, US4,346,102 and US4, 372, 967); US4,705,799; European Patent Application No. 0,312,000; 0,127,902; 0,184,170; 0.352.781; 0,316,594; The skilled organic chemist will be able to use and adapt the information contained and referred to within the above references to obtain necessary initial materials. Thus, the present invention also provides that the compounds of the formula (I) and the pharmaceutically acceptable salts and the in vivo hydrolysable esters thereof, can be prepared by a process (a) to (g) as follows (in wherein the variables are as defined in the foregoing unless otherwise stated): (a) modifying a substituent on or introducing a substituent on another compound of the formula (I); (b) by the reaction of a compound of the formula (II) O Q- N A O (H) wherein Yp is hydroxy with a compound of the formula (bl) HET-OH or (b2) HET-Lg, wherein Lg is a suitable leaving group; (c) by reacting a compound of the formula (II) wherein Yp is a leaving group, for example halogen, mesylate or tosylate, with a metal alkoxide compound of the formula HET-OM wherein M is an alkali metal , or another metal, such as silver, known to promote 0-alkylation; (d) by the reaction of a compound of the formula Q-Zp wherein Zp is an isocyanate or amine group with an epoxide of the formula CH2 (0) CH-CH20-HET; (e) where X is -S- by an analogous process for processing (c) wherein (the) a metal oxide compound of the formula HET-SM where M is an alkali metal, or other metal, such as silver, known to promote S-alkylation; or (e2) alternatively by an analogous process for processing (c) using HET-SH and a compound of the formula (II) in which Yp is a suitable leaving group; (f) where X is -SO- or -S02- by oxidation of a compound wherein X is -S-; (g) by reacting a urethane compound of the formula (III) with a compound of the formula (IV) (III) (IV) wherein R .21 is C? _6 alkyl or benzyl; and hereinafter if necessary: (i) eliminate any protective groups; (ii) forming a pharmaceutically acceptable salt; (iii) forming a hydrolysable ester in vivo. General guidance on reaction conditions and reagents can be obtained in Advanced Organic Chemistry, 4th Edition, Jerry March (ed.: J. Wiley &Sons), 1992. The necessary initial materials can be obtained by standard chemistry procedures organic, as described in this process section, in the Examples section or by analogous procedures within the ordinary experience of an organic chemist. Certain references are also provided (see above) which describe the preparation of certain suitable starting materials, for particular example see International Patent Application Publication WO 97/37980, the contents of which are incorporated herein by reference. Analogous processes for those described in the references may also be used by the ordinary organic chemist to obtain necessary starting materials. (a) Methods for converting substituents into other substituents known in the art. For example, an alkylthio group can be oxidized to an alkylsulfinyl or alkylsulfonyl group, a cyano group reduced to an amino group, a nitro group reduced to an amino group, an alkylated hydroxy group to a methoxy group, a thiomethylated hydroxy group to an arythiomethyl group or a heteroarylthiomethyl (see, for example, Lett., 585, 1972), a carbonyl group converted to a thiocarbonyl group (for example using the Lawsson reagent) or a bromine group converted to an alkylthio group. It is also possible to convert one Rc group into another Rc group as a final step in the preparation of a compound of the formula (I). A compound of the formula (I) can be converted into another compound of the formula (I) by reacting a compound of the formula (I) in which T is halo with a suitable compound to form another value of T. In this way, for example, T as halo can be displaced by aromatic vinyl, tropolone and nitrogen systems suitable as T by the reaction using known Pd (0) coupling techniques. Additional examples of the substituents converted to other substituents are contained in the appended non-limiting Examples. (bl) When HET-OH is the reaction (bl) used it is carried out under Mitsunobu conditions, for example, in the presence of tri-n-butylphosphine and diethyl azodicarboxylate (DEAD) in an organic solvent such as THF, and in a temperature range from 0 ° C-60 ° C, but preferably at room temperature. The details of the Mitsunobu reactions are contained in Tet. Letts. , 3_1, 699, (1990); The Mitsunobu Reaction, D.L. Hughes, Organic Reactions, 1992, Vol. 42, 335-656 and Progress in the Mitsunobu Reaction, D.L. Hughes, Organic Preparations and Procedures International, 1996, Vol.28, 127-164. (b2) When HET-Lg is the reaction (b2) used, it is carried out using a suitable HET reagent and under basic conditions (using a base such as 1,8-diazabicyclo [5, 4, 0] undec-7-ene) which they are sufficiently smooth do not destroy the structure of the oxazolidinone ring. The skilled organic chemist will appreciate which suitable salient Lg group (such as chlorine or bromine) and reaction conditions to use. The compounds of the formula (II) wherein Yp is hydroxy can be obtained by the reaction of a compound of the formula (III) with a compound of the formula (IV): (III) (IV) wherein R21 is C6-6alkyl or benzyl and R22 is C1-4alkyl or -S (O) C1-4alkyl wherein q is 0, 1 or 2. Preferably R22 is alkyl of C? _4. The compounds of formula (II), (III) and (V) can be prepared by the skilled chemist, for example, as described in International Patent Application Publication Nos. WO98 / 07271, W097 / 27188, WO 97. / 30995, 98/01446 and WO 98/01446, the contents of which are incorporated herein by reference, and by analogous procedures. If no commercially available compound of the formula HET-OH and HET-Lg can be prepared by procedures which are selected from the standard chemical techniques, the techniques which are analogous to the synthesis of the known, structurally similar compounds or techniques which are analogous to the procedures described in the examples. For example, standard chemical techniques are as described in Houben Weyl, Methoden der Organische Chemie. (c) and (e) Reactions (c) and (e) are conveniently carried out at a temperature in the range of 25-60 ° C in a solvent such as NMP or _DMF. A compound of the formula (II) wherein Yp is fluorine can be prepared by reacting a compound of the formula (II) wherein Yp is hydroxy (hydroxy compound) with a fluorinating agent such as diethylaminosulfur trifluoride in an organic solvent such as dichloromethane in the temperature range from 0 ° C to room temperature. When Yp is chloro, the compound of the formula (II) can be formed by reacting the hydroxide compound with a chlorinating agent. For example, by reacting the hydroxy compound with thionyl chloride, in a temperature range from room temperature to reflux, optionally in a chlorinated solvent such as dichloromethane or by reacting the hydroxy compound with carbon tetrachloride / triphenyl phosphino in dichloroethane, in a range of temperature of 0 ° C at room temperature. A compound of the formula (II) when Yp is chloro or iodo can also be prepared from a compound of the formula (II) when Yp is mesylate or tosylate, the latter compound reacting with lithium chloride or lithium iodide and ending with ether , in a suitable organic solvent such as THF in a temperature range from room temperature to reflux. When Yp is C? _4 alkanesulfonyloxy or tosylate, the compound (II) can be prepared by reacting the hydroxy compound with C? -4 alkanesulfonyl chloride or tosyl chloride in the presence of a mild base such as triethylamine or pyridine. The compounds of the formula HET-OM and HET-SM can be prepared by the skilled chemist from the corresponding HET-OH or HET-SH compound, using a suitable base, such as sodium hydride, silver carbonate, sodium carbonate or an alkoxide. When X is -S- and a process that is analogous to process (c) is used but using HET-SH and a compound of formula (II) in which Yp is a suitable leaving group, a suitable leaving group is, for example, Example, mesylate and a suitable base for the reaction, is a base such as 1,8-diazabicylo [5, 4, 0] undec-7-ene (for example, example 153). (d) Reaction (d) is carried out under conditions analogous to those described in the following references which are described as suitable starting materials and the like can be obtained. The compounds of the formula Q-Zp wherein Zp is an isocyanate can be prepared by the skilled chemist, for example by processes analogous to those described in Walter A. Gregory et al in Med. Chem. 1990, 33, 2569-2578 and Chung-Ho Park et al in J. Med. Chem. 1992, 35, 1156-1165. The compounds of the formula Q-Zp is a urethane (see process (i)) can be prepared by the skilled chemist, for example by processes analogous to those described in International Patent Application Publication Nos. WO 97/30995 and WO 97/37980. A reaction similar to reaction (d) can be performed in which Q-Zp where Zp is an amine group is reacted with the epoxide (optionally in the presence of an organic base), and the product is reacted with, for example, phosgene to form the oxazolidinone ring. Such reactions and the preparation of the initial materials within the experience of the ordinary chemist with reference to the documents cited above describe analogous reactions and preparations. The epoxides of the formula CH2 (O) CH-CH20-HET can be prepared from the corresponding compound CH2 = CH-CH2-0-HET. Certain intermediate epoxide and alkane are novel and are provided as a further feature of the invention. The asymmetric epoxidation can be used to give the desired optical isomer. (f) When X is -SO- or -S02- the oxidation of a compound wherein X is -S- can be achieved by oxidation with standard reagents known in the art for the oxidation of a thio group to a sulfinyl or sulfonyl group . For example, a thio group can be oxidized in a sulfinyl group with a peracid such as m-chloroperoxybenzoic acid and oxidation agents such as potassium permanganate which can be used to convert a thio group to a sulfonyl group. (g) A compound of the formula (III) is reacted with a compound of the formula (IV) using conditions similar to those for the reaction of a compound of the formula (III) with a compound of the formula (V) described in the above. If no preparation of suitable starting materials is commercially available, of the formulas (III) and (IV) is as described above, or using the analogous process. The removal of any protecting groups, the formation of a pharmaceutically acceptable salt and / or the formation of a hydrolysable ester in vivo are within the skill of an ordinary organic chemist using standard techniques. In addition, details in these steps, for example the preparation of hydrolysable ester prodrugs in vivo, have been provided in the previous section in such esters, and in certain of the following non-limiting examples.

