MXPA01003509A - Heterocyclyl amino methyloxa zolidinones as antibacterials - Google Patents

Abstract

Compounds of formula (I), or a pharmaceutically-acceptable salt, or an in-vivo-hydrolysable ester thereof, wherein, for example, HET is an optionally substituted C-linked 5-membered heteroaryl ring containing 2 to 4 heteroatoms independently selected from N, O and S;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 group of formula (TC5):wherein Rc is, for example, R13CO-, R13SO2- or R13CS-;wherein R13 is, for example, optionally substituted (1-10C)alkyl or R14C(O)O(1-6C)alkyl wherein R14 is optionally substituted (1-10C)alkyl;are useful as antibacterial agents;and processes for their manufacture and pharmaceutical compositions containing them are described.

Description

A INO METI OXA HETEROCICLYL ZOLIDINONES AS AN ANTABACTERIALS 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 ineffective. 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. Pathogens - Gram positive, 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 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 provides a pharmacophore previously active less effective or redundant, 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 new 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 resistant to aminoglycosides and clinically ß-lactams used. Accordingly, the present invention provides a compound of formula (I), or a pharmaceutically acceptable salt, or an in vivo hydrolysable ester thereof, O Q-N A O X - @ (I) wherein HET is a heteroaryl ring of linked members containing 2 to 4 heteroatoms independently selected from N, O and S, which ring is optionally substituted on an available carbon atom by 1 or 2 substituents independently selected from C? _4 alkyl, amino, C? _4 alkylamino, C? _4 alkyl, C? -4 alkoxycarbonyl, and halogen; and / or an available nitrogen atom (with the condition of the ring is therefore not quaternized) by C? -4 alkyl; or HET is a 6-membered C-linked heteroaryl ring containing 2 or 3 nitrogen heteroatoms, which ring is optionally substituted on any available C atom by 1, 2, or 3 substituents independently selected from C? _, amino, alkylamino of C? _4, C? _4 alkoxy, C? _ alkoxycarbonyl, and halogen; Q is selected from Ql to Q9: Ql Q2 Q3 Q4 Q5 Q6 Q7 Q8 Q9 wherein R and R are independently hydrogen or fluoro; wherein i is carbon or nitrogen; Bx is O or S (or, in Q9 only, NH); Xq is 0, S or N-R1 (wherein R1 is hydrogen, C ?4 alkyl or hydroxyC de ?4 alkyl); and where in Q7 each Ai is independently selected from carbon or nitrogen, with a maximum of 2 nitrogen heteroatoms in the 6-membered ring, and Q7 is bound 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 is bound to T by either of the carbon atoms specified in the 5-membered ring and bonded to the benzo ring by means of either the two carbon atoms specified on either side of the bond bonds shown; and Q9 is linked via either of the two specified carbon atoms on either side of the bond bond shown; where T is selected from the groups in (TA) to (TD) 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) AR1-C0, AR2-C0, AR3-C0, AR4-C0; (TAd) AR1-0-, AR2-0-, AR3-0-; (TAe) ARl S (0) q-, AR2-S (0) q-, AR3-S (O) 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? _4 alkoxy, C? _4 alkanoyl, cyano, halo, trifluoromethyl, C? _4 alkoxycarbonyl, NRvRw, C? -6 alkanoylamino, C? -alkoxycarbonylamino -4 -4, N-C ?4-N-C alca-6-alkanoylamino alkyl, C? _4S alkyl (0) q- (q is 0, 1 or 2), CY1, CY2 or AR1}; (TBb) -NRv1Rw1; . (TBc) ethenyl, 2-C2-4 alkyletenyl, 2-cyanoethenyl, 2-cyano-2- (C4-4 alkyl) ethenyl, 2-nitroethenyl, 2-nitro-2- (C4-4 alkyl, ) ethenyl, 2- (C 1 -4) alkylaminocarbonyl ethenyl, 2- ((C 1 -4) alkenyl ethenyl, 2- (AR 1) ethenyl, 2- (AR 2) ethenyl;, 10,, 10c (TBd) O- , RluS (0) q- (q is 0, 1 or 2) or R10CS- where R10 is selected from the following groups: - (TBda) CY1 or CY2; (TBdb) hydrogen, C4-4 alkoxycarbonyl, trifluoromethyl, -NRvR, ethenyl, 2- (C4-4 alkyletenyl, 2-cyanoethenyl, 2-cyano-2- (C4-4 alkyl) ethenyl, 2-nitropenyl, 2-nitro-2- (C4-4 alkyl) ethenyl, 2- (C 1-4 alkylaminocarbonyl) ethenyl, 2- (alkoxycarbonyl C? _4) ethenyl, 2- (AR 1) ethenyl or 2- (AR 2) ethenyl; or (TBdc) alkyl of C? _4,. { optionally substituted as defined in (TBa) above, or by C 1-4 alkyl (0) pNH- or C? -S (O) p- alkyl (C? -4 alkyl) N- (p is 1 or 2)}; wherein Rv is hydrogen or C? - alkyl; Rw is hydrogen or C? _4 alkyl; Rv1 is hydrogen, C? _4 alkyl or C3_e cycloalkyl; Rw1 is hydrogen, alkyl C1-4, C3_8 cycloalkyl, C1-4 alkyl-CO or alkyl of C1-4S (O) 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 1 heteroatom selected from 0, N, and S (optionally oxidized), and linked by a ring nitrogen or carbon atom sp3; (TCb) an optionally substituted 5-membered monocyclic ring containing 1 heteroatom selected from 0, N and S (optionally oxidized), and linked by means of a nitrogen atom in the ring or a nitrogen in the sp3 or sp2 ring, whose monocyclic ring is completely saturated differently (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 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 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 (joined by means of a ring of a nitrogen atom in the ring or an atom of sp3 or sp2 carbon) substituted (but not adjacent to the bonding position) by a spiro-bonded 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) - on 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-member bicyclic ring system (attached by means of a ring nitrogen atom or a sp3 or sp2 carbon atom ring) 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 an O or S heteroatom, or an -N (RC) group on 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 alkanoyl groups of C? _ (including geminal disubstitution) and / or optionally monosubstituted by cyano, C? -4 alkoxy, trifluoromethyl, C? _4 alkoxycarbonyl, 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, -NRvR [wherein Rv is hydrogen or C? _4 alkyl; Rw is hydrogen or C? 4 alkyl, C? -6 alkanoylamino, C? -4 alkoxycarbonylamino, C? -4-N-C3-4 alkanoylamino-C4 alkyl, C? 4S (0) pNH- or C3-S4 alkyl (O) p- (C? _) Alkyl N- (p is 1 or 2) }; (Rc2) R13C0-, R13S02 or R13CS - wherein R13 are selected from (Rc2a) to (Rc2e): - (Rc2a) 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 C? _4] alkyl, ethenyl, 2-alkyletenyl of C? _4, 2-cyanoethenyl, 2-cyano-2- (C? _4 alkyl) ethenyl, 2-nitro-tennyl, 2-nitro-2- (C 4 alkyl) ethenyl, 2- (C 1 -4) alkylamino etyl, 2- (C 4 _ 4 alkoxy) ethenyl, 2- (AR 1) ethenyl, 2- (AR 2) ethenyl, 2- (AR 2a) ethenyl; (Rc2c) C1-10 alkyl. { optionally replaced by one or more groups (including 'geminal disubstitution') each independently selected from hydroxy, C1-10 alkoxy, C? _ alkoxy from C? _4 alkoxy, C? -4-alkoxy from C? _4-C1-4 alkoxy, C? _4 alkanoyl, phosphoryl [-OP (O) (OH) 2 (and mono- and di-Cxi-alkoxy derivatives thereof], phosphoryl [-0-P (OH) 2 and mono- and di-alkyl derivatives of C? _4 thereof], and amino and / or optionally substituted by a group selected from phosphonate [phosphono, -P (O) (OH) , and mono- and di-alkoxy derivatives of C? _4 thereof], phosphinate [-P (OH) 2 and mono- and di-alkoxy derivatives of C1-], cyano, halo, trifluoromethyl, alkoxycarbonyl C 1-4, C 1-4 alkoxy C 1-4 alkoxycarbonyl, C 1-4 alkoxy C 1-4 alkoxy C 1-4 alkoxycarbonyl, C 1-4 alkylamino, di (C? 4 alkyl) amino, C alca-α alkanoylamino, C 1-4 alkoxycarbonylamino, C? -4-C alca -4-N-alkanoylamino C 1-6 alkanoylamino, C 1-4 alkylaminocarbonyl, di (C? _4) aminocarbonyl, C1-4S (O) pNH-, C1-4S alkyl (0) p- (C4-4 alkyl) N-, fluoro C1-4S (O) PNH- alkyl, C1-4S (O) fluoroalkyl - (C? _4) N- alkyl, C? _4S (0) q- alkyl, [the C? _4 alkyl group of C? _4S (0) _ which is optionally substituted by a substituent selected from hydroxy , C 1-4 alkoxy, C? -4 alkanoyl, phospho nyl [-OP (O) (0H) 2 and mono- and di-alkoxy derivatives of C? _4 thereof], phosphoryl [-0-P (0H) 2 and mono- and di-alkoxy derivatives of C? _4 of them], amino, cyano, halo, trifluoromethyl, alkoxycarbonyl of C? _4, C? -4 alkoxy of C 1-4 alkoxy of C? -4-alkoxy of C 1-4-alkoxycarbonyl of C 1-4, carboxy, C? _4 alkylamino, C? _4 dialkyl, amino, C? _ e alkylamino, C? _4 alkoxycarbonylamino, C? -4-N-C 1-6 alkanoylamino N-alkyl, C? _4 alkylaminocarbonyl , dialkyl of C? _4, aminocarbonyl, C? -4S (O) PNH- alkyl, C? -4S (0) p- (C? _4) N- alkyl, C? -4S alkyl (0) ) q-, AR1-S (0) q, AR2-S (0) q-, AR3-S (0) q, and also versions AR2a, AR2b, AR3a and AR3b of groups containing AR2 and AR3}; CYl, CY2, ARl, AR2, AR3, ARl-O-, AR2-0-, AR3-0-, AR1-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 versions AR2a, AR2b, AR3a and AR3b of the groups containing AR2 and AR3}; (Rc2d) Ri4C (0) O-alkyl of Cx_6 wherein R 114"is AR1, AR2, C4-4 alkylamino (the C4_4 alkyl group which is optionally substituted by alkoxycarbonyl or by carboxy), C14-benzyloxy-alkyl Or optionally substituted C alquilo _? Alquilo alquilo alkyl, as defined by (Rc2c)} 0; (Rc2e) R150- wherein R15 is benzyl, C alquilo _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, -nitroetenilo, 2-nitro-2- (C? _4) ethenyl, 2- (ARl) ethenyl, 2- (AR2) ethenyl, or of the formula (Rc3a) (Rc3a) wherein X00 is -OR17, -SR17, -NHR17 and -N (R17) 2; wherein R17 is hydrogen (when X00 is -NHR17 and -N (R17) 2), and R17 is C1-4 alkyl, phenyl or AR2 (when X00 is -OR17, -SR17 and -NHR17); and R 16 is cyano, nitro, C 1-4 alkylsulfonyl, C 4 cycloalkylsulfonyl, phenylsulfonyl, C 1-4 alkanoyl and C 1-4 alkoxycarbonyl; (Rc4) trifile, 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) ) - wherein 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, hydroxyalkyl C? ? 6, C? _6alkyl of C? _6, NRvRw [where Rv is hydrogen or C? _ Alkyl, Rw is hydrogen or C? _4 alkyl], C? -6 alkoxy, C6-alkoxy C? _6, C2_6 hydroxyalkoxy, C2_6 C? _4alkoxy alkylamino, C2_6 C? _4 alkoxy dialkylamino, Rg is C? _6 alkyl, hydroxy or C? _6 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 .AL 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 heteroatoms independently selected from 0, N, and S (but not containing any of the 0-0 bonds) , OS or SS), and linked by means of a ring of carbon atom or a ring of nitrogen 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 bicyclic heteroaryl ring of 8, 9 or 10 members, completely unsaturated (ie with the maximum degree of unsaturation) containing up to four heteroatoms independently selected from 0, N and S (but not containing any of the 0 bonds). -0, 0-S or SS), 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 completely, degree of unsaturation), bound by a ring of carbon atom, or linked 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 fully hydrogenated version of AR3 '(ie AR3 systems which have no unsaturation), bonded by means of a carbon atom, or united by means of 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 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 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) in a sp2-linked carbon atom it is understood that the ring is linked by medium of a bond of the carbon atoms in a double bond C = C. In another embodiment, (Rcl) is as previously defined different from the optional phenyl substituent on C? _6 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 such as C? -? o- (TAf) alkyl Where T is an optionally substituted heteroaryl ring system N linked (fully unsaturated) of 5 members containing 1, 2 or 3 nitrogen atoms, is preferably selected from a group of the following formula (TAfl) to (TAfd) (particularly (TAfl), (TAf2), (TAf4) and (TAf5), and especially (TAfl) and / or (TAf2)). The above preferred values of (TAf) are particularly preferred when presenting in Q1 or Q2, especially Q1.