When an optically active form of a compound of the formula (I) is required, it can be obtained by carrying out one of the above procedures using an optically active starting material (formed, for example, by asymmetric induction or a suitable reaction step) , or by resolution of a racemic form of the compound or intermediate using a standard procedure, or by chromatographic separation of diastereoisomers (when they are produced). Enzymatic techniques may also be useful for the preparation of optically active compounds and / or intermediates. Similarly, when a pure regioisomer of a compound of the formula (I) is required, it can be obtained by carrying out one of the above procedures using a pure regioisomer as an initial material or by resolution of a mixture of regioisomers or intermediates using a process standard. According to a further feature of the invention there is provided a compound of the formula (I), or a pharmaceutically acceptable salt, or in vivo hydrolysable ester thereof for use in a method of treatment of the animal or human body by therapy. According to a further feature of the present invention there is provided a method for producing an antibacterial effect in a warm-blooded animal, such as a man in need of such treatment, comprising administering to the animal an effective amount of a compound of the present invention. invention, or a pharmaceutically acceptable salt, or an in vivo hydrolysable ester thereof. The invention also provides a compound of the formula (I) or a pharmaceutically acceptable salt, or an in vivo hydrolysable ester thereof, for use as a medicament and the use of a compound of the formula (I) of the present invention, or a pharmaceutically acceptable salt or in vivo hydrolysable ester thereof, in the manufacture of a medicament for use in the production of an antibacterial effect in a warm-blooded animal, such as a man. To use a compound of the formula (I), an in vivo hydrolysable ester or a pharmaceutically acceptable salt thereof, including a pharmaceutically salt of a hydrolysable ester in vivo, (hereinafter referred to in the pharmaceutical composition. a compound of this invention ") for the therapeutic treatment (including prophylactics) of mammals including humans, in particular in the treated infection, is normally formulated in accordance with standard pharmaceutical practice as a pharmaceutical composition. Therefore in another aspect of the present invention there is provided a pharmaceutical composition comprising a compound of the formula (I), hydrolysable in vivo or a pharmaceutically acceptable salt thereof, including a pharmaceutically acceptable salt of a hydrolysable ester in vivo, and a pharmaceutically acceptable diluent or carrier. The pharmaceutical compositions of this invention can be administered in standard form for the disease condition to be treated, for example, by oral rectal or parenteral administration. For these purposes the compounds of this invention can be formulated by means known in the art in the form of, for example, tablets, capsules, aqueous or oily solutions or suspensions, emulsions (lipids), dispersible powders, suppositories, ointments, creams, aerosols (or sprinklers), drops and sterile injectable aqueous or oily solutions or suspensions. In addition to the compounds of the present invention the pharmaceutical composition of this invention can also contain or be co-administered (simultaneously, sequentially or separately) with one or more known drugs selected from other clinically useful antibacterial agents (e.g., β-lactams or aminoglycosides) ) and / or other anti-infective agents (for example an antifungal triazole or amphotericin). This may include carbapenems, for example meropenem or imipenem, to expand the therapeutic effectiveness. The compounds of this invention may also contain or be co-adminisd with products of increased permeability / baccidal permeability proteins or spill pump inhibitors (BPIs) to improve the activity against the gram-negative baca resistant to bacal antibacal agents. A suitable pharmaceutical composition of this invention is suitable for oral administration in unit dose form, for example a tablet or capsule containing between 1 mg and 1 g of a compound of this invention, preferably between 100 mg and 1 g. of a compound. Especially preferred is a tablet or capsule containing between 50 mg and 800 mg of a compound of this invention, particularly in the range of 100 mg to 500 mg. In another aspect a pharmaceutical composition of the invention is suitable for intravenous, subcutaneous, or intramuscular injection, for example an injection containing between 0.1% w / v and 50% w / v (between lmg / ml and 500 mg / ml) of a compound of this invention. Each patient can receive, for example, a daily intravenous, subcutaneous or intramuscular dose of 0.5 mgkg "1 to 20 mgkg-1 to 20 mgkg-1 of a compound of this invention, the composition is adminisd 1 to 5 times per day. A daily dose of 5 mgkg-1 to 20 mgkg-1 of the compound of this invention is adminisd.Intravenous, subcutaneous and intramuscular dose can be given by means of a ball injection.Alatively the intravenous dose can be given by continuous infusion for a period of time Alatively, each patient may receive a daily oral dose which may be approximately equivalent to the daily parenl dose, the composition being adminisd 1 to 4 times per day A pharmaceutical composition to be intravenously dosed advantageously contain (for example in increased stability) a suitable baccidal, antioxidant or reducing agent, or a suitable sequesng agent, In other characstics of pharmaceutical compositions, process, method, use and manufacture of prior medicaments, the alative and preferred embodiments of the compounds of the invention described herein are also applied. Antibacal Activity: The pharmaceutically acceptable compounds of the present invention are useful antibacal agents because they have a good spectrum of activity in vivo against gram standard positive organisms, which are useful for screening, by activity against pathogenic baca. Notably, the pharmaceutically acceptable compounds of the present invention show activity against encocci, pneumococci and strains resistant to methicillin from S. aureus and coagulase negative staphylococcus. The antibacal spectrum and the potency of a particular compound can be deined in a standard test system. The (antibacal) properties of the compounds of the invention can be demonstrated and evaluated in vivo in conventional tests, for example by oral or intravenous dose of a compound to a warm-blooded mammal using standard techniques. The following results were obtained in a standard in vitro test system. The activity is described in s of the minimum inhibitory concentration (MIC) deined by the agar-sweet technique with a vaccine dimension of 104 CFU / point. Typically, the compounds are active in the range of 0.01 to 256 μg / ml. Staphylococcus was tested on agar, using a 104 CFU / dot vaccine and an incubation temperature of 37 ° C during standard 24-hour test conditions for the expression of methicillin resistance. Streptococcus and encoccus were tested on agar supplemented with 5% defibrinated horse blood, a 104 CFU / dot vaccine and an incubation temperature of 37 ° C in a 5% carbon dioxide atmosphere for 48 hours - the blood it was required for the growth of some of the test organisms.

MIC organism (μm / ml, Example 6 Staphylococcus eureus: Oxford 0.5 Novb Res 2.0 MRQR 1.0 Coagulase tive staphylococcus MS 0.5 MR 1.0 Streptococcus pyogenic C203 2.0 Enterococcus faecalis 2.0 Bacillus subtilis 0.5 Novb Res = Novobiocin retention MRQR = quinolone-resistant methicillin resistant MR = methicillin-resistant MS = sensitive methicillin The invention is now illustrated but not limited by the following examples in which unless stated otherwise: i) Evaporation is carried out by rotary evaporation in vacuo and carry out the work procedures after the removal of residual solids by filtration. (ii) the operations are carried out at room temperature, ie typically in the range of 18-26 ° C and in air unless otherwise stated, or at least the person skilled in another way or unless the expert person must otherwise work under an inert atmosphere; (iii) column chromatography (by the instantaneous procedure) was used to purify compounds and was performed on Merck Kieselgel silica (Art 9385) unless stated otherwise; (iv) the returns were given for illustration only and are not necessarily the maximum feasible; (v) the structure of the terminal products of the formula (I) are generally confirmed by NMR and the mass spectral techniques [proton magnetic resonance spectrum was generally determined in DMS0-D6 unless otherwise stated, using an operation of the Varian Gemini 2000 spectrometer at a field strength of 300 MHz, or a Bruker AM250 spectrometer operating at a field strength of 250 MHz; chemical changes were reported in parts per million below the tetramethylsilane field as a standard and internal multiplicities (d scale) and peak are shown in this way s, singlet; d doublet; AB or dd doublet of doublets; t, triplet; m, multiplet; Fast atom bombardment (FAB) mass spectrum data are generally obtained using a Platform spectrometer (supplied by Micromass) running in electrospray and, where appropriate, either positive or tive ion data were collected]; (vi) the intermediates are not generally and completely characterized and the purity was in general evaluation by thin-layer chromatography, infra-red (IR), spectral mass (MS) or NMR analysis; and (vii) in which the following abbreviations may be used: ® is a trademark; DMF is N, N-dimethylfomamide; DMA is N, N-dimethylacetamide; TLC is thin layer chromatography; HPLC is high pressure liquid chromatography; MPLC is medium pressure liquid chromatography; 'DMSO is dimethylsulfoxide; CDC13 deuterated chloroform; MS mass spectroscopy; ESP is electroaspersion; THF is tetrahydrofuran; TFA is trifluoroacetic acid; NMP is N-methylpyrrolidone; HOBT is 1-hydroxy-benzotrial; EtOAc is ethyl acetate; MeOH is methanol foforyl is (HO) 2-P (0) -0-; phosphoryl is (H0) 2-P-0-; EDC is 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide (hydrochloride); PTSA is paratoluenesulfonic acid.

Reference Example 1: 5 (R) -Hydroxymethyl-3- (4- (4- (5-cyanopyrid-2-yl) piperazin-1-yl) -3-luo-phenyl) -oxazolidin-2-one. (R) -Hydroxymethyl-3- (3-fluoro-4- (4-t-butoxycarbonylpiperazin-1-yl) phenyl) -oxazolidin-2-one (International Patent Application Publication WO 93/23384, 43.1 g, 0.11 M) stirring in ethanol (1000 ml) under nitrogen. A solution of ethanol of hydrogen chloride (3.8 M, 400 ml) was added slowly, and the mixture was stirred at room temperature for 18 hours. The resulting precipitate was filtered, washed with diethyl ether (3 x 250 ml), and dried, to give 5 (R) -hydroxymethyl-3- (3-fluoro-4- (piperazin-1-yl) phenyl hydrochloride) oxazolidin-2-one. An additional culture was obtained by evaporation of the mother liquors to give a total yield of 38.7 g. XH NMR (300 MHz. DMS0-D6) d: 3.17 (m, 8H); 3.53 (dd, 1H); 3.64 (dd, 1H); 3.79 (dd, 1H); 4.03 (t, 1H); 4.66 (m, 1H); 7.10 (t, 1H); 7.21 (dd, 1H); 7.52 (dd, 1H); 9.39 (br s, 2H). MS (ESP): 296 (MH +) for C? H? 8FN303. The hydrochloride of 5 (R) -hydroxymethyl-3- (3-fluoro-4- (piperazin-1-yl) phenyl) oxazolidin-2-one (25 g, 75.4 mm) was suspended by stirring in acetonitrile (700 ml) under nitrogen, and triethylamine (16.8 g, 166 mM) was added. The mixture was stirred for 10 minutes and then 2-chloro-5-cyanopyridine (10.3 g, 75.4 mmol) was added, and the mixture was heated under reflux for 18 hours. After cooling, the resulting solid was filtered, washed with water (3 x 500 ml) diethylether (2 x 500 ml) to give 5 (R) -hydroxymethyl-3- (4- (4- (5-cyanopyrid-2) -yl) piperazin-1-yl) -3-fluorophenyl) -oxazolidin-2-one. An additional culture was obtained by evaporation of the mother liquors to give a total yield of 23.2 g. MS (ESP): 398 (MH +) for C20H20FN5O3. XH NMR (300 MHz DMS-D6) d: 3.03 (t, 4H); 3.54 (m, 1H); 3.63 (m, 1H), 3.78 (t overlapping m, 5H), 4.03 (t, 1H), 4.66 (m, 1H), 5.18 (t, 1H), 6.97 (d, 1H), 7.07 (t, 1H), 7.20 (dd, 1H), 7.53 (dd, 1H), 7.85 (dd, 1H), 8.49 (d, 1H), Example 1: 5 (R) Pyrid-2-yloxymethyl-3- (4- (4- (5-cyanopyrid-2-yl) piperazin-1-yl) -3-fluorophenyl) oxazolidin-2-one 5 (R) -Hydroxymethyl-3- (4- (4- (5-cyanopyrid-2-) was suspended il) piperazin-1-yl) -3-fluorophenyl) -oxazolidin-2-one (397 mg, 1 mM), 2-hydroxypyridine (104 mg, 1.1 mM) and triphenylphosphine-bonded polymer (3 mM / g, 416 mg 1.25 M), with stirring in dry tetrahydrofuran (10 ml), Diisopropylazodicarboxylate (242 mg, 1.2 mM) was added dropwise by syringe, and the mixture was stirred at room temperature for 1 hour. Evaporated to dryness, dissolved in ethyl acetate, and applied to a Mega Bond Elut® column of silica 10 g, eluting with a mixture of ethyl acetate and isohexane (1: 1) .The relevant fractions were combined and evolved. they were quenched to give the title compound (45 mg). MS (ESP); 475 (MH +) for C25H23FN603 XH NMR (300 MHz, DMSO-D6) d: 3.03 (t, 4H); 3.81 (t, 4H); 3.89 (dd, 1H); 4.17 (t, 1H); 4.47 (dd, 1H); 4.55 (dd, 1H); 5.03 (m, 1H); 6.82 (d, 1H); 6.99 (t overlapping dd, 2H); 7.08 (t, 1H); 7.21 (dd, 1H); 7.52 (dd, 1H); 7.70 (td, 1H); 7.85 (dd, 1H); 8.15 (dd, 1H); 8.48 (d, 1H). Example 2: 5 (R) - (6-Chloropyridazin-3-yloxymethyl) -3- (4- (4- (5-eiapyrid-2-yl) piperazin-1-yl) -3-f-luo-phenyl) -oxazolidin-2 -one; Example 3: 5 (R) -Pirazin-2-yloxymethyl-3- (4- (4- (5-cyanopyrid-2-yl) piperazin-1-yl) -3-fluorophenyl) oxazolidin-2-one; 5 (R) -Hydroxymethyl-3- (4- (4- (5-cyanopyrid-2-yl) piperazin-1-yl) -3-fluorophenyl-oxazolidin-2-one (240 mg, 0.6 mM) was added, in portions to a stirred suspension of sodium hydride (60% in oil, 26 mg, 0.65 mM) in dry N, N-dimethylformamide under nitrogen.The mixture was stirred at room temperature for 25 minutes, the appropriate chlorheterocycle was added (0.6 mm), and stirring was continued for 18 hours.The mixture was diluted with water (20 ml), and the resulting precipitate was filtered, washed with diethyl ether, and dried to give the title compounds.

Notes 1: XH NMR (300 MHz, DMSO) -d: 3.03 (t, 4H); 3.79 (t, 4H); 3.92 (dd, 1H); 4.18 (t, 1H); 4.65 (dd, 1H); 4.72 (dd, 1H); 5.09 (m, 1H); 6.97 (d, 1H); 7.08 (t, 1H); 7.21 (dd, 1H); 7.38 (d, 1 HOUR); 7.52 (dd, 1H); 7.80 (d, 1H); 7. 6 (dd, 1H); 8.48 (d, 1 HOUR) . MS: ESP + (M + H) = 510 for C24H2? ClFN703. Notes 2: XH-NMR (300 MHz, DMSO): d: 3.03 (t, 4H); 3.79 (t, 4H); 3.91 (dd, 1H); 4.18 (t, 1H); 4.53 (dd, 1H); 4.60 (dd, 1H); 5.08 (m, 1H); 6.98 (d, 1H); 7.08 (t, 1H); 7.22 (dd, 1H); 7.52 (dd, 1 HOUR. 7.86 (dd, 1H); 8.23 (overlapping m, 2H); 8.34 1H); 8. 50 (d, 1H). MS: ESP + (M + H) = 476 for C24H22FN703. Example 4: 5 (R) -Pyrimidin-4-yloxymethyl-3- (4- (4- (5-cyanopyrid-2-yl) piperazin-1-yl) -3-f-luoro-enyl) -oxazolidin-2-one suspended 5 (R) -Hydroxymethyl-3- (4- (4- (5-cyanopyrid-2-yl) piperazin-1-yl) -3-fluorophenyl) oxazolidin-2-one (397 mg, 1 mM), 4-hydroxypyrimidine (106 mg, 1.1 mM) and triphenylphosphine (327 mg, 1.25 mM), with stirring in dry tetrahydrofuran (10 ml). Diisopropylazodicarboxylate (242 mg, 1.2 mM) was added dropwise by syringe, and the mixture was stirred at room temperature for 30 minutes. The reaction mixture was evaporated to dryness, dissolved in ethyl acetate / isohexane (3: 1), and applied to a silica Mega Bond Elut® column 20 g, eluting with an increased polarity gradient of 3: 1 acetate of ethyl in isohexane to pure ethyl acetate. The relevant fractions were combined and evaporated to give the title compound (240 mg). MS (ESP): 476 (MH +) for C 24 H 22 FN 703. XH-NMR (300 MHz, DMSO): d: 3.03 (t, 4H); 3.79 (t, 4H); 3.89 (dd, 1H); 4.17 (t, 1H); 4.56 (dd, 1H); 4.61 (dd, 1H); 5.06 (m, 1H); 6.96 (overlapping m, 2H); 7.08 (t, 1H); 7.20 (dd, 1H); 7.51 (dd, 1H); 7.86 (dd, 1H); 8.50 (d, 1H); 8.50 (d, 1H); 8.79 (s, 1H). Example 5: 5 (R) -Pyridazin-3-yloxymethyl-3- (4- (4- (5-cyanopyrid-2-yl) piperazin-1-yl) -3-fluoro-enyl) oxazolidin-2-one Was dissolved 5 (R) - (6-Chloropyridazin-3-yloxymethyl) -3- (4- (4- (5-cyanopyrid-2-yl) piperazin-1-yl) -3-fluorophenyl) -oxazolidin-2-one ( 176 mg, 0.35 mM) in N, N-dimethylformamide (20 ml) and triethylamine (71 mg, 0.7 mM) and palladium on charcoal (5%, 30 mg) was added with stirring. The atmosphere in the vessel was replaced with hydrogen under a balloon, and the mixture was stirred 18 hours at room temperature. The catalyst was filtered through celite, the solvent was evaporated, and the residue was dissolved in dichloromethane, and applied to a Mega Bond Elut column of silica 20 g, eluting with an increased polarity gradient of pure dichloromethane to 19: 1 dichloromethane in methanol. The relevant fractions were combined and evaporated to give the title compound (22 mg). MS (ES): 476 (MH +) for C 24 H 22 FN 7? 3 NMR (DMSO-D 6) d: 3.04 (t, 4H); 3.81 (t, 4H); 3.94 (dd, 1H); 4.19 (t, 1H); 4.70 (overlapping m, 2H); 5.11 (m, 1H); 6.99 (d, 1H); 7.09 (t, 1H); 7.23 (overlapping m, 2H); 7.53 (dd, 1H); 7.61 (m, 1H); 7.86 (dd, 1H); 8.50 (d, 1H); 8.91 (dd, 1H). Example 6 (R) -Pyrid-2-yloxymethyl-3- (3-fluoro-4- (3,6-dihydro- (2H) -pyran-4-yl) enyl) oxazolindin-2-one 2- was added Hydroxypyridine (108 mg, 1.14 mmol) per portion, at room temperature, to a stirred suspension of sodium hydride (48 mg, 1.2 mmol of a 60% dispersion in oil) in DMF (5 mL) under a nitrogen atmosphere. The mixture was stirred for 30 minutes then 5 (R) methylsulfonyloxymethyl-3- (3-fluoro-4- (3,6-dihydro- (2H) -pyran-4-yl) phenyl) oxazolidin-2-one ( International Patent Application Publication W097 / 09328, 400 mg, 1.08 mmol) in one range. The reaction was stirred and heated at 60 ° C for 5 hours, then quenched in water and extracted with ethyl acetate. The extract was washed twice with water and once with saturated brine, dried over magnesium sulfate and evaporated to give an oil. The oil was purified by flash chromatography (silica Merck 9385, 2.5% methanol / dichloromethane eluent) to give the title product (60 mg, 15%) as a crystalline solid. MS ESP + (M + H) + = 371. XH-NMR (300 MHz, CDCl 3): d = 2.50 (m, 2H), 3.94 (t, 2H), 3.98 (dd, 1H), 4.15 (t, 1H), 4.34 (m, 2H), 4.60 (d , 2H), 5.05 (m, 1H), 6.04 (m, 1H), 6.77 (d, 1H), 6.92 (dd, 1H), 7.26 (m, 2H), 7.42 (dd, 1H), 7.60 (m, 1H), 8.14 (dd, 1H). Example 7: 5 (R) - (4-Methylpyrid-2-yloxymethyl) -3- (3-fluoro-4- (3,6-dihydro- (2H) -pyran-4-yl) phenyl) oxazolidin-2- ona Diisopropylazodicarboxylate (290 mg, 1.43 mmol) was added dropwise at room temperature to a stirred solution of 5 (R) -hydroxymethyl-3- (3-fluoro-4- (3,6-dihydro- (2H) - pyran-4-yl) phenyl) oxazolidin-2-one (International Patent Application Publication WO 97/09328, 300 mg, 1.02 mmol), 2-hydroxy-4-methylpyridine (167 mg, 1.53 mmol) and triphenylphosphine (402 mg, 1.53 mmol) in THF (8 ml). The resulting solution was stirred at room temperature for 30 minutes before evaporating the solvent to give an oil. The oil was purified by flash chromatography (silica Merck 9385, ethyl acetate / isohexane (3: 2) eluent) to give the title product (181 mg, 46%) as a crystalline solid. 1 H-NMR (300 MHz, CDC13): d = 2.52 (m, 2H), 3.92 (t, 2H), 3.97 (dd, 1H), 4.12 (t, 1H), 4.32 (m, 2H), 4.59 (d , 2H), 5.02 (m, 1H), 6.06 (m, 1H), 6.59 (s, 1H), 6.75 (d, 1H), 7.26 (m, 2H), 7.41 (dd, 1H), 7.99 (d, 1 HOUR) . MS ESP + (M + H) + = 385. Example 8: 5 (R) - (3-Methylpyrid-2-yloxymethyl) -3- (3-fluoro-4- (3,6-dihydro- (2H) -piran -4-yl) enyl-oxazolidin-2-one The title product was prepared by the general method of Example 2, using the same initial oxazolidinone material as in Example 7 (300 mg, 1.02 mmol), sodium hydride ( 95 mg, 2.37 mmol of a dispersion in 60% oil) and 2-fluoro-3-methylpyridine (130 mg, 1.17 mmol) in DMF (3 ml) The resulting reaction product was purified by flash chromatography (silica Merck 9385 ethyl acetate / isohexane (7: 3) eluent) to give the title product (50 mg, 13%) as a crystalline solid MS ESP + (M + H) + = 385. 1 H-NMR 9300 MHz, CDCl 3) : d = 2.12 (s, 3H), 2.51 (m, 2H), 3.92 (t, 2H), Y.99 (dd, 1H), 4.17 (t, 1H), 4.32 (m, 2H), 4.61 (m , 2H), 5.05 (m, 1H), 6.07 (m, 1H), 6.84 (dd, 1H), 7.27 (m, 2H), 7.35-7.44 (m, 2H), 7.06 (d, 1H). 