(TAf4) (TAl5) (TAf6) wherein: R6 is selected (independently where appropriate) from hydrogen, C4_4alkyl, C4_4alkoxycarbonyl, C4_4alkanoyl, carbamoyl and cyano; R and R5 are independently selected from hydrogen, halo, trifluoromethyl, cyano, nitro, C? 4 alkoxy, C? _4S alkyl (0) q- (q is 0, 1 or 2), C? _4 alkanoyl, alkoxycarbonyl of C? -4, C2_4 alkanoyloxy-C? _4 alkyl, benzoxy-C? _4 alkyl, C2_4-alkanoylamino, -CONRvRw, -NRvRw and C? _4 alkyl. { optionally substituted by hydroxy, trifluoromethyl, cyano, nitro, C? _ alkyl, C? _4S alkyl (0) q- (q is 0, 1 or 2), C? _4 alkoxycarbonyl, C? _4 alkanoylamino, - CONRvRw, -NRvRw; wherein R v R w is hydrogen or C 4 alkyl; Rw is hydrogen or alkyl C? -4); or R4 is selected from one of the following groups in (TAfa) to (TAfc), 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 (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? -4S alkyl (0) q- (q is 0, 1 or 2), RvRwNS02-trifluoromethyl, pentafluoroethyl, C 1-4 alkanoyl and -CONRvRw [wherein Rv is hydrogen or C? - 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 (O) 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; where any phenyl group in (TAfa) can optionally be substituted for up to three substituents independently selected from alkyl of C1-4, cyano, trifluoromethyl, nitro, halo, and alkylsulfonyl of C? _4; (TAfb) an acetylene of the formula - = - H or - = - C? -4 alkyl; (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 Y1 is - (CH2) m-, - (CH2) n -NH- (CH2) m, -CO- (CH2) m-CONH- (CH2) m-, -C (= S) NH- (CH2) m- or -C (= 0) 0- (CH2) m-; or wherein X1 is - (CH2) - or - CH (Me) - (CH2) m and Y1 is - (CH2) m -NH- (CH2) m-, -CO- (CH2) m-, CONH- (CH2) ) ra-, -C (= S) NH- (CH2) m-, -C (= 0) 0- (CH2) m- or -S (O) q- (CH2) m-; or wherein X1 is -CH20-, -CH2NH- or -CH2N (C1-4 alkyl) - and Y1 is -C0- (CH2) m-, -C0NH- (CH2) m- or -C (= S) NH - (CH2) m-; and further Y1 is -S02- when X1 is -CH2NH- or -CH2N (C1-4 alkyl) - and Y1 is - (CH2) m- where X1 is -CH20- or -CH2N C1-4 alkyl-; where n is 1, 2 or 3; m is 0, 1, 2 or 3 and q is 0, 1 or 2; and where 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, as -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 C1-4 alkyl, and R4 and R5 are independently selected from hydrogen, C1- alkyl 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. More preferably it is (TAf2) with such preferred substituents. (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 previous values of (TAg) are particularly preferred when present in Q1 or Q2, especially Q1. < TAg1) (TAg2) (TAg3) wherein R7 is selected from (TAga) hydrogen, C? _4 alkyl. { optionally substituted by one or two substituents (excluding geminal disubstitution) independently selected from fluoro, hydroxy, C? -4 alkoxy and -NRvRw]}; or (TAgb) R8-0-, R8-S-, R8-NH- or R8R8-N; wherein R8 is selected (independently where appropriate) from hydrogen, C3-4alkyl or C3-g cycloalkyl. { both optionally substituted by one or two substituents (excluding geminal disubstitution) independently selected from hydroxy, C? -4 alkoxy, C? -4 alkoxycarbonyl and NRvRw} , C2_4 alkenyl,. { optionally substituted by one or two substituents -NRvRw} , C? _ alkanoyl. { optionally substituted by one or two substituents independently selected from -NR v R w and hydroxy} , phenyl-C 1 -4 alkyl or pyridyl-C 4 alkyl. { the phenyl and pyridyl (preferably pyridin-4-yl) are optionally substituted by one or two substituents -NR v R w}; or (TAgc) morpholino, thiomorpholino, pyrrolidino . { optionally and independently substituted in the 3- and / or 4- positions by C? -4 alkyl} , piperidino substituted in the 4-position by R9-, R9-0-, R9-S-, R9-NH- or R9R9-N-; wherein R9 is selected (independently where appropriate) from hydrogen, C? _4 alkyl. { optionally substituted by one or two (excluding geminal disubstitution) hydroxy, C? _4 alkoxy, C? _4 alkoxycarbonyl, or -NRvRw} and piperazine. { optionally substituted in the 4-position by C? _4 alkyl, C33 cycloalkyl, C? -4 alca alkanoyl, C? -44 alkylsulfonyl C alco _4 alkoxycarbonyl, and optionally and independently substituted in the 3- and / or 5-position - by C1-4 alkyl}; wherein Rv is hydrogen or C 1 -4 alkyl; Rw is hydrogen or C? - alkyl. (TC) Preferred values for the optional substituents and the groups defined in (TCa) to (TCc) are defined by the formula (TCl) a (TC4): - where in (TC1): > A3-B3- es > C (Rq) -CH (Rr) - and G is -0-, -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 -O-, -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 -O-, -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 -O-, -S-, -SO-, -S02- or > N (Rc); R p is hydrogen, C 4 alkyl (different when such substitution is defined by > A3-B 3 -), hydroxy, C 4 alkoxy, or C 4 4 alkanoyloxy; where in (TC1), (TC2) and (TC4); ml, ni and ol are as defined in the above: > A3-B- is > N-CH2- and G is > C (R) (R12), > C = 0, > C-0H, > C 1-4 -alkoxy, > C = N-OH, > C = C 1-4 -alkoxy, > C = N-NH-C-4 alkyl, > C = NN ((C 4 alkyl) 2 (the last two C 1-4 alkyl groups above in G being optionally substituted by hydroxy) or > C = NN-CO-C 4 alkoxy; > represents two simple links; Rq is hydrogen, hydroxy, halo, C? _4 alkyl or C? _4 alkanoyloxy; Rr is (independently where appropriate) hydrogen or C 4 alkyl; R11 is hydrogen, C? _4 alkyl, fluoroalkyl C? -4, C? _4-thio-alkyl of C? _4 alkyl or hydroxy-C1-4 alkyl and R12 is - [C (Rr) (Rr) l ^ -N (Rr) (Rc) where 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? -4 alkyl, C? _4 fluoroalkyl (including trifluoromethyl), C? _4-thiol-C? _ Alkyl, hydroxy-C? _4 alkyl, amino, amino -alkyl of C? _4, alkanoylamino of C? _4, alkanoylamino of C? _4-alkyl of C? _4, carboxy, alkoxycarbonyl of C? _4, AR-oxymethyl, AR-thiomethyl, oxo (= 0) (different when G it's >; N-Rc and 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 -O- or -S-); where AR (or ARp) is as defined by the following formula (IP); Rc is selected from the groups (Rcl) to (Rc5) defined in the above. For evasion of doubt, () m ?, () ni and () oí indicate (-CH2-) m ?, (-CH2-) n? and (-CH2-) oi, respectively (optionally substituted as described 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 (R1: 1) (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 R13CO-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 present in Q1 or Q2, especially Q1, (especially when HET is isoxazole). (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.

(TDa1) (TDa2) (TDa3) (TDa4) (TDa5) (TDa6) (TDa7) (TDaß) (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 (ü) 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-C1-4 alkyl, > CH-CH2-NHRc, > CH-CH2-NRc-C1-4 alkyl [wherein a central -CH2- chain link is optionally mono- or di-substituted by [C1-4 alkyl]; provided that the positions marked with * are not replaced by -NH- in the ring containing A4 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 alkyl, C1-4 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 alkanoylamino, 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 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 [different from a bridge head position or a sp2 carbon atom in the 4-membered ring in (TDb2), (TDb6) and (TDb 11)]; (iii) one of the carbon atoms in the ring at 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 one position] from bridgehead], >; C (H) -NHRc, > C (H) -NRc-C alquilo4 alkyl, > C (H) -CH2-NHRc, > C (H) -CH2-NRc-C-alkyl [wherein the hydrogen atom shown in brackets is not present when the replacement is made in a bridgehead position and where a central chain -CH2- bond 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 (in addition) substituted on a ring of carbon atom available by 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 bridge head 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 present in Q1 or Q2, especially Q1.

(TDb4a &b) (TDb8) (TDb9) In another embodiment, a compound of formula (I) which is defined by the following formula (IP) is provided: (IP) wherein T1 is a C-linked isoxazole ring which is optionally substituted at any available C atom by 1 or 2 substituents independently selected from C? _4alkyl, amino, C? _4alkylamino, C? _4alkoxy, and halogen; What is it R2 and R3 are independently hydrogen or fluoro; Rp6p is hydrogen, C 4 alkyl, hydroxy, C 1 alkoxy or C 2 alkanoyloxy; > A-B is of the formula > C = C (Ra) -, > CHCHRa-, C (OH) CHRa- or > N-CH2- (> represents two single bonds) wherein Ra is hydrogen or C? _4 alkyl; D is O, S, SO, S02 or NR7p; R4p and R5p are independently oxo (= 0) [but not when R7p is of the following group (PC)], C? _4 alkyl, C? -4 alkanoylamino of C? _4 alkyl, hydroxyC de ?4 alkyl , carboxy, C4-4 alkoxycarbonyl, AR-oxymethyl, AR-thiomethyl (wherein AR is as defined in the following) or independently as defined by R7p in the following with the proviso that R4p and R5p are not phenyl, benzyl, AR (as defined in the following), a tetrazole, cyclopentyl or cyclohexyl ring system; and when D is 0 or S, R4p and R5p are additionally independently hydroxy or bromine; wherein R7p is selected from (PA) to (PE) :-( PA) hydrogen, cyano, 2- (C 1-4 alkoxycarbonyl) ethenyl, 2-cyanohetenyl, 2-cyano-2- (C? 4) ethenyl, 2- (C4-4) alkylaminocarbonyl ethenyl; (PB) phenyl, benzyl, AR (as defined in the following) or a tetrazole ring system [optionally mono-substituted at the 1 6 2 position of the tetrazole ring by C 1 -4 alkyl, C 2 -4 alkenyl, C 2 alkynyl -4 or C 1-4 alkanoyl] wherein the tetrazole ring system binds to nitrogen in > NR7p for a ring of carbon atom; (PC) R10PCO, R10pSO2- or R ^ CS- wherein R10p are selected from (PCa) a (PCf): (PCa) ARp (as defined in the following); (PCb) cyclopentyl or cyclohexyl, 1,3-dioxolan-4-yl, 1,3-dioxan-4-yl or 1,4-dioxan-2-yl [optionally mono- or disubstituted independently by substituents independently selected from alkyl of C? _4 (including geminal disubstitution), hydroxy (but excluding 1,3-dioxolan, -4-yl, 1,4-dioxan-2-yl and 1,3-dioxan-4-yl substituted by hydroxy), alkoxy C? _4, alkylthio, C? _4 alkanoyl, cyano and trifluoromethyl]; (PCc) hydrogen, C? _4 alkoxycarbonyl, trifluoromethyl, amino, C? _4 alkylamino, di (C? -4) amino alkyl, 2- (5- or 6- membered heteroaryl) ethenyl, 2- (heteroaryl) from - or 6- (partially) hydrogenated members) ethenyl, 2-phenylethenyl [wherein the heteroaryl or substituted phenyl is optionally substituted at one available carbon atom by 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? -10 alkoxy, trifluoromethyl, C? -4 alkoxy of C 1-4 alkoxy, C? _4 alkoxy C? _4 alkoxy-C 1-4 alkoxy, C 1-4 alkanoyl, alkoxycarbonyl of C? -4,. C 1-4 alkylamino, di (C 1-4 alkyl) amino, C? _6 alkanoylamino, C 1-4 alkoxycarbonylamino, C? _4-N-C2_g alkanoylamino N-alkyl, C 1-4 alkyl (O) pNH-, C 1-4 alkyl (O) p- (C 1-4 alkyl) N-, C 1-4 fluoroalkyl (0) PNH-, fluoro C 1-4S (O) p alkyl (C? _4) N-, phosphono, C 1-4 alkoxy (hydroxy) phosphoryl, C 1-4 di-alkoxyphosphoryl, C? -4S (0) q- alkyl, phenyl, naphthyl, phenoxy, naphthhoxy, phenylamino, naphthylamino, phenyl (O) q-, naphthyl (O) q- [wherein such phenyl and naphthyl groups are optionally substituted by up to three substituents independently selected from C 1-4 alkoxy, halo and cyano], or CYP (as defined in the following ), where p is 1 or 2 and q is 0, 1 or 2]; (PCe) RllpC (O) Oalkyl of C? _6 wherein Rllp is an optionally substituted 5- or 6-membered heteroaryl, optionally substituted phenyl, C 1-4 alkylamino, C 1-4 benzyloxyalkyl or C 1-10 alkyl optionally replaced; (PCf) R12p0- wherein R12p is benzyl or optionally substituted C6-6alkyl; (PD) RdOC (Re) = CH (C = 0), RfC (= 0) C (= 0) -, RgN = C (Rh) C (= 0) or RiNHC (Rj) = CHC (= 0) - , wherein Rd is C? _6 alkyl; Re is hydrogen or C? -6 alkyl or Rd and Re together form an alkynylene chain of C3-4; Rf is hydrogen, C6_6alkyl, C6_6-hydroxyalkyl, C6_6alkoxy-C6_6alkyl, amino, C4_4alkylamino, C1_4alkylamino, alkoxy of C? _6, C? -6-alkoxy of C? _6, hydroxy-alkoxy of C2_e, alkylamino of C? -4_alkoxy of C2_6, di-alkylamino of C? -4 alkoxy of C2_6; R9 is C6-6alkyl, hydroxy or Ci-βalkoxy; Rh is hydrogen or C? _6 alkyl; R1 is hydrogen, optionally substituted C ?