1Q2 Example 9: 5 (R) - (6-Chloropyridazin-3-yloxymethyl) -3- (3-fluoro-4- (3,6-dihydro- (2H) -pyran-4-yl) phenyl) oxazolidin-2- The product of the title was prepared by the general method of Example 8 using the same starting material of oxazolidinone (600 mg, 2.05 mmol), sodium hydride (90 mg, 2.25 mmol of a dispersion in 60% oil) and 3, 6-dichloropyridazine (350 mg, 2.35 mmol) in DMF (6 ml). The mixture was stirred at room temperature for 18 hours then at 60 ° C for 6 hours, and the resulting product was purified by flash chromatography (silica Merck 9385, ethyl acetate / isohexane (7: 3) eluent) to give the product of the product. title (178 mg, 21%) as a crystalline solid. MS: ESP + (M + H) + = 406/408. ^ -NMR (300 MHz, CDC13): d = 2.52 (m, 2H), 3.86-4.00 (m, 3H), 4.22 (m, 1H), 4.32 (m, 2H), 4.70-4.90 (m, 2H) , 5.10 (m, 1H), 6.06 (m, 1H), 7.06 (dd, 2H), 7.18-7.33 (m, 2H), 7.44 (m, 2H). Example 10: 5 (R) -Pyridazin-3-yloxymethyl-3- (3-fluoro-4- (3,6-dihydro- (2H) -pyran-4-yl) phenyl) oxazolidin-2-one was added. % palladium on carbon (20 mg) to a stirred suspension of Example 9 (240 mg, 0.59 mmol) and ammonium formate (112 mg, 1.78 mmol) in ethanol (10 ml) under a nitrogen atmosphere. The reaction was stirred at room temperature for 4 hours, then filtered through celite. The filtrate was evaporated under reduced pressure to give a gum which was extracted into methanol (20 ml) and stirred with sodium carbonate (500 mg) for 30 minutes. The mixture was then filtered and the filtrate was evaporated to give a gum, which was purified by flash chromatography (silica Merck 9385, 3% methanol / dichloromethane eluent) to give the title product (91 mg, 41%) as a solid. crystalline. 1H-NMR (300MHz, CDC13): d = 2.52 (m, 2H), 3.92 (t, 2H), 3.97 (dd, 1H), 4.20 (t, 1H), 4.31 (m, 2H), 4.79 (dd, 1H), 4.88 (dd, 1H), '5.10 (m, 1H), 6.06 (m, 1H), 7.05 (d, 1H), 7.28 (m, 2H), 7.42 (m, 2H), 8.90 (d, 1 HOUR) . MS: ESP + (M + H) + = 372. Example 11: 5 (R) -Pyrimidin-4-yloxymethyl-3- (3-fluoro-4 (3,6-dihydro- (2H) -pyran-4-yl) phenyl) oxazolidin-2-one The title product was prepared by the general method of Example 7, using the same starting material of oxazolidinone (300 mg, 1.02 mmol), 4-hydroxypyrimidine (147 mg, 1.53 mmol), diisopropylazodicarboxylate (289 mg, 1.43 mmol) and triphenylphosphine (402 mg, 1.53 mmole) in THF (8 ml). The resulting reaction product was purified by flash chromatography (silica Merck 9385, 2.5% methanol / dichloromethane eluent) to give the title product (186 mg, 49%) as a crystalline solid. XH-NMR (300 MHz, CDCl 3): d = 2.50 (m, 2H), 3.91-3.98 (m, 3H), 4.17 (t, 1H), 4.32 (m, 2H), 4.64 (dd, 1H), 4.72. (dd, 1H), 5.04 (m, 1H), 6.06 (m, 1H), 6.79 (d, 1H), 7.28 (m, 2H), 7.42 (dd, 1H), 8.49 (d, 1H), 8.78 ( s, 1H). MS: ESP + (M + H) + = 372.

Example 12: 5 (R) -Pirazin-2-yloxymethyl-3- (3-fluoro-4- (3,6-dihydro- (2H) -pyran-4-yl) phenyl) oxazolidin-2-one The product of the title was prepared by the general method of Example 8 using the same starting material of oxazolidinone (300 mg, 1.02 mmol), sodium hydride (45 mg, 1.12 mmol of a dispersion in 60% oil) and 2-chloropyrazine (130 mg , 1.13 mmol) in DMF (3 ml). The resulting reaction product was purified by flash chromatography (silica Merck 9385, 2.5% methanol / dichloromethane eluent) to give the title product (171 mg, 45%) as a crystalline solid. 1H-NMR (300MHz, CDC13): d = 2.51 (m, 2H), 3.92 (t, 2H), 3.97 (dd, 1H), 4.08 (t, 1H), 4.32 (m, 2H), 4.62 (m, 2H), 5.08 (m, 1H), 6.06 (m, 1H), 7.28 (m, 2H), 7.43 (dd, 1H), 8.10 (t, 1H), 8.21 (d, 1H), 8.29 (d, 1H) ). MSj_ ESP + (M + H) + = 372. Example 13: 5 (R) - (5-Chloropyridin-2-yloxymethyl) -3- (3-fluoro-4- (3,6-dihydro- (2H) -pyran-4-yl) phenyl) oxazolidin-2- The product of the title was prepared by the general method of Example 7 using the same starting material of oxazolidinone (300 mg, 1.02 mmol), 3-chloro-6-hydroxypyridine (146 mg, 1.13 mmol), diisopropylazodicarboxylate (227 mg, 1.12 mmol). mmoles) and triphenylphosphine (305 mg, 1.16 mmol) in THF (5 ml). The resulting reaction product was purified by flash chromatography (silica Merck 9385, ethyl acetate / isohexane (3: 2) eluent) to give the title product (197 mg, 48%) as a crystalline solid. 1H-NMR (300 MHz, CDC13): d = 2.51 (m, 2H), 3.90-4.00 (m, 3H), 4.14 (t, 1H), 4.30 (m, 2H), 4.56 (m, 2H), 5.02 (m, 1H), 6.05 (m, 1H), 6.74 (d, 1H), 7.20-7.30 (m, 2H), 7.40 (d, 1H), 7.55 (dd, 1H), 8.10 (d, 1H). MS_ ESP + (M + H) + = 405/407. Example 14: 5 (R) -Pyrid-2-yloxymethyl-3- (4-acetylphenyl) -oxazolidin-2-one 5 (R) -Hydroxymethyl-3- (4-acetylphenyl) -oxazolidin- was added in portions 2-one (CLJ Wang et al, Tetrahedron, Vol.45, 1323, (1989), 300mg, 1.28 mmol), at room temperature, to a stirred suspension of sodium hydride (56 mg, 1.4 mmol of a dispersion in oil 60%) in DMF (3 ml) under a nitrogen atmosphere.The mixture was stirred for an additional 15 minutes then 2-fluoropyridine (148 mg, 1.53 mmol) was added.The reaction was stirred for 18 h before it was extinguished The extract was washed with water (3x) and saturated brine (lx), then evaporated to give an orange gum, purified by flash chromatography (silica Merck 9385, ethyl acetate / isohexane (7). : 3)) to give the title compound (27mg, 7%) as a colorless crystalline solid MS: ESP + (M + H) + = 313.

XH-NMR (300MHz, CDC13): d = 2.60 (s, 3H), 4.07 (dd, 1H), 4.22 (t, 1H), 4.62 (d, 2H), 5.08 (m, 1H), 6.77 (d, 1H), 6.93 (dd, 1H), 7.59 (m, 1H), 7.68 (d, 2H), 7.99 (d, 2H), 8.14 (d, 1H). Example 15: 5 (R) -Pyrid-2-yloxymethyl-3- (4- (4-bromoimidazol-1-yl) -3-fluorophenyl) -oxazolidin-2-one Prepared by the general method of Example 7 using (R) -Hydroxymethyl-3- (4- (4-bromoimidazol-1-yl) -3-fluoro) phenyl) oxazolidin-2-one (W097 / 31917; 300 mg, 0.84 mmol), 2-hydroxypyridine (96 mg, 1.01 mmol), diisopropylazodicarboxylate (204 mg, 1012 mmol) and triphenylphosphine (270 mg, 1.03 mmol) in THF (5 mL). It was purified by flash chromatography (silica Merck 9385, 2. 5% methanol / dichloromethane) to give the title compound (156 mg, 43%) as a colorless crystalline solid. XH NMR (300 MHz, CDC13): d = 4.06 (dd, 1H), 4.18 (t, lH), 4.62 (d, 2H), 5.10 (m, 1H), 6.78 (d, 1H), 6.94 (m, 1H), 7.20 (d, 1H), 7.37 (m, 2H), 7.55-7.67 (m, 2H), 7.72 (d, 1H), 8.14 (d, 1 HOUR) . MS_ ESP + (M + H) + = 433/435. Example 16: 5 (R) -Pyrid-2-yloxymethyl-3- (4-methylthiophenyl) -oxazolidin-2-one Prepared by the general method of Example 7 using 5 (R) -hydroxymethyl-3- (4-methylthiophenyl) ) -oxazolidin-2'-one (prepared from the reaction of 4-methylthioaniline and (R) -glycidyl butyrate, 200 mg, 0.84 mmol), 2-hydroxypyridine (90 mg, 0.95 mmol), diisopropylazodicarboxylate (190 mg , 0.94 mmole) and triphenylphosphine (252 mg, 0.96 mmole) in THF (5 ml). Purified by flash chromatography (silica Merck 9385, ethyl acetate / isohexane (3: 2)) to give the title compound (123 mg, 46%) as a colorless crystalline solid. 1 H-NMR (300 MHz, CDC13): d = 2.49 (s, 3 H), 3.97 (dd, 1 H), 4.13 (t, 1 H), 4.60 (d, 2 H), 5.03 (m, 1 H), 6.77 (d , 1H), 6.92 (dd, 1H), 7.30 (d, 2H), 7.51 (d, 2H), 7.58 (m, 1H), 8.13 (d, 1H).

MS: ESP + (M + H) + = 317. Example 17 5 (R) -Pyrid-3-yloxymethyl-3- (3-f luoro-4- (3,6-dihydro- (2H) -piran-4- il) phenyl) oxazolidin-2-one Prepared by the general method of Example 6 using the same starting material, (400 mg, 1.08 mmol), sodium hydride (48 mg, 1.2 mmol of a 60% dispersion) and -hydroxypyridine (108 mg, 1.14 mmol) in DMF (5 ml). Purified by flash chromatography (silica Merck 9385, 3% methanol / dichloromethane) to give the title compound (231 mg, 58%) as a colorless solid. 1H NMR (300 MHz, CDC13): d = 2.50 (m, 2H), 3.92 (t, 2H), 4.08 (dd, 1H), _4.21 (t, 1H), 4.26-4.34 (m, 4H), 5.03 (m, 1H), 6.06 (m, 1H), 7.20-7.34 (m, 4H), 7.44 (d, 1H), 8.30 (m, 1H), 8.34 (m, 1H). MS _ ESP + (M + H) + = 371. No Example 18. Example 19: 5 (R) - (6-Methylpyrid-2-yloxymethyl) -3- (3-fluoro-4- (3,6-dihydro) - (2H) -pyran-4-yl) phenyl) oxazolidin-2-one The same starting material (300 mg, 1.02 mmol), 2-hydroxy-6-methylpiperidine (167 mg) was prepared by the general method of Example 7. 1.53 mmole) diisopropylazodicarboxylate (290 mg, 1.43 mmol) and triphenylphosphine (402 mg, 1.53 mmol) in THF (8 ml). Purified by flash chromatography (silica Merck 9385, 40%, ethyl acetate / isohexane) to give the title compound (197 mg, 50%) as a crystalline solid. MS: ESP + (M + H) + = 385. XH-NMR (300 MHz, CDC13): d = 2.44 (s, 3H), 2.50 (m, 2H), 3.91 (t, 2H), 4.00 (dd, 1H), 4.12 (t, 1H), 4.31 (m, 2H), 4.52-4.67 (m, 2H), 5.03 (m, 1H), 6.05 (m, 1H), 6.54 (d, 2H), 6.74 (d, 2H), 7.21-7.32 (m, 2H), 7.42 (d, 1H), 7.48 (t, 1H). Example 20: 5 (R) - (Pyrid-4-yloxymethyl) -3- (3-fluoro-4- (3,6-dihydro- (2H) -pyran-4-yl) enyl) oxazolidin-2-one prepared by the general method of Example 19 using the same starting material (300 mg, 1.02 mmol), 4-hydroxypyridine (107 mg, 1.13 mmol), diisopropylazodicarboxylate (227 mg, 1.12 mmol) and triphenylphosphine (305 mg, 1.16 mmol) in THF (5 ml). Purified by flash chromatography (silica Merck 9385, 5% methanol / dichloromethane to give the title compound (150 mg, 40%) as a crystalline solid. X H-NMR (300 MHz, CDCl 3): d = 2.51 (m, 2 H), 3.92 (t, 2 H), 4.04 (dd, 1H), 4.21 (t, 1H), 4.26-4.35 (m, 4H), 5.02 (m, 1H), 6.07 (m, 1H), 6. 83 (d, 2H), 7. 22-7. 32 (m, 2H), 7. 42 (d, 1H), 8. £ 4 (d, 2H). MS: ESP + (M + H) + = 371. Example 21: (5R) -Pirazin-2-yloxymethyl-3- (4- (4- (6-cyano-pyridazin-3-yl) piperazin-1-yl) -3-f-luo-phenyl) -oxazolidin-2-one The method of Examples 2 and 3 was essentially used starting from 3- (4- (4- (6-cyano-pyridazin-3-yl) piperazin-1-yl) -3-fluorophenyl) -5- ( R) -hydroxymethyloxazolidin-2-one (prepared by analogy to Reference Example 1; 240 mg, 0.6 mM) and 2-chloropyrazine (68.7 mg, 0.6 mM). The unpurified material was precipitated and purified by chromatography on a Mega Bond Elut® silica column 20 g, eluting in a gradient increased in polarity from 0 to 2.5% methanol in dichloromethane. The relevant fractions were combined and evaporated to give the title compound (151 mg). MS (ESP): 477 (MH +) for C23H2? FN803 NMR (DMSO-d6) d: 3.08 (t, 4H); 3.90 (t overlapping m, 5H) 4.18 (t, 1H); 4.53 (dd, 1H); 4.61 (dd, 1H); 5.08 (m, 1H) 7.11 (t, 1H); 7.23 (dd, 1H); 7.40 (d, 1H); 7.53 (dd, 1H) 7.87 (d, 1H); 8.24 (overlapping m, 2H); 8.33 (s, 1H). Example 22: (5R) -Pyridin-2-yloxymethyl-3- (4- (4- (6-cyanopyridazin-3-yl) piperazin-1-yl) -3-fluorophenyl) oxazolidin-2-one Was used essentially the method of Example 21 starting from 3- (4- (4- (6-cyano-pyridazin-3-yl) piperazin-1-yl) -3-fluorophenyl) -5 (R) -hydroxymethyloxazole-dinitide. 2-one (240 mg, 0.6 mM) and 2-fluoropyridine (58.2 mg, 0.6 mM), to give the title compound (54 mg). MS (ESP): 476 (MH +) for C 24 H 22 FN 03 NMR (DMSO-dβ) d: 3.08 (t, 4H); 3.90 (t overlapping m, 5H); 4.16 (t, 1H); 4.47 (dd, 1H); 4.54 (dd, 1H); 5.04 (m, 1H); 6. 82 (d, 1H); 7.10 (t, 1H); 7.22 (t, 1H); 7.40 (d, 1H); 7.53 (dd, lH); # -_ 7.87 (d, 1H); 8.24 (overlapping m, 2H); 8.33 (s, 1 HOUR) . Example 23: (5R) - (6-Cyano-pyridazin-3-yl) oxymethyl-3- (4- (4- (6-cyano-pyridazin-3-yl) piperazin-1-yl) -3-fluorophenyl) oxazolidin -2-one The method of Example 21 was essentially used starting from 3- (4- (4- (6-cyanopyridazin-3-yl) piperazin-1-yl) -3-fluorophenyl) -5 (R) - hydroxymethyloxazoli-din-2-one (240 mg, 0.6 mM) and 3-chloro-cyanopyridazine (84 mg, 0. 7 mM), to give the title compound (60 mg). MS (ESP): 502 (MH +) for C 24 H 2 o FN 903 NMR (DMS0-d 6) d; 3.09 (t, 4H); 3.92 (t, 4H); 3.96 (dd, 1H); 4. 20 (t, 1H); 4.78 (dd, 1H); 4.85 (dd, 1H); 5.12 (m, 1H); 7.11 (t, 1H); 7.22 (dd, 1H); 7.40 (d, 1H); 7.53 (overlapping m, 2H); 7.88 (d, 1H); 8.24 (d, 1H). Example 24 The following illustrates pharmaceutically representative dosage forms containing a compound of the formula (I), an in vivo hydrolysable ester or a pharmaceutically acceptable salt thereof, which includes a pharmaceutically acceptable salt of a hydrolysable ester in vivo (hereinafter forward compound X), for therapeutic or prophylactic use in humans: (a) Tablet I mg / tablet Compound X 500 Lactose Ph.Eur 430 Croscarmellose sodium 40 Polyvinylpyrrolidone 20 - Magnesium stearate 10 (b) Tablet II mg / tablet Compound X 100 Lactose Ph.Eur 179 Croscarmellose sodium 12 - Polyvinylpyrrolidone 6 Magnesium stearate 3 (c) Tablet III mg / tablet Compound X 50 Lactose Ph.Eur 229 Croscarmellose sodium ... '12 Polyvinylpyrrolidone 6 Magnesium stearate 3 (d) ) Tablet IV mg / tablet Compound X 1 Lactose Ph.Eur 92 Croscarmellose sodium 4 Polyvinylpyrrolidone 2 Magnesium stearate 1 (e) Capsule mg / capsule Compound X 10 Lactose Ph.Eur 389 Croscarmellose sodium 100 Magnesium stearate 1 (f) Injection I Compound X 50% w / v Isotonic aqueous solution at 100% (g) Injection IX (ie bolus) Compound X 10% w / v Aqueous solution isotonic at 100% (h) Injection III Compound X 5% w / v Isotonic aqueous solution at 100% (i) Injection IV (ie infusion) Compound X 1% w / v Isotonic aqueous solution at 100% / Shock absorbers, pharmaceutically active acceptable, oils or cosolvents such as polyethylene glycol, polypropylene glycol, glycerol or ethanol, glidants (such as silicon dioxide) or complexing agents before such as a cyclodextrin (e.g., hydroxy-propyl-β-cyclodextrin or sulfo-butyl-ether β- cyclodextrin) can be used to help the formulation. Also, improvements in aqueous solubility, if desired, can be carried out, for example, by conjugation of a compound of the formula (I) with a phospholipid (such as a derivative (phospho) choline) to form a micellar emulsion. Note: The above formulations can be obtained by conventional procedures well known in the pharmaceutical art, for example as described in "Remington: The Science &Practice of Pharmacy" Vols. I & II (Ed. AR Gennaro (Chairman) et al; Publisher: Mack Publishing Company, Easton, Pennsylvania, 19th Edition - 1995) and "Pharmaceutics - The Science of Dosage Form 'Desing" (Ed. ME Aulton; Publisher: Churchill Livingstone; first publication 1988). Tablets (a) - (d) can be (polymer) covered by conventional means, for example providing an enteric coating of cellulose acetate phthalate.