_6 phenyl alkyl or an optionally substituted 5- or 6-membered heteroaryl [and (partially) hydrogenated from the versions thereof] and Rj is hydrogen or C? _6 alkyl; (PE) R13PCH (R13p) (CH2) mp_ where mp is O or 1; R1 p are fluorine, cyano, C4-4 alkoxy, C1-4 alkylsulfonyl, C4-4 alkoxycarbonyl or hydroxy, (with the proviso that when mp is 0, R, 14P is not fluorine or hydroxy) and R is hydrogen or C] alkyl; wherein ARp is optionally substituted phenyl, optionally substituted 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 linked via 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 carbon atom ring and can be (partially) hydrogenated; wherein Cyp is selected from: - (i) 4-, 5- or 6-membered cycloalkyl ring; (ii) 5- or 6-membered cycloalkenyl ring; (iii) 5- or 6-membered heteroaryl, 5- or 6-membered heteroaryloxy, heteroaryl (0) q-, 5- or 6-membered heteroarylamino] and (iv) bicyclic heteroaryl 5/6 or 6/6, bicyclic heteroaryloxy 5/6 or 6/6, heteroaryl-S (O) q-, bicyclic heteroarylamino of 5/6 or 6/6, [and (partially) hydrogenated versions thereof]; wherein q is 0, 1 or 2 and any of the aforementioned ring systems in CYp can be optionally substituted with up to three substituents independently selected from halo, C? _4 alkyl [including geminal disubstitution when CYp is a cycloalkyl or cycloalkenyl ring ], acyl, oxo and nitroC 1-4 alkyl and pharmaceutically acceptable salts thereof. In this embodiment (IP) of the specification the term 'alkyl' includes straight and branched chain structures. For example, C6-6 alkyl includes propyl, isopropyl, and tert-butyl. However, references to individual alkyl groups such as "propyl" are specific for the single straight chained version, and references to branched chain alkyl groups such as "isopropyl" are specific for the single branched chain version. A similar convention applied to other radicals, for example halo (C 4 alkyl) includes 1-bromoethyl and 2-bromoethyl In this embodiment (IP) of the specification of '5- or 6-membered heteroaryl' and 'heteroaryl ring (monocyclic) 'means a 5- or 6-membered aryl ring in which (unless otherwise stated) 1, 2 or 3 ring atoms are selected from nitrogen, oxygen and sulfur. otherwise stated, such rings are fully aromatic.The 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 (IP) of the specification of a '5/6 or 6/6 bicyclic heteroaryl ring system' and 'heteroaryl (bicyclic) ring' means an aromatic bicyclic ring system comprising a ring of 6 members fused to either a 5 ring members or another 6-membered ring, the bicyclic ring system contains 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur. Unless stated otherwise, 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. In this mode (IP) of the specification a '4-, 5- or 6-membered cycloalkyl ring' means a cyclobutyl, cyclopentyl or cyclohexyl ring; and a cycloalkenyl ring of 5- or 6-membered cyclopentyl or cyclohexenyl ring means. The 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 Rllp, R12p, Ri and AR include halo, C? _4 alkyl, hydroxy, nitro, Carbamoyl, -C1-4 alkylcarbamoyl, di- (C 1-4 alkyl) carbamoyl, cyano, trifluoromethyl, trifluoromethoxy, amino, C 1-4 alkylamino, di (C 1-4 alkyl) amino, C 1-4 alkyl S (0) q- (q is 0,16 2), carboxy, C 1-4 alkoxycarbonyl, C 2- alkenyl, C 2- alkynyl, C 1-4 alkanoyl, C 1-4 alkoxy, C 1-4 alkyl (0) ) 2-amino, C1- alkanoylamino, benzoylamino, benzoyl, phenyl (optionally substituted by up to three substituents selected from halo, C1-4 alkoxy or cyano), furan, pyrrole, pyrazole, imidazole, triazole, pyrimidine, pyridazine, pyridine , isoxazole, oxazole, isothiazole, thiazole, thiophene, hydroxyimino-C1-4alkyl, C4-4alkoxyimino-C1-4alkyl, hydroxyC1-4alkyl, haloalkyl of C4-4, nitroalkyl of C1-4, aminoalkyl d e C? _4, C 1-4 cyanoalkyl, C? -4 alkanesulfonamido, aminosulfonyl, C? _4 alkylaminosulfonyl and di- (C 1-4 alkyl) aminosulfonyl. The phenyl and naphthyl groups and the heteroaryl rings (mono- or bicyclic) in Rllp, R1 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 optional substituents particular. For evasion of doubt, the phosphono is -P (O) (0H) 2; C4-4-hydroxy-phosphoryl alkoxy is a monoalkoxy derivative of C4-4 of -O-P (O) (OH) 2; and di-alkoxyphosphoryl of C? _4 is a C 1-4 alkoxy derivative of -O-P (O) (OH) 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. Particular examples of the 5-membered heteroaryl rings contain 2 or 3 heteroatoms independently selected from N, O and S (provided that there are no 0-0, 0-S or SS bonds, and in an alternative embodiment also non-NS links) ) are pyrazole, imidazole, 1,2,3-triazole, 1,2,4-oxadiazole; and also in an alternative embodiment, isothiazole, 1, 2, 5-thiadizole, 1,2,4-thiadiazole or 1, 2, 3-tiadizole. In this embodiment of the formula (IP) a '5/6 or 6/6 bicyclic heteroaryl ring system' and 'heteroaryl (bicyclic) ring' 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 stated otherwise, 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 naphthyl groups and the ring of carbon atoms in the heteroaryl ring (mono or bicyclic) in R14p, R15p, Ri and AR include halo, C? _4 / hydroxy, nitro, carbamoyl, C? _4 alkylcarbamoyl, di- (C1-) alkyl carbamoyl, cyano, trifluoromethyl, trifluoromethoxy, amino, C? -4 alkylamino, di (C1-4 alkyl) amino, alkyl of C 1-4 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 1-4 alkoxy, alkyl of C1-4S (0) 2-amino, C1-4-alkanoylamino, benzoylamino, benzoyl, phenyl (optionally substituted by up to three substituents selected from halo, C4-4 alkoxy or cyano), furan, pyrrole, pyrazole, imidazole , triazole, pyrimidine, pyridazine, pyridine, isoxazole, oxazole, isothiazole, thiazole, thiophene, hydroxyimino-C1-4alkyl, C1-4alkoxyimino-C1-4alkyl, hydroxyC1-4alkyl, C1-4 haloalkyl, C1-4 nitroalkyl, C1-4 aminoalkyl, Ci-4 cyanoalkyl, C1-4 alkanesulfonamido, aminosulfonyl, C1- alkylaminosulfonyl, and di- (C4-4alkyl) aminosulfonyl. The phenyl and naphthyl groups and the heteroaryl rings (mono- or bicyclic) in R1 p, Ri and AR can be mono- or di-substituted in 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, C alquilo _s 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 ?4 alkyl and C1-5 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 1 -4 -alkanoylamino of C 1-4 alkyl include formamidomethyl, acetamidomethyl and acetamidoethyl; examples of C? -4 hidro hydroxyalkyl and C?-6 hydroxyalkyl include hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl and 3-hydroxypropyl; examples of C 1-4 alkoxycarbonyl include methoxycarbonyl, ethoxycarbonyl and propoxycarbonyl; examples of 2- (C 1 -4) alkenyl ethenyl include 2- (methoxycarbonyl) ethenyl and 2- (ethoxycarbonyl) ethenyl; examples of 2-cyano-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 -) ethenyl alkylaminocarbonyl include 2- (methylaminocarbonyl) ethenyl and 2- (ethylaminocarbonyl) ethenyl; examples of 2- (C2-) alkenyl alkyl include allyl and vinyl; examples of alkynyl C2-4 include ethynyl and 2-propynyl; Ci_4 alkanoyl examples include formyl, acetyl and propionyl; examples of C 1 -4 alkoxy include methoxy, ethoxy and propoxy; examples of C? _6 alkoxy and C? _ alco alkoxy include methoxy, ethoxy, propoxy and pentoxy; examples of C1-4 alkylthio include methylthio and ethylthio; examples of C 1-4 alkylamino include methylamino, ethylamino and propylamino; examples of di- (C? _4) amino alkyl 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.sub.1-4-alkoxy dihydroxy of C? _4 and C? -6-alkoxy of C? _6 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 C.sub.44S (0) 2aminQ alkyl include methylsulfonylamino and ethylsulfonylamino; examples of Ci_4 alkanoylamino and C ?_4 alkanoylamino include formamido, acetamido and propionylamino; examples of C4_4 alkoxycarbonylamino include methoxycarbonylamino and ethoxycarbonylamino; Examples N-C 1-4-N-C 1-6 alkanoylamino include N-ethylacetamido, N-ethylacetamido and N-methylpropionamido; examples of C.sub.4-4S (0) pNH- alkyl wherein p is 1 or 2 include methylsulfinylamino, methylsulfonylamino, ethylsulfinylamino and ethylsulphonylamino; examples of C! _4S (O) p alkyl (C? _) N- alkyl wherein p is 1 or 2 include methylsulfinylmethylamino, methylsulfonylmethylamino, 2- (ethylsulfinyl) ethylamino and 2- (ethylsulfonyl) ethylamino; examples of fluoroalkyl of C ?S (0) pNH- wherein p is 1 or 2 include trifluoromethylsulfinylamino and trifluoromethylsulfonylamino; examples of fluoroalkyl of Ci_4S (O) p (Ci_) alkyl NH- wherein p is 1 or 2 includes trifluoromethylsulfinylmethylamino and trifluoromethylsulfonylmethylamino; examples of C 4 -4 (hydroxy) phosphoryl alkoxy include methoxy (hydroxy) phosphoryl and ethoxy (hydroxy) phosphoryl; examples of C? -4 di-alkoxyphosphoryl include di-methoxyphosphoryl, di-ethoxyphosphoryl and ethoxy (methoxy) phosphoryl; examples of C? _4S alkyl (0) q- wherein q is 0, 1 or 2 includes methylthio, ethylthio, methylsulfinyl, ethylsulfinyl, methylsulfonyl and ethylsulphonyl; examples of phenyl S (0) q and naphthyl S (0) q-; wherein q is 0, 1 or 2 are phenylthio, phenylsulfinyl, phenylsulfonyl and nathylthio, naphthylsulfinyl and naphthylsulfonyl respectively; examples of benzyloxy-C 4 alkyl include benzyloxymethyl and benzyloxyethyl; examples of an alkylene chain of C3_4 are trimethylene or tetramethylene; examples of C6-C6 alkyl-C6-alkyl include methoxymethyl, ethoxymethyl and 2-methoxyethyl; examples of C2-6 hydroxy-hydroxy 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 C 2-4 alkoxy include 2-dimethylamino ethoxy and 2-diethylamino ethoxy; examples of phenylalkyl of Cl_4 include benzyl and phenethyl; examples of C 4 alkylcarbamoyl include methylcarbamoyl and ethylcarbamoyl; examples of di (C? _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-alkoxyimino C de4 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 C 4 -4 nitroalkyl include nitromethyl, 1-nitroethyl, 2-nitroethyl and 3-nitropropyl; examples of aminoalkyl of C? _4 include aminomethyl, 1-aminoethyl, 2-aminoethyl, and 3-aminopropyl; examples of the cyanoethyl cyanoethyl, 1-cyanoethyl, 2-cyanoethyl and 3-cyanopropyl; Examples of alkanolamine of C? -4 include methanesulfonamido and ethanesulfonamido; examples of alkylaminosulfonyl of C? _ include methylaminosulfonyl and ethylaminosulfonyl; and examples of C 4 -4 di-alkylaminosulfonyl include dimethylaminosulfonyl, diethylaminosulfonyl and N-methyl-N-ethylaminosulfonyl; examples of C 1-4 alkylsiloxy include methylsulfonyloxy, ethylsulfonyloxy and propylsulfonyloxy; examples of C alca-alkanoyloxy include acetoxy; examples of C4_4 alkylaminocarbonyl include methylaminocarbonyl and ethylaminocarbonyl; examples of di (C? _4) aminocarbonyl alkyl include dimethylaminocarbonyl and diethylaminocarbonyl; examples of C3-.8 cycloalkyl include cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl; examples of C4_7 cycloalkyl include cyclobutyl, cyclopentyl and cyclohexyl; Examples of di (N-C4_4) aminomethylimino alkyl include dimethylamino-methylimino 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 that contain an atom of N and one of S, 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 the ring systems include, for example, indole, benzofuran, benzothiophene, benzimidazole, benzothiazole, benzisothiazole, benzoxazole, benzisoxazole, quinoline, quinoxaline, quinazoline, phthalazine and cinnoline. Other particular examples of AR3 include 5 / 5-, 5/6 and 6/6 bicyclic ring systems containing heterozotomes 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-pyrrole [1,2-a] pyrrole, pyrrole [2, 1-b] thiazole, 1H-imidazo [1, 2-a] pyrrole, 1H-imide -zo [1,2-a] imidazole, 1H, 3H-pyrrole [1, 2-c] oxazole, 1H-imidazo [1, 5-a] pyrrole, pyrrole [1, 2-b] isoxazole, imidazo [5] , 1-b] thiazole, imidazo [2, 1-b] thiazole, indolizine, imidazo [1,2-a] pyridine, imidazo [1,5-a] pyridine, pyrazole [1,5-a] pyridine, pyrrole [1, 2-b] pyridazine, pyrrole [1,2-c] pyrimidine, pyrrolo- [1,2-a] pyrazine, pyrrole [1,2-a] pyrimidine, pyrido [2, 1-c] -s -triazole, s-triazole [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-triazole [4, 3-a] pyrimidine, imidazo [5, lb] oxazole and imidazo [2, 1-b] oxazole. Other specific examples of such ring systems include, for example, 1 [H] -pyrrol [2, 1-c] oxazine, [3 H] -oxazole [3, 4-a] pyridine, [6H] -pyrrole [2, 1-c] oxazine and pyrido [2, 1-c] [1,] oxazine. Other specific examples of the 5/5 bicyclic ring systems are imidazooxazole or idazothiazole, in particular imidazo [5, 1-b] thiazole, imidazo [2, 1-b] thiazole, imidazo [5, lb] oxazole or imidazo [ 2, 1-b] oxazole.