Claims (13)

1. CLAIMS 1. A compound of formula (I), or a pharmaceutically acceptable salt, or an acceptable capable ester, or an in vivo hydrolysable ester thereof, s > wherein X is -O- or -S-; HET is a 6-membered C-linked heteroaryl ring containing 1 or 2 N, whose ring is optionally substituted at any available C atom (provided that when the N atom is adjacent to the X bond, there is no substitution at any of the C atoms which are adjacent to this atom N) by substituents 1, 2 or 3 independently selected from C? -4 alquilo ,alkyl, amino, C a-4-aakylamino, C alquilo-4 alquiloalkyl, C? _ alcoalkoxycarbonyl and halogen; Q is selected from Ql to Q9: Ql Q2 Q3 Q4 Q5 Q6 Q7 Q8 Q9 wherein R2 and R3 are independently hydrogen or fluoro; where Ai is carbon or nitrogen; Bi is 0 or S (or, in Q9 only, NH); X q is O, S or N-R 1 (wherein R 1 is hydrogen, C 4 alkyl or hydroxy C 1-4 alkyl); and where in Q7 each A is independently selected from carbon or nitrogen, with a maximum of 2 nitrogen heteroatoms in the 6-membered ring and Q7 is linked to T by any of the atoms Ai (where i is carbon) , and it is bonded in the 5 membered ring by means of the specified carbon atom, or by means of Ai when i is carbon; Q8 binds to T via either the carbon atoms specified in the 5-membered ring and bonded to the benzo ring by means of either the two specified carbon atoms on either side of the bond bonds shown; and Q9 is linked by means of either of the two specific carbon atoms on either side of the bond bond shown; wherein T is selected from the groups in (TA) to (ID) below (where AR1, AR2, AR2a, AR2b, AR3, AR3a, AR3b, AR4, AR4a, CY1 and CY2 are defined in the following); (TA) T is selected from the following groups: (TAa) ARl, ARl alkyl of C? _4, AR2 (attached carbon), AR3; (TAb) AR1-CH (OH), AR2-CH (0H), AR3-CH (0H) -; (TAc) Arl-CO, AR2-CO, AR3-CO, AR4-C0; (TAd) AR1-0-, AR2-0-, AR3-0 ,; (TAe) ARl S (0) q-, AR2-S (0) q-, AR3-S (0) q- (q is 0, 1 or 2) (TAf) an N-linked optionally substituted (completely unsaturated) 5-membered heteroaryl ring system containing 1, 2 or 3 nitrogen atoms; (TAg) a bound tropol-3-one or carbon-bound tropol-4-one, optionally substituted at a position not adjacent to the bonding position; or (TB) T is selected from the following groups: - (TBa) halo or C? _4 alkyl. { optionally substituted by one or more groups each independently selected from hydroxy, C 1-4 alkoxy, C 1-4 alkanoyl, cyano, halo, trifluoromethyl, C 1-4 alkoxycarbonyl, NRvRw, C 1-6 alkanoylamino, C 1-6 alkoxycarbonyloamino 4, N-C 1-4-N-alkanoylamino of Ci-g, alkyl of C? _4S (0) q- (q is 0, 1 or 2), CY1, CY2 or AR1}; (TBb) -NRv ^ w1; (TBc) ethenyl, 2-C2-4 alkyletenyl, 2-cyanoethenyl, 2-cyano-2- (C4-4 alkyl) ethenyl, 2-nitro tentenyl, 2-nitro-2- (C4-4 alkyl, ) ethenyl, 2- (C 1-4 alkylaminocarbonyl) ethenyl, 2- ((1-4-alkoxycarbonyl) ethenyl, 2- (AR 1) ethenyl, 2- (AR 2) ethenyl; (TBd) R 10 CO-, R 10 S ( 0) q- (q is 0, 1 or 2) or R10CS- where R10 is selected from the following groups: (TBda) CY1 or CY2;. {TBdb) hydrogen, C3-4 alkoxycarbonyl, trifluoromethyl, - NRvRw, ethenyl, 2- (C? -4, 2-cyanoethenyl, 2-cyano-2- (C alquilo _4) alkyl ethenyl, 2-nitro-tennyl, 2-nitro-2- (C alquilo-alkyl) ethenyl, 2- (C 1 -) alkylaminocarbonyl, 2- (C 1-4 alkoxy) ethenyl, 2- (AR 1) ethenyl or 2- (AR 2) ethenyl; or (TBdc) C 1-4 alkyl,. { optionally substituted as defined in (TBa) above, or by alkyl of C? _ 4S (0) pNH- or C 1-4 alkyl (0) p- (C? _4 alkyl) N- (p is 1 or 2)}; wherein Rv is hydrogen or C? _4 alkyl; Rw is hydrogen or C1-4 alkyl; Rv1 is hydrogen, alkyl C1-4 or C3_8 cycloalkyl; Rw1 is hydrogen, alkyl C1-4, C3-8 cycloalkyl, C1-4 alkyl-CO or C? _4S alkyl (0) q- (q is 1 or 2); or (TC) T is selected from the following groups: - (TCa) a fully saturated, optionally substituted 4-membered monocyclic ring containing a heteroatom selected from 0, N, and S (optionally oxidized), and linked by a nitrogen ring or carbon atom Sp3; TCb) an optionally substituted 5-membered monocyclic ring containing a heteroatom selected from 0, N and S (optionally oxidized), and linked via a nitrogen atom in the ring or a nitrogen atom in the sp3 or sp2 ring, whose monocyclic ring is completely saturated differently (where appropriate) to a bond sp2 carbon atom; (TCc) an optionally substituted 6 or 7 membered monocyclic ring containing 1 or 2 heteroatoms independently selected from O, N and S (optionally oxidized), and linked by means of a nitrogen atom on the ring or a nitrogen atom at the sp3 or sp ~ ring whose monocyclic ring is completely saturated other than (where appropriate) at a bound sp2 carbon atom; (TD) T is selected from the following groups: - (TDa) a spirobicyclic ring system containing 0, 1 or 2 rings of nitrogen atoms as the only heteroatom rings, the structure consists of a ring system of 5 or 6 members (attached by a ring of a nitrogen atom in the ring or a sp3 or sp2 carbon atom) substituted (but not adjacent to the bonding position) by a bound spiro carbon ring of 3, 4 or 5 members; whose bicyclic ring system is (i) fully saturated other than (where appropriate) at a bond sp2 carbon atom; (ii) contain a group N (RC) - in the ring system (at least two carbon atoms outside the bonding position when the bond is via a nitrogen atom or a sp2 carbon atom) or a group -N (RC) - in an optional substituent (not adjacent to the bonding position) and is (iii) optionally further substituted on a ring of available carbon atom; or (TDb) a 7-, 8- or 9-membered bicyclic ring system (attached by means of a ring nitrogen atom or a carbon atom ring Sp3 or sp2) containing 0, 1 or 2 rings of nitrogen atoms (and optionally an additional O or S ring heteroatom), the structure contains a bridge of 1, 2 or 3 carbon atoms; whose bicyclic ring system is (i) fully saturated other than (where appropriate) at a carbon atom sp2 carbon bond; (ii) contains a 0 or S heteroatom, or an -N (RC) group in the ring (at least two carbon atoms outside the bonding position when the bond is via a nitrogen atom or a hydrogen atom) carbon sp2) or a group -N (RC) - in an optional substituent (not adjacent to the bonding position) and is (iii) optionally further substituted on an available carbon atom ring; wherein RC is selected from the groups (RC1) to (RC5): (Rcl) C? -6 alkyl. { optionally substituted by one or more C1- alkanoyl groups (including disubstitution geminal disubstitution) and / or optionally monosubstituted by cyano, C1-4 alkoxy, trifluoromethyl, C4-4 alkoxycarbonyl, phenyl (optionally substituted as AR defined in the following ), alkyl of C? _4S (0) q- (q is 0, 1 or 2); or, except the first carbon atom of the C1-6 alkyl chain, optionally substituted by one or more groups (including geminal disubstitution) each independently selected from hydroxy and fluoro, and / or optionally monosubstituted by oxo, -NRvRw [in where Rv is hydrogen or C? -4 alkyl; Rw is hydrogen or C? _4alkyl], C alca-alca alkanoylamino, C alco _ alco alkoxycarbonylamino, C? _44-N-alkanoylamino C de -4 Nalkyl, C alquilo _4S (0) pNH- alkyl or alkyl of C? _4S (0) - (C? _4.N- alkyl (p is 1 or 2) 1; (Rc2) R13C0-, R13S02 or R13CS- where R are selected from (Rc2a) a (Rc2e ): (Rea) AR1, AR2, AR2a, AR2b, AR3, AR3a, AR3b, AR, AR4a, CY1, CY2; (Rc2b) hydrogen, C4-4 alkoxycarbonyl, trifluoromethyl, -NRvRw [where Rv is hydrogen or alkyl of C? -4; Rw is hydrogen or C? _4] alkyl, ethenyl, 2-alkyletenyl of C? -, 2-cyanohetenyl, 2-cyano-2- (C? -) ethenyl alkyl, 2-nitrohetenyl, 2-nitro-2- (Cx-4 alkyl) ethenyl, 2- (C 1 -4) alkylamino) ethenyl, 2- (C 1-4 alkoxycarbonyl) ethenyl, 2- (Al) ethenyl, 2- (AR 2) ethene 2- (AR2a) ethenyl (Rc2c) C alquilo _? Alquilo alkyl, optionally substituted by one or more groups (including geminal disubstitution) each independently selected from hydroxy, C?-10 alkoxy, C alco alkoxy ? _- alkoxy of C 1-4, C 1-4 alkoxy-C 1-4 alkoxy-C 1-4 alkoxy, C 1-4 alkanoyl and amino; and / or optionally substituted by a selected phosphonate group [phosphono, -P (0) (OH) 2, and mono- and di-alkoxy derivatives of C? _4 thereof, phosphinate [-P (OH) 2 and derivatives mono- and di-alkoxy of C? _ thereof), phosphoryl [-0-P (OXOH) 2, and mono- and di-alkoxy derivatives of C? _4 thereof], phosphoryl [-0-P (OH 2 and mono and di-alkyl derivatives of C? _4 thereof], cyano, halo, trifluoromethyl, alkoxycarbonyl of C? _4, C? -alkoxycarbonyl alkoxy of C? _4, C? -4 alkoxy of C? ~ 4-alkoxycarbonyl of C? _4, C? alkylamino? 