Particular examples of AR3a and AR3b include, for example, indoline, 1, 3, 4, 6, 9, 9a-hexahydropyrid [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-hexahydrooxazole [3, 4a] pyridin-7-yl, (7aS) [3H, 5H] -l, 7a-dihydropyrrole [l, 2c] oxazol-6-yl, (7aS) [5H] -1,2, 3,7a- tetrahydropyrrole [l, 2c] imidazol-6-yl, (7aR) [3 H, 5 H] -1,7a-dihydropyrrole [1,2c] oxazol-6-yl, [3 H, 5 H] -pyrrole [1 , 2-c] oxazol-6-yl, [5H] -2, 3-dihydropyrrole [1, 2-c] i-midazol-6-yl, [3 H, 5 H] -pyrrole [1,2-c] thiazole -6-yl, [3 H, 5 H] -1, 7a-dihydro-pyrrol [1, 2-c] thiazol-6-yl, [5 H] pyrrole [l, 2-c] imidazol-6-yl, [H] ] -3,4,8,8a-tetrahydropyrrole [2, 1-c] oxacin-7-yl, [3 H] -1,5,8,8-tetrahydrooxazsl [3,4-a] pyrid-7-yl, [3 H] -5,8-dihydroxazol [3,4-a] pyrid-7-yl and 5,8-dihydroimidazo [1,5-a] pyrid-7-yl. Particular values for AR4 include, for example, pyrrole [a] quinoline, 2,3-pyrroloisoquinoline, pyrrole [a] isoquinoline, lH-pyrrole [1,2-a] benzimidazole, 9H-imidazo [1, 2-a] indole, 5H-imidazo [2, 1-a] isoindole, 1H-imidazo [3, 4-a] indole, imidazo [1, 2-a] quinoline, imidazo [2, la] isoquinoline, imidazo [1, 5 a] quinoline and imidazo [5, la] isoquinoline. The nomenclature used is that found in, for example, "Heterocyclic Compounds (systems with bridgehead nitrogen), L. 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 established adequate. , the optional substituents for a particular group are those established for similar groups herein. Suitable substituents on AR1, AR2, AR2a, AR2b, AR3, AR3a, AR3b, AR4, AR4a, CY1 and CY2 are (at one 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? -alkoxy 4, alkoxycarbonyl, cyano, nitro, C? -4 alkanoylamino, -CONRvRw or NRvRw} , trifluoromethyl, hydroxy, halo, nitro, cyano, thiol, C? _4 alkoxy, C? _4 alkanoyloxy, dimethylaminomethylaminocarbonyl, di (N-C 1-4 alkyl) aminomethylimino, carboxy, C 1-4 alkoxycarbonyl, C-alkanoyl -4 -4, C? _4S02amino alkyl, C2_4 alkenyl. { optionally substituted by carboxy or C 1-4 alkoxycarbonyl} , C2_4 alkynyl, C? _4 alkanoylamino, oxo (= 0), thioxo (= S), C? _4 alkanoylamino. { the alkanoyl group of C? _ being optionally substituted by hydroxy} , alkyl of C? _ 4S (0) q- (q is O, 1 or 2). { the C?-alkyl group being optionally substituted by one or more groups independently selected from cyano, hydroxy and C? -4 alkoxy} , -CONRvRw or -NRvRw [where Rv is hydrogen or C? _4 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? -4 alkoxy or cyano} , furan, pyrrole, pyrazole, imidazole, triazole, pyrimidine, pyridazine, pyridine, isoxazole, oxazole, isothiazole, thiazole, thiophene, hydroxyimino-C de -4 alkyl, C? -4 alkoxyimino C C -4 alkyl, C halo-haloalkyl, C? -4 alkanesulfonamido, -S02NRvRw [wherein Rv is hydrogen or C? _4 alkyl; Rw is hydrogen or C? _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? - alkyl (including geminal disubstitution), C? _4 alkoxy, C? _4 alkylthio, acetamido, C? _4 alkanoyl, cyano, trifluoromethyl and phenyl]. Preferred optional substituents on CYl & CY2 are mono- or di-substituted by substituents independently selected from C? _4 alkyl (including geminal disubstitution), hydroxy, C? _4 alkoxy, C? _4 alkylthio, acetamido, C? _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) C? _4 alkyl, C? _4 alkanoyl. { wherein the C? -4 alkyl, and C? _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? -4 alkoxy, C? -4 alkoxycarbonyl, C? _4 alkanoylamino, -CONRvRw or -NRvRw [wherein Rv is hydrogen or C? _4 alkyl; Rw is hydrogen or C? _4 alkyl]} , C2-4 alkenyl, C? -4 alkynyl, C? -4 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 the 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. 4_2, 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, T7_, 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 alco _ß alkoxymethyl esters for example methoxymethyl, C? _6 alkanoyloxymethyl esters for example pivaloyloxymethyl, phthalidyl esters, C3_8 cycloalkoxycarbonyloxy esters of C ?_6 alkyl, for example -cyclohexylocarbonyloxyethyl; 1,3-dioxolan-2-onylmethyl esters for example 5-methyl-1,3-dioxolan-2-ylmethyl; and C6-C6 alkoxycarbonyloxyethyl 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 group / major hydroxy groups. Examples of α-acyloxyalkyl ethers include acetoxymethoxy and 2,2-dimethylpropionyloxymethoxy. A selection of the hydrolysable ester in vivo which forms groups by hydroxy includes substituted C? _?, Benzoyl, phenylacetyl, benzoyl and phenylacetyl alkanoyl, C?-Α alkoxycarbonyl or (to give alkylcarbonate esters), di-alkylcarbamoyl C_4 and N- (di-alkylaminoethyl of C? _4) -N-alkylcarbamoyl of C? -4 (to give carbamates), di-alkylaminoacetyl and carboxyacetyl. Examples of substituents on benzoyl include chloromethyl or aminomethyl, C alqu-alkylaminomethyl and di- (C? _4) aminomethyl alkyl, and morpholino or piperazino bonded from a ring of nitrogen atom 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 cyclized prodrugs when the 1,2-diol is on a C? -4 alquilo alkyl chain linked 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 0) of the formula (PD3): ( ?) npd II --P. m * HO / ^ O HO (PD3) Useful intermediates. 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? _4 alkyl (such compounds they are also interesting compounds by themselves), phenyl or phenyl-C de -4 -4alkyl (such phenyl groups optionally substituted by 1 or 2 groups independently selected from C? _4alkyl, nitro, halo and C alco - alkoxy.) Thus, the prodrugs containing the groups such as (PD1), (PD2) and (PD3) can be prepared by the reaction of a compound of formula (I) containing the appropriate hydroxy group (s) with a suitably protected phosphorylating agent (eg, containing a chlorine or dialkylamino leaving group), followed by oxidation (if necessary) and deprotection.When a compound of the formula (I) contains a free hydroxy group number, those groups are not converted into a prodrug functionality that can be protected ( for example, using a t-butyl-dimethylsilyl group), and the last one unprotected.Also, enzymatic methods can be used for selectively phosphorylated or dephosphorylated alcohol functionalities. interesting in vivo oligosables include, for example, those in which Rc was defined by, for example, R14C (O) O-C ?6-C0 alkyl (wherein R14 is, for example, benzyloxy-C de _4 alkyl, or phenyl. Suitable substituents on a phenyl group in such esters include, for example, 4,4-piperazino of C 4 -4 -alkyl-4-alkyl, piperazino-C 4 -alkyl and morpholino-C 4 -alkyl. Where pharmaceutically acceptable salts of an in vivo hydrolysable ester can be formed, this is achieved by conventional techniques. Thus, for example, 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 can forming 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): (?TO) 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 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 have 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 modalities described in the foregoing or the following) are: - (aO) In an HET mode it is a 6-membered heteroaryl as defined in the present, and as defined herein, and in another embodiment, HET is a 5-membered heteroaryl as defined herein. (a) when HET is a 6-membered heteroaryl as defined herein, preferably HET is pyrimidine, pyridazine or pyrazine; more preferably HET is pyrimidin-2-yl, pyridazin-3-yl or pyrazin-2-yl; preferably HET is unsubstituted. (b) When HET is a 5-membered heteroaryl as defined herein, preferably HET is not thiazole; preferably HET is pyrazole, imidazole, oxazole, isoxazole, 1, 2,4-oxadiazole, 1, 2, 5-oxadiazole, 1, 3, 4-oxadiazole, isothiazole, 1,2,3-thiadiazole, 1,2,4-thiadiazole, 1, 2, 5-thiadiazole, 1 , 3,4-thiadiazole, 1, 2, 3-triazole or 1, 2,4-triazole. (c) Even more preferably HET is pyrazol-3-yl, imidazol-2-yl (optionally substituted 3-methyl), imidazol-4-yl (optionally substituted 1-methyl), oxazol-2-yl, isoxazole-3 il, isoxazol-5-yl, 1, 2, 5-oxadiazol-3-yl, 1,2,4-oxadiazol-3-yl, 1, 3, 4-oxadiazol-2-yl, isothiazol-3-yl, isothiazol-5-yl, 1,2,3-thiadiazol-4-yl, 1, 2,4-thiadiazol-3-yl, 1, 2,4-thiadiazol-5-yl, 1, 2, 5-thiadiazol- 3-yl or 1, 3, 4-thiadiazol-2-yl. (d) Further preferred as HET is isoxazol-3-yl, isoxazol-5-yl, 1, 2, 5-oxadiazol-3-yl, 1, 2, 4-oxadiazol-3-yl, 1, 3, 4- oxadiazol-2-yl, isothiazol-3-yl, isothiazol-5-yl, 1,2,3-thiadiazol-4-yl, 1, 2,4-thiadiazol-3-yl, 1, 2,4-thiadiazol- 5-yl, 1, 2, 5-thiadiazol-3-yl or 1,3,4-thiadiazol-2-yl. (e) Particularly preferred as HET is isoxazol-3-yl, isoxazol-5-yl, 1, 2, 5-oxadiazol-3-yl, isothiazol-3-yl, isothiazol-5-yl, 1, 2, 3- thiadiazol-4-yl, 1,2-thiadiazol-3-yl, 1, 2,4-thiadiazol-5-yl, 1, 2, 5-thiadiazol-3-yl or 1,3-thiadiazol-2-yl il. (f) More preferred is HET as isoxazole (optionally substituted as described hereinabove), particularly isoxazol-3-yl. (g) Preferably HET is unsubstituted, (h) Preferably R6p is hydrogen; (i) Preferably Rp and R5p are independently selected from hydrogen, C? _4 alkyl, carboxy, C? _4 alkoxycarbonyl, hydroxymethyl, C? _4 alkoxymethyl or carbamoyl; (j) More preferably R4p and R5p are hydrogen; (k) Preferably R2 and R3 are hydrogen or fluorine; (1) In one aspect of the invention, more preferably one of R and R is hydrogen and the other is fluorine. In another aspect of the invention both of R2 and R3 are fluorine; (m) Preferably > A-B- is of the formula > C = CH- (ie Ra is preferably hydrogen) or > N-CH2-; (n) Preferably D is O or NR7p; (o) Preferably R7'Pp is ARp, R? 1? 0μpC, O, I OP < - R10pCS - (p) More preferably R p is ARp (more preferably benzyl, pyrimidyl, pyridinyl, pyridazinyl or pyrazinyl) or R10pCO-; (q) Particularly R7p is R10pCO-; (ql) Especially preferred is R10pCO- (or R13CO-) wherein R10p (or R13) is alkyl of 1-10 optionally substituted by hydroxy or alkyl of 1-4C S (0) q- (wherein q is 0.1) or 2), wherein the 1-4C alkyl group is optionally substituted as defined herein for this particular substituent; (r) Preferably ARp is 5- or 6-membered heteroaryl; more preferably ARp is 6-membered heteroaryl, such as pyridinyl; (s) Preferred substituents for phenyl and carbon atoms in heteroaryl (mono- and bicyclic) ring systems in ARp, Rllp and R1 include halo, alkyl of 1-4C, hydroxy, nitro, amino, cyano, alkyl 1- 4C (0) p- and 1-4C alkoxy; (t) Preferably the ring systems optionally substituted in ARp, Rllp and R1 are unsubstituted; (u) In another embodiment in the definition of R10p in (PC) mode (IP), 1, 3-dioxolan-4-yl and 1, 4-dioxan-2-yl are excluded. (v) In one aspect of the invention, preferably R10p is 1-4C-alkoxycarbonyl, 1-4C-hydroxyalkyl, 1-4C alkyl (optionally substituted by one or two hydroxy groups, or by an alkanoyl group of 1-4C) , 1-4C-alkylamino, 1-4C-dimethylaminoalkyl, 1-4C-alkoxymethyl, 1-4C-alkanoylmethyl, 1-4C-alkanoyloxy-C 4 -alkyl, 1-5C-alkoxy or 2-cyanoethyl; (w) In one aspect of the invention, more preferably R10p 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; (x) In one aspect of the invention, particularly R 10p is 1,2-dihydroxyethyl, 1,3-dihydroxyprop-2-yl or 1,2,3-trihydroxyprop-1-yl; (y) In another aspect of the invention preferably R10p is hydrogen, alkyl of 1-10C [optionally substituted by one or more hydroxy] or RllpC (O) O-alkyl of 1-6C. (z) In another aspect of the invention, more preferably R10p is hydrogen, hydroxymethyl, 1,2-dihydroxyethyl or acteoxyacetyl; and / or Rc2c is 1-10C alkyl optionally substituted by alkyl of 1-4C S (0) q- (q is 0-2), optionally substituted as in claim 1. (aa) Preferably Rllp is alkyl of 1- 10C; (ab) Preferred optional substituents for 1-10C alkyl in Rllp are hydroxy, cyano, amino, 1-4C alkylamino, 1-4C dialkylamino, 1-4C S (0) p alkyl (wherein p is 1 or 2), carboxy, 1-4C-alkoxycarbonyl, 1-4C-alkoxy, piperazino or morpholino; (ac) Preferred optional substituents for alkyl of 1-6Ca in R12p are hydroxy, alkoxy of 1-4C, cyano, amino, alkylamino of 1-4C, dialkylamino of 1-2C alkyl d 1-4CS (0) P- (in where p is 1 or 2); (ad) Preferably 5 or 6 membered heteroaryl in Rllp is pyridinyl or imidazol-1-yl; (ae) Preferably R12p e-s alkyl of 1-6C; more preferably R12p is tert-butyl or methyl; (af) Preferably R13p is cyano or fluoro; (ag) Preferably R14p is hydrogen; (ah) Preferably CYp is naphthoxy, especially naphth-1-oxo or naphth-2-oxy. Where 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 (thus, for example, Rc and R13 in the formula I) correspond to R7p and R10p in the formula (IP), and similarly for groups D and G). Preferred values of R7p, for example, defined with reference to (IP) are also preferred values of Rc and can be used as preferred values of Rc in any compound of formula (I). For compounds of the formula (I) the preferred values for Rc are those in the group (Rc2) when present in any of the definitions contained in the present Rc - for example when it is present in compounds in which there is a ring system (TC5) or (TC9). The preferred values for R 10p listed in the above for compounds of the formula (IP) are also preferred values for R, 13 in compounds of the formula (I). In the definition of (Rc2c) the AR2a, AR2b, AR3a and AR3b versions of AR2 and AR3 containing the groups are preferably excluded. In another aspect, HET is a 5-membered heteroaryl ring attached to C that contains 2 or 3 heteroatoms independently selected from N, O, and S (with the proviso that there are no 0-0, 0-S, SS, or NS bonds) , in which the ring is optionally substituted on any available C atom (with the proviso that where an N atom is adjacent to the NH linkage, there is no substitution at any C atom that is adjacent to this N atom) by 1 or 2 substituents independently selected from alkyl of 1-4C, amino, alkylamino of 1-4C, alkoxy of 1-4C and halogen, and / or on an available N atom (with the proviso that the ring is not consequently quaternized), by alkyl of 1-4C. In another aspect, HET is selected from the following formulas [HET1) to (HET3): wherein A2 is carbon or nitrogen and B2 is 0, S or N (HET1) (HET2) (HET3) (with a maximum of 3 heteroatoms per ring), with the carbon or nitrogen ring atoms being optionally substituted as described for HET hereinbefore (preferably with no substitution at any carbon atom that is adjacent to the specified N atom) ). The above HET definitions are especially preferred in the (IP) mode. Especially preferred compounds of the present invention are of the formula (IB): wherein HET is isoxazol-3-yl, isoxazol-5-yl, 1,2,4- B) oxadiazol-3-yl, isothiazol-3-yl, 1, 2, 4, -thiazol-3-yl or 1, 2, 5-thiadiazol-3-yl; R2 and R3 are independently hydrogen or fluorine; and Rpl and Rp2 are independently hydrogen, hydroxy, bromine, C? _4 alkyl, carboxy, C? -4 alco alkoxycarbonyl, hydroxymethyl, C? -4 alco 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 isoxazol-3-yl, isoxazol-5-yl, 1, 2, 4-oxadiazol-3-yl, isothiazol-3-yl, I, 2,4-thiadiazol-3-yl or 1,2,5-thiadiazol-3-yl; R2 and RJ 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 in which Rpl and Rp2 are particularly preferred hydrogen. In addition, the especially preferred compounds of the invention are of the formula (IC): ÍIC) wherein HET is isoxazol-3-yl, isoxazol-5-yl, 1,2,4-oxadiazol-3-yl, isothiazole-3 -yl, 1, 2, 4-thiadiazol-3-yl or 1,2,5-thiadiazol-3-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, naphthyl, furan, pyrrole, pyrazole, imidazole, triazole, pyrimidine, pyridazine, pyridine, isoxazole, oxazole, 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-cyanohetenyl, 2-cyano-2- C? -4-ethenyl alkyl or Rep is of the formula R10pCO_, R10pSO2- or R10pCS- (wherein R10p is hydrogen, C? _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? -4 alkylamino, C? _4 alkanoyl, naphthoxy, C2_6 alkanoylamino or C? _4S (0) pNH- alkyl wherein 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, talazine, cinnoline or naphthyridine, or R10p is of the formula RllpC (0) Oalkyl of C? -6 wherein Rllp is C? _6 alkyl, or Rep is of the formula RfC (= 0) C (= 0) - in where Rf is C? _6 alkoxy; or pharmaceutically acceptable salts thereof. Of the above especially preferred compounds of the invention of the formula (IC) those in which HET is isoxazol-3-yl, isoxazol-5-yl, 1, 2, 4-oxadiazol-3-yl, isothiazol-3-yl, 1,2,4-thiadiazol-3-yl or 1,2,5-thiadiazol-3-yl; R2 and R3 are independently hydrogen or fluorine; Rpl and Rp2 are independently hydrogen, AR-oxymethyl or AR-thiomethyl (where AR is phenyl, C? -4 fen phenylalkyl, naphthyl, furan, pyrrole, pyrazole, imidazole, triazole, pyrimidine, pyridazine, pyridine, isoxazole, oxazole, isothiazole , thiazole or thiophene), C? _4 alkyl, carboxy, C? _ alkoxycarbonyl, hydroxymethyl, C? -4 alco alkoxymethyl or carbamoyl and Rep is cyano, pyrimidin-2-yl, 2-cyanohetenyl, 2-cyano-2 -C 4 -4-ethenyl alkyl or Rep is of the formula R 10pCO_, R 10pSO 2 - or R 10pCS- (wherein R 10p is hydrogen, C 1 -C 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? _ alkylamino, C? _4 alkanoyl, naphthoxy, C2-6 alkanoylamino or C? _S alkyl (0) pNH- wherein p is 1 or 2 and q is 0, 1 or 2] pyridine or R10p is of the formula RllpC (O) Oalkyl of C? _6 wherein Rllp is C? _6 alkyl or Rep is of the formula RfC ( = 0) C (= 0) - where Rf