4, di (C? 4) amino amino, C? _6 alkanoylamino, C? _4 alkoxycarbonylamino, C? _4 C? _4-N-alkanoylamino of C? _6 alkylaminocarbonyl, C? _4, C? _4) aminocarbonyl, C? _4S (0) pNH- alkyl, C 1-4 alkyl (O) p- (C? _4) alkyl N-, fluoro C 1-4 alkyl (O) pNH-, fluoroalkyl of C? _4S (0) p- (C? -4) N- alkyl, C? _4S alkyl (0) q-, CYl, CY2, ARl, AR2, AR3, ARl-O, AR2-0, AR3-0, AR1-S (O) q-, AR2-S (0) q-, AR3-S (0) q-, AR1-NH-, AR2-NH-, AR3-NH- (p is 1 or 2 and q is 0, 1 or 2), and also AR2a, AR2b, AR3a and AR3b versions of groups containing AR2 and AR3}; (Rc2d) R14C (O) O-alkyl of C? _6 wherein R14 is AR1, AR2, C? - alkylamino, benzyloxyC? _4 alkyl or C? -? Oalkyl. { optionally substituted as defined by (Rc2c)}; (Rc2ß) R150- wherein R15 is benzyl, C? - alkyl. { optionally substituted as defined by (Rc2c)} , CY1, CY2 or AR2b; (Rc3) hydrogen, cyano, 2-cyanoethenyl, 2-cyano-2- (C? _4 alkyl) ethenyl, 2- (Ci-4 alkylaminocarbonyl) ethenyl, 2- (C? _4) alkenyl ethenyl, 2- Nitroethenyl, 2-nitro-2- (C 1 -4 alkyl) ethenyl, 2- (AR 1) ethenyl, 2- (AR 2) ethenyl, or of the formula (Rc 3a) R16 (Rc3a) wherein X00 is -OR17, -SR17, -NHR17 and N (R17) 2; wherein R17 is hydrogen (When Xo0 is -NHR17 and -N (R17) 2), and R17 is C? - alkyl, phenyl or AR2 (When X00 is -OR17, -SR17 and -NHR17); and __ R16 is cyano, nitro, C alqu _ alkylsulfonyl, C4_ cycloalkylsulfonyl, phenylsulfonyl, C ?4 alkanoyl and C? -4 alkoxycarbonyl; (Rc4) trifly, AR1, AR2, AR2a, AR2b, AR3, AR3a, AR3b; (Rc5) RdOC (Re) = CH (C = 0) -, RfC (= 0) C (= 0) -, RgN = C (Rh) C (= 0) - or RiNHC (Rj) = CHC (= 0) - where Rd is C? _6 alkyl, - Re is hydrogen or C? -6 alkyl, or Rd and Re together they form an alkylene chain of C3_4; Rf is hydrogen, C? -6 alkyl, C? -6 hydroxyalkyl, C? _4alkyl of C? _6, NRvRw [wherein Rv is hydrogen or C? _4 alkyl; Rw is hydrogen or C? _] Alkyl, C? -6 alkoxy, C? _6 C6 alkoxy, C2-6 hydroxyalkoxy, C2_6 C? _ Alkoxy, C2_6 C? _4 alkoxy dialkylamino; Rg is C? _6 alkyl, hydroxy or Ci-β alkoxy; Rh is hydrogen or Ci-β alkyl; Ri is hydrogen, C? -6 alkyl, AR1, AR2, AR2a, AR2b and Rj is hydrogen or C? -6 alkyl; wherein AR 1 is an optionally substituted phenyl or optionally substituted naphthyl; AR2 is an optionally substituted 5 or 6 membered monocyclic heteroaryl ring, completely unsaturated (i.e. with the maximum degree of unsaturation) containing up to four heteoatoms independently selected from 0, N, and S (but not containing any of the 0- 0, 0-S or SS), and linked by means of a ring of carbon atom or a ring of carbon atom if the ring is therefore not quaternized; AR2a are a partially hydrogenated version of AR2 (ie AR2 systems that retain some, but not completely the degree of unsaturation), linked by means of a ring of carbon atom or linked by means of a nitrogen atom in the ring if the ring is therefore not quaternized; AR2b is a completely hydrogenated version of AR2 (ie AR2 systems that do not have unsaturation), linked by means of a ring of carbon atom or linked by means of a nitrogen atom in the ring; AR3 is an optionally substituted 8, 9 or 10 membered bicyclic heteroaryl ring, completely unsaturated (i.e. with the maximum degree of unsaturation) bicyclic heteroaryl ring containing up to four heteroatoms independently selected from 0, N and S (but not containing any of the OO, OS or SS bonds), and linked by means of a ring of carbon atom in any of the rings comprising the bicyclic system; AR3a is a partially hydrogenated version of AR3 (ie AR3 systems that retains some, but not the filling, degree of unsaturation), bound by means of a ring of carbon atom, or bonded by means of a nitrogen atom "in the ring if the ring is therefore not quaternized, in any of the rings comprising the bicyclic system, AR3b is a completely hydrogenated version of AR3 (ie AR3 systems which do not have unsaturation), bonded by means of a carbon atom, or linked by means of a nitrogen atom in the ring, in any of the rings, comprising the bicyclic system; AR4 is an optionally substituted tricyclic heteroaryl ring of 13- or 14-member completely unsaturated (ie with the maximum degree of unsaturation) containing ... up to four heteroatoms independently selected from 0, N and S (but does not contain any of the bonds 0-0, 0-S or SS), and joined by means of a ring of carbon atom in any of the rings comprising the tricyclic system; AR4a is a partially hydrogenated version of AR4 (ie AR4 systems that contain some, but not all, of the degree of unsaturation), linked by means of a ring of carbon atom, or linked by means of a nitrogen atom in the ring if the ring is therefore not quaternized, if any of the rings comprises the tricyclic system; - CY1 is an optionally substituted cyclobutyl, cyclopentyl or cyclohexyl ring, CY2 is an optionally substituted cyclopentyl or cyclohexyl ring.
2. 2. The compound of the formula (I), or a pharmaceutically acceptable salt, or a hydrolyzable ester in vivo, according to claim 1, characterized in that the 5-membered (fully unsaturated) heteroaryl ring system attached to optionally substituted N contains 1, 2 or 3 nitrogen atoms (the group (TAf) is selected from a group of the formula (TAfl) to (TAf6): - (TAfl) sAC) (TAO) wherein: R6 is selected (independently where appropriate) from hydrogen, C? _4 alkyl, C? -4 alkoxycarbonyl, C? _4 alkanoyl, carbamoyl and cyano; R 4 and R 5 are independently selected from hydrogen, halo, trifluoromethyl, cyano, nitro, C 1 alkoxy 4, C 1-4 alkyl (O) q- (q is 0, 1 or 2), C 4 -4 alkanoyl, C 1-4 alkoxycarbonyl, C 2-4 alkanoyloxy-C 1-4 alkyl, benzoxy-alkyl C? _4, C2_ alkanoylamino, -CONRvRw, NRvRw and C1-4 alkyl. { optionally substituted by hydroxy, trifluoromethyl, cyano, nitro, C 1-4 alkyl, C? _4S alkyl (0) q- (q is 0, 1 or 2), C? _4 alkoxycarbonyl, C 1-4 alkanoylamino, -CONRvRw, -NRvRw; wherein R v R w is hydrogen or C 4 alkyl; Rw is hydrogen or C? - alkyl}; or R4 is selected from one of the groups in (TAfa) to (TAfC) below, or (where appropriate) one of R4 and R5 is selected from the above list of values R4 and R5, and the other is selected from one of the groups in (TAfa) to (TAfc) following: - (TAfa) a group of the formula (TAfai; (TAfal) wherein Z ° is hydrogen or C? _4 alkyl; Xo and Y ° are independently selected from hydrogen, C? _ Alkyl, C? _4 alkoxycarbonyl, halo, cyano, nitro, C1-4S alkyl (0) q- (q is 0, 1 or 2), RvRwNS02- trifluoromethyl, pentafluoroethyl, C alca _ alkanoyl and CONRvRw [wherein Rv is hydrogen or C? _4 alkyl; Rw is hydrogen or C? _4 alkyl]; or one of Xo and Y ° is selected from the above list of the Xo and Y ° values, and the others are selected from phenyl, phenylcarbonyl, -S (0) q-phenyl (q is 0, 1 or 2), N - (phenyl) carbamoyl, phenylaminosulfonyl, AR2, (AR2) -CO, (AR2) -S (0) q- (q is 0, 1 or 2), N- (AR2) carbamoyl and (AR2) aminosulfonyl; wherein any phenyl group in (TAfa) can be optionally substituted by up to three substituents independently selected from C 1-4 alkyl, cyano, trifluoromethyl, nitro, halo and alkylsulfonyl of C1-4; (TAfb) an acetylene of the formula - = - H or - = - C1-4 alkyl; f2? fc; -X1-Y1-AR2, -X1-Y1-AR2a, -X1-Y1-AR2b, -X ^ Y1-AR3, -X ^ Y ^ ARSA or -X1-Y1-AR3b; wherein X1 is a direct bond or -CH (OH) - and Y1 is - (CH2) m-, - (CH2) n -NH- (CH2) m, -CO- (CH2) m-CONH- (CH2) »-, -C (= S) NH- (CH2) m- or -C (= 0) 0- (CH2) m-; or wherein X1 is -CH20-, -CH2NH- or -CH2N (C? _) alkyl- and Y1 is -C0- (CH2) m-, -CONH- (CH2) m- or -C (= S) NH- (CH2) m-; and further Y1 is -S02- when X1 is -CH2NH- or CH2N (C4-4 alkyl) - where n is 1, 2 or 3; m is 0, 1, 2 or 3 and q is 0.1 or 2; and when Y1 is - (CH2) m_NH- (CH2) m_ each m is independently selected from 0, 1, 2 or 3.
3. 3. The compound of the formula (I), or a pharmaceutically acceptable salt, or a hydrolyzable ester in vivo, according to claim 1, characterized in that the 7-, 8- or 9-member bicyclic ring system contains a bridge of 1, 2 or 3 carbon atoms (group (TDb) is selected from a group defined by the ring of skeletons shown in the formula (TDbl) a (TDbl4): - 7-member ring skeletons [4,1,0] [3,2,0] [3,1,1] [2.2,1] (TDb1) (TDb2) (TDb3) (TDb4) 8-membered ring skeletons [3,3,0] [ 4.2.0] [4.1.1] [3.2, 1] [2.2.2] (TDb5) (TDb6) (TDb7) (TDb8) (TDb9) 9 member ring skeletons [4,3,0] [5,2,0] [4,2,1] [3,3,1] [3,2,2] CTDblO) (TDb11) (TDb12) (TDb13) (TDb14) where; (i) the ring system contains 0, 1 or 2 rings of nitrogen atoms (and optionally an additional O or S ring heteroatom), and when the nitrogen ring is present, the heteroatom / heteroatoms 0 or S are in any different position as part of the 3-member ring (TDbl); (ii) the ring system is attached by means of a nitrogen atom in the ring or a ring of sp3 or sp2 carbon atom (with the double bond, where appropriate, oriented in any direction) from any position in the ring any ring [other than a bridge head position or a sp2 carbon atom in the 4-membered ring in (TDb2), (TDb6) and (TDb 11)]; (iii) one of the ring of carbon atoms in a position not adjacent to the bonding position is replaced (different when the ring contains an O or S heteroatom) by one of the following groups -NRc- [not in a head position] of bridge], > C (H) -NHRc, > C (H) -NRc-C alquilo4 alkyl, > C (H) -CH2-NHRc, > C (H) -CH2-NRc-C alquilo -4 alkyl [wherein the hydrogen atom shown in brackets is not present when the replacement is made in a bridge head position and where a chain link -CH2- central is optionally mono- or di-substituted by C? -4 alkyl; with the proviso that when the ring system is bonded by means of a nitrogen atom in the ring or a sp2 carbon atom any replacement of a ring of carbon atom by -NRc-, O or S is at least two carbon atoms outside the bonding position; and (iv) the ring system is optionally (further) substituted on a carbon atom ring available as per the bicyclic spiro ring systems described in (TDa); where Rc has any of the values listed in the above or in the following.
4. 4. The compound of the formula (I), or a pharmaceutically acceptable salt or an in vivo hydrolysable ester thereof, according to claim 1, characterized in that the groups defined in (TCa) a (TCc) are defined by the formula (TC1 a (TC4): - (TC1) (TC2) (TC3) (TC4) -where in (TC1): > A3-B3- es > C (Rq) -CH (Rr) - and G is -O-, -S-, -SO-, -S02- or > N (Rc); where in (TC2): ml is O, 1 or 2; > A3-B3- es > C = C (Rr) or > C (Rq) -CH (Rr) - and G is -O-, -S-, -SO-, -S02- or > N (Rc); where in (TC3): ml is O, 1 or 2; > A3-B3- es > C (Rq) -CH (Rr) (different when Rq and Rr are together hydrogen) and G is -O-, -S-, -SO-, -S02- or > N (Rc); where in (TC4): the ni is 1 or 2; ol is 1 or 2 and neither + ol = 2 or 3; > A3-B3- es > C = C (Rr) or > C (Rq) -CH (Rr) - or > N-CH2- and G is -O-, -S-, -SO-, -S02- or > N (Rc); Rp is hydrogen, C? _4 alkyl (different when such substitution is defined by> A3-B3-), hydroxy, C? _4 alkoxy or C? _4 alkanoyloxy; where in (TC1), (TC2) and (TC4); ml, ni and ol are as defined in the above: > A3-B3- es > N-CH2- and G is > C (R ^) (R> 112), > C = 0, > C-0H, > C-C4 alkoxy f > C = N-0H, > C = N-alkoxy of C? _4, > C = N-NH-alkyl of C? _, > C = NN ((C 1 4 alkyl) 2 (the latter two C 4 -alkyl groups in G being optionally substituted by hydroxy) or > C = NN-C 0 -C 4 alkoxy; where > represents two single bonds: Rq is hydrogen, hydroxy, halo, C1-4 alkyl or C1-4 alkanoyloxy, Rr is (independently where appropriate) hydrogen or C4_4 alkyl, R11 is hydrogen, alkyl of C? _4, fluoroalkyl of C? -4, alkyl of C? _4-thio-C? _4 alkyl or hydroxy-alkyl of C1-4 and R12 is - [C (Rr) (Rr) J ^ -N (Rr) (Rc) wherein m2 is 0, 1 or 2; and, different from the substituted ring defined by G, > A3-B3- and Rp, each ring system may optionally also be substituted on a carbon atom adjacent to the bond at > A3- up to two substituents independently selected from C 1-4 alkyl, fluoro-C 1-4 alkyl (including trifluoromethyl), C 1-4-thiol-C 1-4 alkyl, hydroxy-C 1-4 alkyl, amino, amino-C 1-4 alkyl, C 1-4 alkanoylamino, C? -4 alkanoylamino of C? _4 alkyl, carboxy, C 1-4 alkoxycarbonyl, AR-oxymethyl, AR-thiomethyl, oxo (= 0) (different when G is > N-Rc &Rc is of group (Rc2) defined in the above) or independently selected from Rc; and also hydroxy or halo (the last two optional substituents only when G is -0- or -S-); wherein AR is optionally substituted phenyl, C 1-4 phenylalkyl, optionally substituted naphthyl, 5- or 6-membered heteroaryl optionally substituted; wherein AR is also a bicyclic heteroaryl ring system of optionally substituted -5/6 or 6/6, in which the bicyclic heteroaryl ring system may be attached per half of an atom in any of the rings comprising the bicyclic system, and wherein the bicyclic mono- and heteroaryl ring systems are linked by means of a ring of carbon atom and can be (partially) hydrogenated; and wherein Rc is as defined in claim 1.
5. 5. The compound of the formula (I), or a pharmaceutically acceptable salt or an in vivo hydrolysable ester thereof, according to claim 1 and 4 wherein the groups in (TCa) a (TCc) are defined by the formulas (TC5) to (TC11): - (TC5) (TC6) (TC7) (TC8) (TC9) (TOO) (TC11) wherein Rc is as defined in claim 1.
6. 6. The compound of the formula (I) according to claim 1 and 4, characterized in that a compound of the formula (IB), or a pharmaceutically acceptable salt, or an in vivo hydrolysable ester thereof (IB) wherein HET is pyridin-2-yl or pyrazin-2-yl (especially pyridin-2-yl); R2 and R are independently hydrogen or fluorine; and Rpl and Rp2 are independently hydrogen, hydroxy, bromine, C? _4 alkyl, carboxy, C? _4 alkoxycarbonyl, hydroxymethyl, C? _4 alkoxymethyl or carbamoyl; or pharmaceutically acceptable salts thereof.
7. The compound according to claim 1 and 4, characterized in that 5 (R) -Pyrid-2-yloxymethyl-3- (4- (4- (5-cyanopyrid-2-yl) piperazin-1-yl) - 3-fluorophenyl) oxazolidin-2-one; 5 (R) - (6-chloropyridazin-3- (4- (4- (5-cyanopyrid-2-yl) piperazin-1-yl) -3-fluorophenyl) oxazolidin-2-one; 5 (R) -Pirazin -2-yloxymethyl-3- (4- (4- (5-cyanopyrid-2-yl) piperazin-1-yl) -3-fluorophenyl) oxazolidin-2-one; 5 (R) -Pyrimidin-4-yloxymethyl- 3- (4- (4- (5-cyanopyrid-2-yl) piperazin-1-yl) -3-fluorophenyl) oxazolidin-2-one; 5 (R) -Pyridazin-3-yloxymethyl-3- (4- (4- (5-cyanopyrid-2-yl) piperazin-1-yl) -3-fluorophenyl) oxazolidin-2-one; 5 (R) -Pyrid-2-yloxymethyl-3- (3-fluoro-4- ( 3,6-dihydro- (2H) -pyran-4-yl) phenyl) oxazolidin-2-one; 5 (R) - (4-methylpyrid-2-yloxymethyl) -3- (3-fluoro-4- (3 , 6-dihydro- (2H) -pyran-4-yl) phenyl) oxazolidin-2-one; 5 (R) - (3-methylpyrid-2-yloxymethyl) -3- (3-fluoro-4- (3, 6-dihydro- (2H) -pyran-4-yl) phenyl) oxazolidin-2-one; 5 (R) - (6-chloropyridazin-3-yloxymethyl) -3- (3-fluoro-4- (3,6) -dihydro- (2H) -pyran-4-yl) phenyl) oxazolidin-2-one; 5 (R) -Pyridazin-3-yloxymethyl-3- (3-fluoro-4- (3,6-dihydro- (2H) ) -piran-4-yl) phenyl) oxazolidin-2-one; 5 (R) -Piri midin-4-yloxymethyl-3- (3-fluoro-4- (3,6-dihydro- (2H) -pyran-4-yl) phenyl) oxazolidin-2-one; 5 (R) -Pirazin-2-yloxymethyl-3- (3-fluoro-4- (3,6-dihydro- (2H) -pyran-4-yl) phenyl) oxazolidin-2-one; 5 (R) - (5-chloropyridin-2-yloxymethyl) -3- (3-fluoro-4- (3, & -dihydro- (2H) -pyran-4-yl) phenyl) oxazolidin-2-one; and pharmaceutically acceptable salts thereof.
8. 8. The compound according to claim 1 and 4, characterized in that 5 (R) -Pyrid-2-yloxymethyl-3- (3-fluoro-4- (3,6-dihydro (2H) -pyran-4-yl) phenyl oxazolidin-2-one; 5 (R) -Pirazin-2-yloxymethyl-3- (3-fluoro-4- (3,6-dihydro (2H) -pyran-4-yl) phenyl) oxazolidin-2-one; or pharmaceutically acceptable salts thereof.
9. 9. The process for the preparation of a compound of the formula (I) according to claim 1 or a pharmaceutically acceptable salt or hydrolysable esters in vivo, the process comprising of (a) to (f): - (a) modifying a substituent on or introducing a substituent into another compound of the formula (I): (b) reacting a compound of the formula (II) (H) wherein Yp is hydroxy with a compound of the formula (bl) HET-OH or (b2) HET-Lg, wherein Lg is a suitable leaving group; (c) reacting a compound of the formula (II) wherein Yp is a leaving group, with a metal alkoxide compound of the formula HET-OM wherein M is an alkali metal, or other metal known to promote O-alkylation; (d) reacting a compound of the formula Q-Zp wherein Zp is an isocyanate or amine group with an epoxide of the formula CH2 (0) CH-CH20-HET; (e) where X is -S- using an analogous process to process (c) wherein (the) a metal oxide compound of the formula HET-SM where M is an alkali metal, or other metal known to promote S-alkylation; or using (e2) HET-SH and a compound of the formula (II) in which Yp is a suitable leaving group; (f) reacting a urethane compound of the formula (III) with a compound of the formula (IV) O (III) (IV) wherein R .21 is C? _6 alkyl or benzyl; and hereinafter if necessary: (i) eliminate any protective groups; (ii) forming a pharmaceutically acceptable salt; (iii) forming a hydrolysable ester in vivo. The method for producing an antibacterial effect in a warm-blooded animal of the formula (I) according to claims 1 to 8, or a pharmaceutically acceptable salt, or an in vivo hydrolysable ester thereof. The compound of the formula (I) according to claims 1 to 8, or a pharmaceutically acceptable salt, or an in vivo hydrolysable ester thereof, for use as a medicament. The use of a compound of the formula (I) according to claims 1 to 8, or a pharmaceutically acceptable salt, or an in vivo hydrolysable ester thereof, in the manufacture of a medicament for use in the production of a antibacterial effect in a warm-blooded animal. The pharmaceutical composition comprising a compound of the formula) I) according to claims 1 to 8, or a pharmaceutically acceptable salt, or a hydrolyzable ester in vivo and a pharmaceutically acceptable solvent or carrier. EXTRACT Compounds of the formula (I), or a pharmaceutically acceptable salt, or an in vivo hydrolysable ester thereof, wherein, for example, X is -O- or -S-; HET is a 6-membered heteroaryl ring attached to optionally substituted C contains 1 or 2 N atoms; Q is selected from, for example, (Q1) and (Q2); R2 and R3 are independently hydrogen or fluoro; T is selected from a range of groups, for example, a 5-membered (fully unsaturated) heteroaryl ring system attached to N or a 3,6-dihydro- (2H) -pyran-4-yl group or a group 4- substituted pyrazino are useful as antibacterial agents; and processes for their manufacture and pharmaceutical compositions containing them.