is a lcoxy of C? _6; or pharmaceutically acceptable salts thereof are further preferred. Of the above especially preferred compounds of the invention of the formula (IC), particularly the preferred compounds are those wherein HET is isoxazol-3-yl, isoxazol-5-yl, 1,2,4-oxadiazol-3-yl, isothiazol-3-yl, 1,2,4-thiadiazol-3-yl or 1,2,5-thiadiazol-3-yl; R2 and R3 are independently hydrogen or fluorine; Rpl and Rp2 are hydrogen, and Rep is pyridin-2-yl (optionally substituted with cyano) or Rep is of the formula R10pCO- (wherein R 10p is hydrogen, 1,3-dioxolan-4-yl [optionally disubstituted with (C? _4 alkyl or C-5 alkyl [optionally substituted by one or more hydroxy groups] or R10p is of the formula RllpC (O) 0 C? -6 alkyl wherein Rllp is C? _e alkyl); or pharmaceutically acceptable salts thereof. Of the above especially preferred compounds of the invention of the formula (IC), the particularly preferred compounds are those in which Rep is of the formula R10pCO- (wherein R10p 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 particularly preferred compounds of the invention are of the formula (IC) where HET is isoxazol-3-yl; R * and R- are independently hydrogen or fluorine; Rpl and Rp2 are hydrogen, and Rep is R10pCO- (wherein R10p is hydrogen, C5_5alkyl [optionally substituted by one or two hydroxy groups] or R10p is of the formula RllpC (O) 0 C6_6 alkyl at where Rllp is C? _6 alkyl); and pharmaceutically acceptable salts thereof. In another aspect of the invention all of the compounds of the formula (IB) or (IC) described in the above are further preferred when HET is isoxazol-3-yl, isothiazol-3-yl or 1, 2, 5-thiadiazol- 3-ilo. In still another aspect the invention relates to all of the compounds of formula (IB) or (IC) described in the above wherein HET is isoxazol-3-yl or 1,2,4-oxadiazol-3-yl. In still another aspect the invention relates to all of the compounds of the formula (IB) or (IC) described in the above wherein HET is isoxazol-3-yl. In another aspect of the invention, preferred compounds of the formula (IP) are provided wherein HET is isoxazol-3-yl, 1, 2, 4-oxadiazol-3-yl, isothiazol-3-yl, 1, 2, 5- thiadiazol-3-yl; > A-B is > N-CH2- and D is NR7p (or D is O) where Rep is a 6-membered heteroaryl ring containing 1, 2 or 3 nitrogen atoms in the ring as the only heteroatoms in the ring attached via an atom of carbon in the ring and optionally substituted on a carbon atom in the ring by one, two or three substituents independently selected from C? -4 halo, trifluoromethyl, C? -4 S alkyl (0) q- (in where q is 0, 1 or 2), C? _4S (0) 2amino alkyl, C? -4 alkanoylamino, carboxy, hydroxy, amino, C? _4 alkylamino, C? _4 di-alkylamino, C-alkoxycarbonyl ? 4, carbamoyl, C? -4 N-alkylcarbamoyl, di- (C? _4) N-alkyl carbamoyl, C? _4 alkoxy, cyano or nitro, or pharmaceutically acceptable salts thereof. In still another aspect the invention relates to all of the compounds of the formula (IP) immediately described in the above wherein > A-B is > N-CH2- and D is NR7p and where HET is isoxazol-3-yl, isoxazol-5-yl, 1,2,4-oxadiazol-3-yl, isothiazol-3-yl, 1, 2,4-thiadiazole -3-yl ol, 2,5-thiadiazol-3-yl. In all of the above preferred aspects and compounds of formula (IB) or (IC), hydrolysable esters in vivo are preferred where appropriate, esters especially phosphoryl (as defined by formula (PD3) with npd as 1). In all the above definitions, the pharmaceutically active enantiomer compounds (5 (S)). Particular compounds of the present invention include the following: 5 (S) -Isoxazol-3-ylaminomethyl-3- (3-fluoro-4- (3,6-dihydro- (2H) -pyran-4-yl) phenyl) oxazolidin-2-one; 5 (S) -Isoxazol-3-ylaminomethyl-3- (3-fluoro-4-rahorpholinophenyl) -oxazolidin-2-one; 5 (S) -Isoxazol-3-ylaminomethyl-3- [3-fluoro-4- (1-hydroxyacetyl-1, 2,5,6-tetrahydropyrid-4-yl) phenyl] oxazolidin-2-one; 5 (S) -Isoxazol-3-ylaminomethyl-3- [3-fluoro-4- (1- (2 (S), 3-dihydroxypropanoyl) -1,2,5,6-tetrahydropyrid-4-yl) phenyl] oxazolidin-2-one; 5 (S) -Isoxazol-3-ylaminomethyl-3- (3, 5-difluoro-4- (1-hydroxyacetyl-1,2,5,6-tetrahydropyrid-4-yl) phenyl) oxazolidin-2-one; 5 (S) -Isoxazol-3-ylaminomethyl-3- (3, 5-difluoro-4- (1- (2 (S), 3-dihydroxypropanoyl) -1, 2, 5, 6-tetrahydropyrid-4-yl) phenyl] oxazolidin-2-one; 5 (S) -Isoxazol-3-ylaminomethyl-3- (1-hydroxyacetyl-1,2,5,6,6-tetrahydropyrid-4-yl) phenyl] oxazolidin-2-one; 5 (S) -Isoxazol-3-ylaminomethyl-3- (1- (2 (S), 3-dihydroxypropanoyl) -1,2,5,6-tetrahydropyrid-4-yl) phenyl] oxazolidin-2-one; or a pharmaceutically acceptable salt or an in vivo hydrolysable ester thereof. Thus, the Examples more particularly. In this way, the most particularly preferred Examples are Examples Nos. 1, 2, 5, 6, 34, 35, 46 and 48 or pharmaceutically acceptable salts thereof. Particularly preferred salts are the sodium salts. The in vivo hydrolysable esters of Examples 5, 6, 34, 35, 46 and 48 are also preferred, especially phosphoryl esters. 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 such 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 the various general texts on the subject, for example, 'Protective Groups in Organic Synthesis' by Theodora Green (publisher: John Wiley &Sons). The protecting groups may be removed by any convenient 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 being selected as well as affecting the removal of the protective group with alteration. minimum 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 hydroxide O- sodium. 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, for 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 alkylamine, for example, dimethylaminopropylamine 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 above 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. it can be removed, for example, by hydrolysis with a base such as sodium hydroxide, or for example a t-butyl group 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 that can be removed, for example, by hydrogenation on a catalyst such as palladium on carbon. Resins can also be used as a protecting group. 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 (in which, for example, 3, 5-difluorophenyl, 3-fluorophenyl and (de-fluoro) phenyl containing intermediates, all can be prepared by analogous procedures; or by alternative methods - for example, the preparation of (T-group) - (fluoro) phenyl intermediates by reaction of a (fluoro) phenylstannane with, for example, a pyran or (tetrahydro) pyridine compound, can also be prepared by chemical anion (for example WO97 / 30995). Alternatively, the initial materials are necessarily obtainable by procedures analogous to those illustrated which are within the ordinary skill of an organic chemist. Information on the preparation of the necessary initial materials or 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 relevant process sections 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; O99 / 10342; WO99 / 10343; W099 / 11642; European Patent Application Nos. 0,359,418 and 0,609,905; 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 (and 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 US4,476,136); 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. In this manner, 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 (d) as follows (in where the variables are as defined in the foregoing unless stated otherwise): (where the variables are as defined in the foregoing unless stated otherwise): (a) modifying a substituent in or introducing a substituent into other compounds of the formula (I); (b) by the reaction of a compound of the formula (II) O Q- N A O (II) where Y is either (i) hydroxy; or (ii) a dispersible group with a compound of the formula (III): HN (Pg) -HET (III) wherein Pg is a suitable protecting group; or (c) by reacting a compound of the formula (IV): Q-Z (IV) wherein Z is an isocyanate, amine or urethane group with an epoxide of the formula (V): (d) by the reaction of a compound of the formula (II) wherein Y is an amino group with a compound of the formula (IIIA): Lg-HET (IIIA) wherein Lg is a leaving group; and therefore if necessary: (i) eliminate any protective groups; (ii) forming a pharmaceutically acceptable salt; (iii) forming a hydrolysable ester in vivo. Deprotection, salt formation or hydrolysable ester formation in vivo can each be provided as a specific final process step. Where Y is a displaceable group, the values suitable for Y are, for example, a halogen or sulphonyloxy group, for example a chloro, bromo, methanesulphonyloxy or toluene-4-sulfonyloxy group. 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 which describe the preparation of certain suitable starting materials, for example International Patent Application Publication No. WO 97/37980, the contents of which are incorporated herein by reference. Processes analogous to 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, a hydroxy group alkylated to a methoxy group, a hydroxy thio group ethylated to an arylthiomethyl group or a heteroarylthiomethyl group (see, for example, Tet. 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), for example, acylation of a group of the formula (TC5) wherein Rc is hydrogen. (b) (i) Reaction (b) (i) is carried out under Mitsunobu conditions, for example, in the presence of tri-n-butyphosphine and diethyl azodicarboxylate (DEAD) in an organic solvent such as THF, and in the range of temperature of 0 ° C-60 ° C, but preferably at room temperature. Details of the Mitsunobu reactions are contained in Tet.Letts. , 31, 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. Values particularly suitable for Pg are the following, or suitable derivatives thereof; Pg such as to give carbamate (for example Pg as t-BOC or 2,2,2-trichloroethyloxycarbonyl), Pg as C? _4 alkanoyl (for example acetyl or chloroacetyl), phosphoramidate, allyloxy, benzyloxy (and methyl / nitro derivatives) thereof) or sulfonyl (such as, for example, tosylate, mesylate, 4-nitrophenylsulfonyl, 4-methoxy-2,3,6-trimethyl-phenylsulfonyl). See the attached examples for particular values of Pg. Pg could be eliminated by techniques available to the expert chemist (see also the techniques described in the above). For example, tosylate and mesylate can be removed using standard deprotection conditions, or Na / Li or Mg / MeOH amalgam under standard conditions "4-nitrophenylsulfonyl can be removed using a base and phenylthio or thioacetic acid; 4-ethoxy-2, 3 , 6-trimethyl-phenylsulfonyl can be removed using TFA deprotection under standard conditions The compounds of formula (II) wherein Y is hydroxy can be obtained as described in the references cited therein (particularly in the preceding section) the discussion of protecting groups), for example, by reacting a compound of the formula (VI) with a compound of the formula (VII): (SAW) O (VII) wherein R21 is C? -o-benzyl alkyl and R22 is C? -4 alkyl or -S (O) nalkyl of C? -4 where n is 0, 1 or 2. R22 is preferably alkyl of C? _4. In particular, the compounds of formula (II), (VI) and (VII) can be prepared by the skilled chemist, for example, as described in International Patent Application Publication Nos. WO95 / 07271, W097 / 27188 , WO 97/30995, WO98 / 01446 and WO98 / 01446, the contents of which are rporated herein by reference, and by analogous procedures. If no commercially available compound of the formula (III) can be prepared by methods which are selected from the standard chemical techniques, the techniques which are analogous to the synthesis of the known compounds, structurally similar or techniques which are analogous to the described processes in the examples. For example, standard chemical techniques are as described in Houben Weyl, Methoden der Organische Chemie, E8a, Pt. I (1993), 45-225, B. J Wakefield. Many amino-HET compounds are commercially available and can be converted to Hn (Pg) -HET by standard techniques (b) (ii) reactions (b) (ii) are conveniently carried out in the presence of suitable bases such as, for example, a carbonate of alkali metal or alkaline earth metal, alkoxide or hydroxide, for example sodium carbonate or potassium carbonate, or for example an organic amine base such as, for example, pyridine, 2,6-lutidine, collidine, 4-dimethylaminopyridine, tietrilamine, morpholine, or diazabicyclo [5.4.0] undec-7-ene, the reaction is also preferably carried out in a suitable inert solvent or diluent, for example methylene chloride, acetonitrile, tetrahydrofuran, 1,2-dimethoxyethane, N, N-dimethylformamide, N, N-dimethylacetamide, N-methylpyrrolidin-2-one or dimethisulfoxide at and at temperature in the range of 25-60 ° C. When Y is chloro, the compound of the formula (II) can be formed by reacting a compound of the formula (II) wherein Y is hydroxy (hydroxy 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 reacting the hydroxy compound with carbon tetrachloride / triphenyl phosphino in dichloroethane, in a temperature range from 0 ° C to room temperature A compound of the formula (II) wherein Y is chloro or iodo can also be prepared from a compound of the formula (II) wherein Y 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. And it is C C _4 alkanesulfonyloxy or tosylate, the compound (II) can be prepared by reacting the hydroxy compound with C1- alkanesulfonyl chloride or tosyl chloride in the presence of a ba be gentle such as triethylamine or pyridine. When Y is a phosphoryl ester (such as Ph02-P (0) -O) or Ph2-P (0) -0- the compound (II) can be prepared from the hydroxy compound under standard conditions. (c) Reaction (c) was performed under conditions analogous to those described in the following references which describe as analogous and suitable starting materials can be obtained. Reaction (c) is especially suitable for compounds in which HET is an electron deficient ether (such as, for example, thiadiazole or triazine). The compounds of the formula Q-Z wherein Z 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 J. Med. Chem. 1990, 33, 25"69-2578 and Chung-Ho Park et al in J. Med. Chem. 1992, 35, 1156-1165 The compounds of the formula QZ is where Z is a urethane 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 (c) can be performed in which QZ where Z is an amine group reacted with the epoxide (optionally in the presence of an organic base), and the product was 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 reactions and analogous preparations. The epoxides of the formula (V) can be prepared from the corresponding compound of the formula (VIII): (VIII) Certain intermediate epoxide and alkane are novel and are provided as a further feature of the invention. For example, when T or T is isoxazol-3-yl, 3- (2, 3-oxiranopropylamino) isoxazole can be prepared from 3-allylaminoisoxazole. The asymmetric epoxidation can be used to give the desired optical isomer. (d) The skilled artisan will appreciate that for the reaction of a compound of the formula (II) wherein Y is an amino group with a compound of the formula (III), Lg-HET, certain heteroethyls reactive HET reacts satisfactorily, such as triazines and pyridazines. A suitable value for Lg is chlorine. The reaction is carried out under standard conditions in an inert solvent and in the presence of a suitable base (such as triethylamine). The compounds of the formula (II) wherein Y is amino can be obtained as described in the references cited therein (particularly in the section proceeding the discussion of protecting groups) for example of the corresponding compounds in which Y it is hydroxy (through azide). 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 ability 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 it occurs). 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 treating 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 a treatment, which comprises administering to the animal a. effective amount of a compound of the present 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 acceptable salt of a hydrolysable ester in vivo, (hereinafter in this section relates to the pharmaceutical composition "a compound of this invention") for the therapeutic (including prophylactic) treatment 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), an in vivo hydrolysable ester 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 carbapenem, for example meropene or imipenem, to extend the therapeutic effectiveness. The compounds of this invention may also contain or be co-administered with products of increased permeability / bactericidal permeability proteins or spill pump inhibitors (BPIs) to improve the activity against the gram-negative bacteria resistant to bacterial antibacterial 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- to 20 mgkg-1 of a compound of this invention, the composition being administered 1 to 4 times per day. In another embodiment a daily dose of 5 mgkg-1 to 20 mgkg "1 of the compound of this invention is administered.Intravenous, subcutaneous and intramuscular dose can be given by means of a ball injection.Alternatively the intravenous dose can be given. by continuous infusion over a period of time.

Alternatively, each patient may receive a daily oral dose which may be approximately equivalent to the daily parenteral dose, the composition being administered 1 to 4 times per day. A pharmaceutical composition to be intravenously dosed may advantageously contain (for example in increased stability) a suitable bactericidal, antioxidant or reducing agent, or a suitable sequestering agent. In the foregoing, other features of prior pharmaceutical compositions, process, method, use and manufacture of medicament, also apply alternatives and preferred embodiments of the compounds of the invention described herein are also applied. Antibacterial Activity: The pharmaceutically acceptable compounds of the present invention are useful antibacterial agents having a good spectrum of activity in vitro against gram standard positive organisms, which are useful for screening, - for activity against pathogenic bacteria. Notably, the pharmaceutically acceptable compounds of the present invention show activity against enterococci, pneumococci and strains resistant to methicillin of S. aureus and staphylococcus negative of caagulase. The antibacterial spectrum and the potency of a particular compound can be determined in a standard test system. The (antibacterial) 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 terms of the minimum inhibitory concentration (MIC) determined by the agar-dilution 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 for 24 hours - standard test conditions for the expression of methicillin resistance. Streptococcus and enterococcus 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. For example, the following results were obtained by the compound of Example 2.

Organism MIC (μ / ml) Staphylococcus eureus: Oxford 0.5 Novb. Res 1 MRQR 1 Staphylococcus Negative to Coagulase MS 0.5 MR 1 Streptococcus pyogenic C203 1 Enterococcus faecalis 2 Bacillus subtilis 0.5 Novb. Res = Novobiocin resistant MRQR = methicillin resistant quinolone resistant MR = methicillin resistant MS = sensitive methicillin Certain intermediates and / or Reference Examples described hereafter (especially those in which the -NH to HET linkage is produced by a BOC group) they may also possess useful activity and are provided as a further feature of the invention. The invention is now illustrated but not limited by the following Examples in which unless stated otherwise:. (i) The evaporations are carried out by rotary evaporation in vacuo and the working procedures are carried out after the removal of the residual solids by filtration. (ii) operations are carried out at room temperature, which is typically in the range of 18-26 ° C and in air unless otherwise stated, or at least the expert could work otherwise 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 a 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 internal standard multiplicities (d scale) and peak are shown as follows: 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 electroaspersion and, where appropriate, either positive ion data or negative ion data were collected]; (vi) the intermediates are not generally and completely characterized and the purity was in general evaluation by thin-layer chromatography, infrared (IR), spectral mass (MS) or NMR analysis; and (vii) in which the following abbreviations may be used: © is a trademark; DMF is N, N-di ethylfomamide; DMA is N, N-dimethylacetamide; TLC is thin layer chromatography; HPLC is high pressure liquid chromatography; MPLC is medium pressure liquid chromatography; DMSO is dimethyl sulfoxide; CDC13 is deuterated chloroform; MS is 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.

Example 1: 5- (S) -Isoxazol-3-ylaminomethyl-3- (3-fluoro-4- (3,6-dihydro- (2H) -pyran-4-yl) enyl) oxazolidin-2-one To a stirred solution of 3- (2,2,2-tichloroethyloxycarbonylamino) isoxazole (631 mg, 2.43 mmol) in dry N, N-dimethylformamide (10 ml), under a nitrogen atmosphere was added a suspension of sodium hydride ( 107 mg of a 60% dispersion in oil, 2.67 mmol) in hexane followed by 5 (R) -methanesulfonyloxymethyl-3- (3-fluoro-4- (3,6-dihydro- (2H-pyran-4-yl) phenyl) oxazolidin-2-one (see WO 97/0928; 226 mg, 0.61 mmol) in dry DMF (3 ml). Over a period of 24 hours, additional batches of sodium hydride were added in total (428 mg dispersion at 60 ° C). % in oil, 10.7 mmol) and the reaction mixture was heated at 50-60 ° C for 24 hours, after which time the TLC indicated the formation of the desired product (Rf 0.34, 50%, ethyl acetate / hexane). The majority of the N, N-dimethylformamide was evaporated under high vacuum and the product was isolated by MPLC (50% THF / Hexane) and then triturated with ether to yield the title compound as a solid. White fo (63.4 mg, 29%). NMR: 2.42 (m, 2H), 3.45 (m, 2H), 3.81 (m, 3H), 4.15 (t, ÍH), 4.21 (d, 2H), 4.90 (m, ÍH), 6.01 (d, ÍH) , 6.09 (m, ÍH), 6.53 (t, ÍH), 7.31 (dd, ÍH), 7.40 (t, ÍH), 7.48 (dd, ÍH), 8.39 (d, ÍH); m / z: ES + (M + H) = 360. The starting material 3- (2,2,2-trichloroethyloxycarbonylamino) isoxazole (Reference Example 1) was prepared as follows: To a solution of 3-aminoisoxaxol (2.0 g) , 23.8 mmoles) and sodium acid carbonate (5.0 g, 59.5 mmoles) in acetone / water (45 ml, 2: 1), at 0-5 ° C, 2, 2, 2-trichloroethyl chloroformate was added dropwise ( 5.5 g, 26.2 mmol, 3.6 ml) in acetone (15 ml). The reaction mixture was allowed to warm to room temperature and was stirred for 4 hours. The back was then cooled to 0-5 ° C and an additional portion of sodium acid carbonate (5.0 g, 59.5 mmol), and 2,2,2-trichloroethyl chloroformate (5.55 g, 26.2 mmol, 3.6 ml) in acetone (10 ml) was added. The solution was allowed to warm to room temperature and stirred for an additional 3 hours. The solution was allowed to warm to room and was stirred for an additional 3 hours. Thin layer chromatography after this time showed complete reaction (Rf = 0.79, 5% MeOH / CH 2 Cl 2). Water was added and the mixture was taken up in ethyl acetate (4x), and the extracts were combined, washed with brine, dried over sodium sulfate, and concentrated by rotary evaporation to give a yellow oil (112 g). This was purified by MPLC (3% MeOH / CH2Cl2) and recrystallized from cyclohexane to give the title compound as white fluffy crystals. (4.91 g, 80%). NMR: 4.95, (s, 2H), 6.74 (d, ÍH), 8.78 (d, ÍH), 11.19 (s H); m / z: ES + (M + H) = 259. Example 2j 5 (S) -Isoxazol-3-ylaminomethyl-3- (3-fluoro-4-morpholinophenyl) -oxazolidin-2-one To a stirred solution of 5 ( R) - [N- (2, 2, 2-trichloroethyloxycarbonyl) aminomethyl] -3- (3-fluoro-4-morpholinophenyl) oxazolidin-2-one (140 mg, 0.26 mmol) in glacial acetic acid (6 ml) a room temperature under nitrogen atmosphere, zinc powder was added (acid was washed, 68 mg, 1.04 mmol). After 4 hours an additional portion of zinc (68 mg, 1.04 mmol) was added and stirring was continued for an additional 1.5 hours until the reaction was complete. The reaction mixture was filtered and concentrated by rotary evaporation to give colorless crystals (347 mg) which were recovered in dichloromethane (2x), with sonication. The resulting suspension was filtered and chromatographed by MPLC (3% MeOH / CH2Cl2), and additional MPLC (40-80% ethyl acetate / hexane gradient). The title compound was isolated as an amorphous solid by trituration of the concentrated fractions with ether (23.4 mg, 25%) NMR: 2.94 (t, 4H), 3.41 (t, 2H), 3.71 (m, 4H), 3.77 ( t, ÍH), 4.10 (t ÍH), 5.98 (s, 1H), 6.50 (t, ÍH), 7.04 (t, ÍH), 7.17 (d, ÍH), 7.48 (dd, ÍH), 8.37 (s, ÍH). MS: ES + (M + H) = 363. The starting material 5- (R) - [N-Isoxazol-3-yl-N- (2,2,2-tichloroethyloxycarbonyl) aminomethyl] -3- (3 -fluoro-4-morpholinophenyl) oxazolidin-2-one (Reference Example 2) as follows: To a stirred solution of 3- (2,2,2-trichloroethoxyloxycarbonylamino) isoxazole (260 mg, 1.0 mmol), 5 (R) -hydroxymethyl-3- (3-fluoro-4-morpholinophenyl) oxazolidin-2-one (see WO 95/07271; 93 mg, 1 mmol), and tributylphosphine (303 mg, 1.5 mmol) in dry tetrahydrofuran (10 ml) at 0 ° C under a nitrogen atmosphere, was added 1,1'- (azodicarbonyl) dipiperidine (378.5 mg, 1.5 mmol) in dry tetrahydrofuran (3 ml). The reaction was allowed to warm to room temperature and stirred for 4 days during which time a white suspension formed. The reaction mixture was filtered and the residue was washed with tetrahydrofuran. The filtrate was concentrated by rotary evaporation to give a yellow oil (1.2 g) which was purified by MPLC (30% ethyl acetate / hexane, ICN N 32-63 alumina), and additional MPLC (100% CH2C12, alumina ICN N 32-63). Concentration of the fractions by rotary evaporation gave the title compound as a crisp white foam (296 mg, 55%). NMR: 2.97 (t, 4H), 3.73 (t, 4H), 3.88 (m, ÍH), 4.17 (m, 2H), 4.38 (m, ÍH), 5.04 (m, 3H), 6.90 (s, 1H) , 7.06 (t, ÍH), 7.18 (dd, ÍH), 7.46 (dd, 1H), 8.91 (d, ÍH); m / z ES + (M + H) = 537. Example 3: 5 (S) -l3? Xazol-3-ylaminomethyl-3- (3-fluoro-4- (1-ormyl-1, 2,5,6-tetrahydropyrid-4-) il) phenyl) oxazolidin-2-one To a stirred solution of 5 (R) - [N-isoxazol-3-yl-N- (2,2,2-trichloroethyloxycarbonyl) -aminomethyl] -3- [3-fluoro-4- (1-formyl-1, 2, 5, 6-tetrahydropyrid-4-yl) phenyl] oxazolidin-2-one (110 mg, 0.2 mM) in acetic acid (3 ml) was added zinc powder (130 mg, 2.0 mM). The mixture was kept in an ultrasonic bath for 10 minutes, and then vigorously stirred for 48 hours under a nitrogen atmosphere at room temperature. The mixture was filtered through celite and the filtrate was evaporated. The residue was taken up in -5% MeOH / CH 2 Cl 2 (5 ml) with filtration of inorganic material and the title compound was isolated by MPLC (4% 'MeOH / CH 2 Cl 2). This was obtained as a brittle glass on evaporation under high vacuum (22 mg, 28%). NMR: 2.41 (s, 2H), 3.45 (m, 2H), 3.60 (m, 2H), 3.84 (t, ÍH), 4.08 (m, 2H), 4.19 (t, ÍH), 4.91 (m, 1H) , 6.00 (m, 2H), 6.53 (m, ÍH), 7.36 (m, 2H), 7.54 (d, 2H), 8.11 & 8.19 (2s, 1H), 8.37 (s, ÍH); m / z ES + (M + H) = 387. The starting material 5 (R) - [N-Isoxazol-3-ylN- (2,2,2-trichloroethyloxycarbonyl) aminomethyl] -3- [3-fluoro] was obtained. -4- (1-formyl-1, 2, 5, 6-tetrahydropyrid-4-yl) phenyl] oxazolidin-2-one (Reference Example 5) as follows: 5 (R) - [N-Isoxazole-3-] il-N- (2,2,2-trichloroethyloxycarbonyl) aminomethyl] -3- [3-fluoro-4- (1-benzyl-1,2,5,6-tetrahydropyrid-4-yl) phenyl] oxazolidin-2- ona (Reference Example 3) To a stirred solution of 3- (2,2,2-trichloroethyloxycarbonylamino) isoxazole (1.30 g, 5.0 mmol), 5 (R) -hydroxymethyl-3- (3-fluoro-4- (1 -benzyl-l, 2, 5, 6-tetxahydropyrid-4-yl) phenyl) oxazoldin-2-one (WO 97/30995; 1.91 g, 5.0 mmol) and tributylphosphine (1.52 g, 7.5 mmol) in dry tetrahydrofuran (50 ml) under a nitrogen atmosphere at 0 ° C, added 1, 1 '- (azodicarbonyl) dipiperidine (1.89 g, 7.5 mmol) in dry tetrahydrofuran (15 ml). The solution was stirred at 0 ° C for 30 minutes before being allowed to reach room temperature and this was then stirred for 2 days. The mixture was filtered, concentrated by rotary evaporation and chromatographed by MPLC (30% ethyl acetate / hexane, ICN Alumina N 32-63), and triturated with ether to give the title compound as a white amorphous solid ( 1.62 g, 52%) NMR: 2.41 (m, 2H), 2.60 (t, 2H), 3.15 (m, 2H), 3.90 (dd, ÍH), 4.18 (m, 2H), 4.37 (dd, ÍH), 5.04 (dd, 3H), 5.95 (s broad, ÍH), 6.88 (s, ÍH), 7.32 (m, 3H), 8.89 (s, 1H); m / z ES + (M + H) = 623. 5 (R) - [N-Isoxazol-3-yl-N- (2,2,2-trichloroethyloxycarbonyl) aminomethyl] -3- [3-fluoro-4- ( 1,2,5,6-tetrahydropyrid-4-yl) phenyl] oxazolidin-2-one (Reference Example 4) To an ice-cooled stirred solution of 5 (R) - [N-isoxazol-3-yl-N] - (2,2,2-trichloroethyloxycarbonyl) aminomethyl] -3- [3-fluoro-4- (1-benzyl-1,2,5,6-tetrahydropyrid-4-yl) phenyl] oxazolidin-2-one (720 mg, 1.15 mmol) and N, N-diisopropylethylamine (44.8 mg, 0.34 mmol, 60 μl) in dichloromethane (40 ml) under a nitrogen atmosphere was added dropwise 1-chloroethyl chloroformate (214 mg, 1.5 mmol, 162 μl). The reaction mixture was allowed to warm to room temperature and after 30 minutes the reaction was complete. This was chromatographed by MPLC (40% ethyl acetate / hexane) to yield a clear oil (737 mg) which was dissolved in methanol and stirred at 60 ° C, for 20 minutes, before the solvent was removed by rotary evaporation. to give the title compound as an amorphous solid (538 mg, 94%). NMR: 2.71 (m, 2H), 3.35 (m, 2H), 3.80 (m, 2H), 4.00 (m, ÍH), 4.27 (m, 2H), 4.45 (dd, ÍH), 5.13 (m, 3H) , 6.10 (, ÍH), 6.96 (s, ÍH), 7.38-7.60 (m, 3H), 9.00 (s, ÍH), 9.21 (s broad, 2H); m / z ES + (M + H) = 533. 5 (R) - [N-Isoxazol-3-yl-N- (2,2,2-trichloroethyloxycarbonyl) aminomethyl] -3- [3-fluoro-4- ( 1-formyl-1, 2, 5, 6-tetrahydropyrid-4-yl) phenyl] oxazolidin-2-one (Reference Example 5) To a suspension of 5 (R) - [N-isoxazol-3-yl-N - (2,2,2-trichloroethyloxycarbonyl) aminomethyl] -3- [3-fluoro-4- (1,2,5,6-tetrahydropyrid-4-yl) phenyl] oxazolidin-2-one (100 mg, 0.175 mmol in ethyl formate (5 ml), with stirring was added, triethylamine (20 mg, 27 μl, 0.2 mmol), and the mixture was heated to reflux overnight Ethyl formate was added and the mixture was washed with 2M hydrochloric acid and saturated brine, dried over sodium sulfate and concentrated by rotary evaporation to give the crude title compound as a yellow gum (115 mg, 117%). M / z ES + (M + H) = 561. Example 4: 5 (S) -Isoxazol-3-ylaminomethyl-3- [3-luoro-4- (1-acetoxyacetyl-1, 2,5,6-tetrahydropyrid-4-yl) enyl] oxazolidin-2- ona To a stirred solution of 5 (R) - [NI soxazol-3-yl-N- (2,2, 2-trichloroethyloxycarbonyl) aminomethyl] -3- [3-fluoro-4- (1-acetoxyacetyl-1, 2,5,6-tetrahydropyrid-4-yl) phenyl] oxazolidin-2-one (1.14 g, 1.8 mM) in acetic acid (15 ml) was added zinc powder (1.17 g, 18 mM). The mixture was placed in an ultrasonic bath for 10 minutes, then water (2 ml) was added and the mixture was stirred vigorously for 24 hours under nitrogen at room temperature. The mixture was filtered through celite and the filtrate was evaporated. The title compound was isolated by MPLC (4% MeOH / CH2Cl2). This was obtained as a crystalline solid in trituration with ether (473 mg, 57%). NMR: 2.10 (s, 3H), 2.42 (s, 2H), 3c45 (t, 2H), 3.58 (t, ÍH), 3.67 (t, ÍH), 3.85 (d of d, ÍH), 4.09 (s, 2H), 4.18 (t, ÍH), 4.86 (m, 3H), 6.00 (d, 2H), 6.52 (t, 1H), 7.29 (d of d, ÍH), 7.38 (tIH), 7.50 (d, ÍH), 8.38 (s, ÍH); m / z ES + (+ H) 459. The starting material 5 (R) - [N-Isoxazol-3-yl (2,2,2-trichloroethyloxycarbonyl) aminomethyl] -3- [3-fluoro-4- was prepared (l-Acetoxyacetyl-1,2,5,6-tetrahydropyrid-4-yl) phenyl] oxazolidin-2-one (Reference Example 6) _ as follows: To a stirred solution, cooled in ice of 5 (R) - [N-isoxazole-yl-N- (2,2,2-trichloroethyloxycarbonyl) aminomethyl] -3- [3-fluoro-4- (1,2,5,6-tetrahydropyrid-4-yl) phenyl] oxazolidin-2 -one (102 mg, 0.18 mmol) and sodium bicarbonate (75 mg, 0.89 mmol) in acetone (10 ml) / water (5 ml), acetoxyacetyl chloride (49 mg, 0.36 mmol, 38.5 μl) was added dropwise. . After 15 minutes, the complete reaction occurred by TLC (10% MeOH / CH2Cl2, UV visualization, Rf = 0.75). Water was then added and the aqueous phase was taken up in ethyl acetate, the resulting organic phase was washed with water, 2M hydrochloric acid, and saturated brine, dried over magnesium sulfate and concentrated by rotary evaporation to give the title compound as an unpurified yellow gum (105 mg, 93%). NMR: 2.10 (broad s, 3H), 2.42 (m, 2H), 3.62 (dt, 2H), 3.94 (m, 1H), 4.19 (m, 4H), 4.40 (dd, ÍH), 4.84 (d, 2H) ), 5.05 (m, 3H), 6.01 (s broad, ÍH), 6.91 (s, ÍH), 7.31 (d, ÍH), 7.43 (m, 2H), 8.91 (s, ÍH); m / z: ES + (M + H) = 633. Example 5: 5 (S) -Isoxazol-3-ylaminomethyl-3- [3-luoro-4- (1-hydroxyacetyl-1, 2,5,6-tetrahydropyrid -4-yl) phenyl] oxazolidin-2-one A solution of 5 (S) -Isoxazol-3-ylaminomethyl-3- [3-fluoro-4- (l-acetoxyacetyl-1) was stirred for 18 hours at room temperature. 2,5,6-tetrahydropyrid-4-yl) phenyl] oxazolidin-2-one (400 mg, 0.87 mM) in saturated methanolic ammonia (10 ml). The title compound was crystallized by evaporating to a small volume and triturated with ether (334 mg, 92%). NMR: 2.45 (s, 2H), 3.46 (t 2H), 3.69 (t, ÍH), 3.84 (d of ÍH), 4.12 (m, 5H), 4.55 (m, ÍH), 4.90 (6 line, ÍH) , 6.00 (m, 2H), 6.54 (t, 1H), 7.31 (d of d, 1H), 7.37 (t, ÍH), 7.51 (d, ÍH), 8.38 (s, ÍH); m / z ES + (M + H) 417. Example 6: 5 (S) -Isoxazol-3-ylaminomethyl-3- [3-luoro-4- (1- (2- (S), 3-dihydroxypropanoyl) -1 , 2,5,6-tetrahydropyrid-4-yl) enyl] oxazolidin-2-one To a stirred solution of 5 (R) - [N-isoxazol-3-yl-N- (2, 2, 2-trichloroethyloxycarbonyl) aminomethyl] -3-. { 3-fluoro-4- [N- (2, 2-dimethyl-1,3-dioxolan-4 (S) -ylcarbonyl) -1,2,5,6-tetrahydropyrid-4-yl] phenyl} Oxazolidin-2-one (200 mg, 0.3 mM) in acetic acid (3 ml) was added zinc powder (195 mg, 3.0 mM). The mixture was placed in an ultrasonic bath for 10 minutes, then vigorously stirred for 24 hours under a nitrogen atmosphere at room temperature. Water (0.5 ml) was added and stirring was continued for an additional 24 hours. The reaction mixture was filtered through celite and evaporated. The residue was dissolved in tetrahydrofuran (15 ml) / 1.0 M aqueous HCl (10 ml) and stirred at room temperature for 3 days. This was evaporated to dryness and the residue was chromatographed by MPLC (8% MeOH / CH2Cl2, gradient at 25%). The title compound was obtained as a white powder in trituration with ether / ethanol (68 mg, 50%). NMR: d 2.42 (s, 2H, partially obscured), 3.43 (m, 2H), 3.57 (m, ÍH), 3.79 (m, 3H), 4.16 (m, 2H), 4.27 (m, ÍH), 4.38 (m, ÍH), 4.72 (m, ÍH), 4.91 (m, ÍH), 5.00 (m, ÍH), 6. 00 (m, 2H), 6.57 (t, ÍH), 7.30 (d of d, ÍH), 7.39 (t, ÍH), 7. 50 (d of d, ÍH), 8.40 (s, ÍH); m / z ES + (M + H) = 447. The starting material 5 (R) - [N-isoxazol-3-yl-N- (2,2,2-tricyloxyethyloxycarbonyl) aminomethyl] -3- was prepared. { 3-fluoro-4- [N- (2, 2-dimethyl-1,3-dioxolan-4 (S) -ylcarbonyl) -1,2,5,6-tetrahydropyrid-4-yl] phenyl} oxazolidin-2-one (Example of Reference 7) as follows: To a stirred solution of 5 (R) - [N-isoxazol-3-yl-N- (2,2,2-trichloroethyloxycarbonyl) -aminomethyl] -3- [3-fluoro-4- ( 1, 2, 5, 6-tetrahydropiid-4-yl) phenyl] oxazolidin-2-one (228 mg, 0. 4 mM) in dry dichloromethane (5 ml) at 0-4 ° C, pyridine (158 mg, 2.0 mM) was added followed by dropwise addition of a solution of (S) - (+) -2,3 chloride, 0-isopropylidene glycine (EP 0 413 401 A2; 200 mg, 1.2 mM) in dichloromethane (1 ml). The solution was stirred at 0-4 ° C for 10 minutes, and then allowed to warm to room temperature. The reaction mixture was washed with water and brine, dried over sodium sulfate and evaporated to a gum. The title compound was isolated by MPLC (60% ethyl acetate / isohexane) and obtained as a crisp foam on evaporation (158 mg, 60%). NMR: 1.36 (m, 6H), 2.42 (s, 2H), 3.79 (m, 2H), 3.92 (m, ÍH), 4.15 (m, 6H), 4.40 (d of d, ÍH), 4.90 ( 5 line, ÍH), . 05 (4 line, 3H), 6.03 (s, ÍH), 6.90 (s, ÍH), 7.25-7.50 (m, 3H), 8.91 (s, ÍH); m / z: ES + (M + H) = 661. Example 7: 5 (S) -Isoxazol-3-ylaminomethyl-3- (4-imidazol-1-yl-3-luoro-enyl) -oxazolidin-2-one, 5 (R) - (N- (2,2,2-trichloroethyloxycarbonyl) -isoxazol-3-ylaminomethyl) -3- (4-imidazol-1-yl-3-fluorophenyl) oxazolidin-2-one (without purifying 1.7 g, ~ 2.5 mM), was stirred in a mixture of acetic acid (40 ml) and water (18 ml) under nitrogen at room temperature. Zinc powder (824 m, 12.5 mM) was added, the mixture was stirred 20 minutes, an additional portion (200 mg) of zinc was added, and stirring was continued for 1 hour. The mixture was filtered through celite, and the filter pad was well washed with a mixture of acetic acid and water (5: 1). The filtrates were evaporated, and the residue was partitioned between hydrochloric acid (0.5 M, 200 ml) and dichloromethane (150 ml). The aqueous phase was washed with dichloromethane (100 ml), then made basic with the minimum amount of concentrated ammonia solution, reextracted with dichloromethane (2 x 150 ml), dried (magnesium sulfate), and evaporated. Recrystallization from isopropanol (40 ml) gave the desired product (470 mg). NMR (DMSO-de) d: 3.46 (t, 2H); 3.87 (dd, ÍH); 4.21 (t, 1H); 4.92 (m, ÍH); 6.01 (d, ÍH); 6.53 (t, ÍH); 7.12 (t, ÍH); 7.46 (dd, ÍH); 7.53 (d, ÍH); 7.66 (t, 1H); 7.74 (dd, 1H); 7.98 (m, ÍH); 8.39 (d, ÍH). MS (ESP): 362 (MH +) for C 16 H 4 FN 503 The 5 (R) - (N- (2,2,2-Trichloroethyloxycarbonyl) -isoxazol-3-ylaminomethyl) -3- (4-imidazole-1) was prepared. intermediary il-3-fluorophenyl) oazolidin-2-one as follows: 3- (4-Imidazol-1-yl-3-fluorophenyl) -5 (R) -hydroxymethyloxazolidin-2-one (693 mg, 2.5 mM, see WO 96-23788) and 3- (2, 2, 2) were suspended. -trichloroethyloxycarbonylamino) isoxazole (649 mg, 2.5 mM) was stirred in dry tetrahydrofuran (25 ml) under nitrogen in an ice bath. Tributylphosphine (808 mg, 4 mM) was added followed by 1,1'- (azodicarbonyl) dipiperidine (945 mg, 3.75 mM) dissolved in tetrahydrofuran (10 ml) for 10 minutes. The mixture was then stirred 18 hours, allowing room temperature to rise, then filtered, and the filter cake was washed with tetrahydrofuran. The combined filtrates were evaporated and the residue was purified by chromatography on a 20 g Mega Bond Elut® silica column, eluting with a gradient increasing in polarity from 0 to 5% methanol in dichloromethane. The relevant fractions were combined, evaporated, and the residue was triturated with diethylether to give the desired product (1.36 g), contaminated with tributylphosphine oxide. NMR (DMS0-d6) d: 3.95 (dd, ÍH); 4.16 (dd, ÍH); 4.26 (t, ÍH); 4.41 (dd, ÍH); 4.99 (d, ÍH); 6.08 (dd overlapping m, 2H); 6.89 (d, 1H); 7.10 (t, ÍH); 7.44 (dd, ÍH); 7.52 (d, ÍH); 7.66 (t, ÍH); 7.71 (dd, ÍH); 7.98 (m, ÍH); 8.90 (d, ÍH). MS (ESP): 518 (MH +) for C? 6H? 4FN503 Example 8 5 (S) -Isoxazol-3-ylaminomethyl-3- (4- (4-hydroxymethylimidazol-1-yl) -3-luoofenyl) oxazolidin- 2-one 3- (4- (4-Hydroxymethylimidazol-1-yl) -3-fluorophenyl) -5 (R) - (N- (t-butoxycarbonyl) isoxazol-3-ylaminomethyl) oxazolidin-2-one was dissolved ( 360 mg, 0.76 M) in dichloromethane (10 ml) and treated with trifluoroacetic acid (10 ml). After stirring for 30 minutes the solvent was evaporated, the residue was repeatedly evaporated to dryness with dichloromethane (3 x 10 ml), and the resulting gum was dissolved in water (10 ml). The solution was made basic with concentrated aqueous ammonia, and the resulting precipitate was filtered, washed with water and dried to give the title product (190 mg). MS (ESP): 374 (MH +) for C? 7H? 6F? 503? MR (DMSO-ds) d: 3.45 (t, 2H); 3.85 (dd, ÍH); 4.19 (t, ÍH); 4.39 (d, 2H); 4.88 (t, ÍH); 4.95 (m, ÍH); 5.99 (d, 1H); 6.53 (t, ÍH); 7.31 (d, ÍH); 7.43 (dd, ÍH); 7.62 (t, ÍH); 7.72 (dd, ÍH); 7.90 (d, ÍH); 8.36 (d, ÍH). The intermediate 3- (4- (4-hydroxymethylimidazol-1-yl) -3-fluorophenyl-5 (R) - (N- (t-butoxycarbonyl) -isozol-3-ylaminomethyl) oxazolidin-2-one was prepared as follows: 3- (4- (4-t-Butyldimethylsilyloxymethylimidazol-1-yl) -3-fluorophenyl) -5 (R) -hydroxy-methyloxazolidin-2-one (842 mg, 2 M, see WO 97-31917) was suspended. ) and 3- (t-butoxycarbonyl-amino) isoxazole (405 mg, 2.2 mM) was stirred in dry tetrahydrofuran (15 ml) under nitrogen in an ice bath, and tributylphosphine (444 mg, 2.2 mM) followed by 1.1 was added. '- (azodicarbonyl) dipiperidine (555 mg, 2.2 mM) was dissolved in tetrahydrofuran (10 ml) The mixture was then stirred for 18 hours, allowing room temperature to rise, then filtered, and the filter cake was washed with tetrahydrofuran. The combined filtrates were evaporated and the residue was purified by chromatography on a 10 g reverse phase C18 column, eluting with a gradient from 10 to 50% acetonitrile in water containing 0.1% tri-acid. Fluoroacetic The relevant fractions were combined, evaporated, and the residue was chromatographed again on a 10 g Mega Bond Elut® silica column, eluting with a gradient increasing in polarity from 0 to 20% methanol in dichloromethane. The relevant fractions were combined and evaporated to give the desired product (104 mg). NMR (DMSO-de) d: 1.49 (s, 9H); 3.92 (m, ÍH); 4.00 (m, 1H); 4.27 (m, 2H); 4.50 (s, 2H); 5.05 (m, ÍH); 6.85 (d, ÍH); 7.53 (t, ÍH); 7.66 (d, ÍH); 7.76 (overlapping m, 2H); 8.67 (d, ÍH); 8.80 (d, 1H). (H of absent OH - exchanged). Example 9 (S) -Isoxazol-3-ylaminomethyl-3- (4- (2-methylimidazol-1-yl) -3-fluorophenyl) oxazolidin-2-one Using essentially the technique of Example 8, but starting from 3- (4- (2-methylimidazol-1-yl) -3-fluorophenyl) -5 (R) -. { N- (t-Butoxycarbonyl) isoxazol-3-ylamino ethyl) oxazolidin-2-one (510 mg, 1.12 mM), and finally isolated by extraction in dichloromethane to give the title product (358 mg). NMR (DMSO-d6) d: 2.16 (s, 3H); 3.46 (t, 2H); 3.87 (dd, 1H); 4.22 (t, ÍH); 4.93 (m, ÍH); 6.01 (d, ÍH); 6.53 (t, ÍH); 6.93 (d, 1H); 7.21 (ÍH); 7.46 (dd, ÍH); 7.55 (t, ÍH); 7. 75 (d, ÍH); 8.39 (d, ÍH). MS (ESP): 358 (MH +) for C17H? 6FN503 Intermediates for this compound were prepared as follows: 3-Fluoro-4- (2-methylimidazol-1-yl) nitrobenzene 2-Methylimidazole (9.02 g, 0.11 'M) was dissolved and -V / N-diisopropy latylamine (32.2 g, 0.25 M) in acetonitrile (160 ml), and added 3, -difluoronitrobenzene (15.9 g, 0.1 M) The mixture was stirred and heated to reflux under nitrogen for 24 hours. The solvent was evaporated, the residue was dissolved in ethyl acetate (300 ml), washed with water (150 ml), brine (150 ml) and dried (magnesium sulfate). The residue was recrystallized from a mixture of ethyl acetate (25 ml) and cyclohexane (150 ml) with the addition of carbon to give the title compound (11.5 g), m.p. 106-107 °. NMR (DMSO-de) d: 2.25 (s, 3H); 7.00 (d, ÍH); 7.35 (t, ÍH); 7.87 (t, ÍH); 8.23 (dd, ÍH); 8.43 (dd, ÍH). MS (ESP): 222 (MH +) for C? 0H8FN302 5-Amino-2- (2-methylimidazol-1-yl) fluorobenzene 3-Fluoro-4- (2-methylimidazol-1-yl) nitrobenzene (40 g , 0.181 M) in a mixture of methanol (200 ml) and tetrahydrofuran (800 ml), cooled to 0 ° under nitrogen, and treated with ammonium formate (57 g, 0.905 M) followed by palladium on carbon (10%). , 2 g) . The mixture was stirred at room temperature for 18 hours, filtered through celite, the celite was washed with methanol (100 ml), and the filtrate was evaporated to dryness. The residue was partitioned between ethyl acetate (800 ml) and 10% aqueous sodium bicarbonate (250 ml). The organic layer was separated, washed with brine (250 ml), dried (magnesium sulfate) and evaporated to give the title compound (34.6 g). NMR (DMSO-d6) d: 2.08 (s, 3H); 5.68 (s, 2H); 6.45 (overlapping m, 2H); 6.84 (d, ÍH); 7.03 (overlapping m, 2H). MS (ESP): 192 (MH +) for C? 0H? 0FN3 5-Benzyloxycarbonylamino-2 (2-methylimidazol-1-yl) fluorobenzene 5-Amino-2- (2-methylimidazol-1-yl) fluorobenzene (34.25 g, 0.179 M) in dry dichloromethane (600 ml) under nitrogen, and cooled to -5 °. Pyridine (17.7 g, 0.224 M) was added, followed by benzyl chloroformate (33.7 g, 0.197 M) for 20 minutes. The mixture was stirred and allowed to rise at room temperature for 16 hours. Aqueous sodium bicarbonate (5%, 250 ml) was added, the organic layer was separated, the aqueous layer was back extracted with dichloxomethane (2 x 300 ml), and the combined extracts were dried (magnesium sulfate). After filtration and evaporation, the residue was recrystallized from toluene (400 ml) to give the title product (54.5 g). NMR (DMSO-de) d: 2.13 (s, 3H); 5.18 (s, 2H); 6.89 (s, ÍH); 7.17 (s, ÍH); 7.41 (overlapping m, 7H); 7.73 (dd, ÍH); 10.21 (br, ÍH). MS (ESP): 326 (MH +) for C? 8H16FN302 3- (3-Fluoro-4- (2-methylimidazol-1-yl) phenyl) -5 (R) -hydroxymethyloxazolidin-2-one 5-Benzyloxycarbonylamino- was dissolved 2- (2-Methylimidazol-1-yl) fluorobenzene (54 g, 0.166 M) in a mixture of dry tetrahydrofuran (600 ml) and 1,3-dimethyl-2, 4, 5, β-tetrahydro-2 (ÍH) pyrimidinone (100 ml) under nitrogen, cooled to -10 °, and treated with a solution of n-butyllithium (1.6M in isohexane, 114 ml) for 30 minutes. After stirring for 30 minutes at -70 °, a solution of. { R) -glycidylbutyrate (26.35 g, 0.183 M) in dry tetrahydrofuran (50 ml) was added for 15 minutes. Stirring was continued for 16 hours and allowed to rise to room temperature. The mixture was treated with aqueous sodium bicarbonate (5%, 500 ml) and ethyl acetate (800 ml), the organic layer was separated, and the aqueous was extracted into additional ethyl acetate (3 x 750 ml). The combined extracts were dried (magnesium sulfate) and evaporated, and the resulting oil was triturated with diethyl ether. The resulting solid was recrystallized from isopropanol to give the title compound (21.5 g).

NMR (DMSO-de) d: 2.16 (s, 3H); 3.56 (dt, ÍH); 3.69 (dt, ÍH); 3.88 (dd, ÍH); 4.15 (t, ÍH); 4.74 (, ÍH); 5.24 (t, ÍH); 6.92 (s, ÍH); 7.20 (s, 1H); 7.48 (dd, ÍH); 7.53 (t, ÍH); 7.74 (dd, ÍH). MS (ESP): 292 (MH +) for C? 4H? 4FN303 3- (4- (2-methylimidazol-1-yl) -3-fluorophenyl) -5 (R) -. { N- (t-butoxycarbonyl) isoxazol-3-yl-aminomethyl) oxazolidin-2-one 3- (2-Methylimidazol-l-yl-3-fluorophenyl) -5 (R) -hydroxymethyloxazolidin-2-one was dissolved (582 mg, 2 mM), 3- (t-butoxycarbonylamino) isoxazole (552 mg, 3 mM) and triphenylphosphine (786 mg, 3 mM) by dry stirring of N, N-dimethylformamide (10 ml) under nitrogen in a bath with ice. Diisopropylazodicarboxylate (606 mg, 3 mM) was added dropwise and the mixture was stirred for 2 hours, allowing the temperature to rise to room temperature. The mixture was diluted with ethyl acetate (100 ml), washed with water (100 ml), 2% aqueous sodium bicarbonate (100 ml), and brine (100 ml). After drying (magnesium sulfate), the residue was purified by chromatography on a 20 g Mega Bond Elut® silica column, eluting with a gradient increasing in polarity from 0 to 5% methanol in dichloromethanol. The relevant fractions were combined to give the desired product (590 mg). NMR (DMSO-de) d: 1.47 (s, 9H); 2.14 (s, 3H); 3.91 (dd, ÍH); 4.00 (dd, ÍH); .4.25 (dd, ÍH); 4.29 (t, ÍH); 5.02 (m, ÍH); 6.85 (d, ÍH); 6.92 (d, 1H); 7.20 (d, "lH); 7.47 (dd, ÍH); 7.55 (t, ÍH); 7.71 (dd, ÍH); 8.79 (d, ÍH) MS (ESP): 458 (MH +) for C22H24FN5? 5 Example 10: 5 (S) -Isoxazol-3-ylaminomethyl-3- (4- (4-methylimidazol-1-yl) -3-luo-phenyl) -oxazolidin-2-one Using essentially the technique of Example 9, but starting from. of 3- (4- (4-methylimidazol-1-yl) -3-fluorophenyl) -5- (R) - (N- (t-butoxycarbonyl) isoxzol-3-ylaminomethyl) oxazolidin-2-one (190 mg, 0/41 mM), and purifying the material from the dichloromethane extraction by chromatography on a 20 g Mega Bond Elut® silica column, eluting with a gradient increasing in polarity from 0 to 10% methanol in dichloromethane The relevant fractions were combined to give the title compound (128 mg): - - MR (DMS0-d6) d: 2.15 (s, 3H), 3.45 (t, 2H), 3.86 (dd, ÍH); 4.21 (t, ÍH); 4.91 (m, ÍH); 5.99 (d, ÍH); 6.56 (t, ÍH); 7.21 (d, ÍH); 7.43 (dd, ÍH); 7.63 (t, ÍH); 7.74 (dd, ÍH); 7.86 (d, ÍH). MS (ESP): 358 (MH +) for C? 7H? 6F? 503 Intermediates for this compound were prepared as follows: 3-Fluo "ro-4- (4-methylimidazol-1-yl) nitrobenzene 4-methylimidazole was dissolved (45.1 g, 0.55 M) and α, β-diisiopropylethylamine (161 g, 1.25 M) in acetonitrile (800 ml), and 3,4-difluoronitrobenzene (79.5 g 0.5 M) was added.The mixture was stirred and heated to reflux under nitrogen for 24 hours The solvent was evaporated, the residue was dissolved in ethyl acetate (800 ml), washed with water (400 ml), brine (200 ml), and dried (magnesium sulfate). it was dissolved in toluene (250 ml), treated with charcoal, filtered and diluted with hot cyclohexane (75 ml) to "crystallize 3-fluoro-4- (4-methylimidazol-1-yl) nitrobenzene (64.7 g). NMR (DMSO-ds) d: 2.18 (s, 3H); 7.29 (s, 1H); 7.92 (t, ÍH); 8.07 (s, ÍH); 8.18 (dd, ÍH); 8.38 (dd, ÍH). MS (ESP): 222 (MH +) for C? 0H8FN3O2 5-Amino-2- (4-methylimidazol-1-yl) fluorobenzene 3-Fluoro-4- (4-methylimidazol-1-yl) nitrobenzene (64.7 g, 0.293 M) in a mixture of methanol (200 ml) and tetrahydrofuran (800 ml), cooled to 0 ° under nitrogen, and treated with ammonium formate (99.3 g, 1.46 M) followed by palladium on carbon (10%). , 2.5 g). The mixture was stirred at room temperature for 48 hours, filtered through celite, the celite was washed with methanol (200 ml), and the filtrate was evaporated to dryness. The residue was partitioned between ethyl acetate (800 ml), and 10% aqueous sodium bicarbonate (250 ml). The organic layer was separated, washed with brine (250 ml), dried (magnesium sulfate) and evaporated to give the title compound (50.6 g). NMR (DMSO-de) d: 2.12 (s, 3H); 5.60 (br s, 2H); 6.42 (dd, ÍH); 6.47 (dd, ÍH); 6.98 (s, ÍH); 7.11 (t, ÍH); 7.60 (s, ÍH).

MS (ES P): 1 92 (MH +) for C? 0H? 0FN3 5-Benzyloxycarbonylamino-2- (4-methylimidazol-1-yl) fluorobenzene 5-Amino-2- (4-methylimidazol-1-yl) was dissolved fluorobenzene (50.6 g, 0.265 M) in dry dichloromethane (800 ml) under nitrogen, and cooled to -5o. Pyridine was added (26.1 g, 0.33 M), followed by benzyl chloroformate (49.9 g, 0.292 M) for 30 minutes. The mixture was stirred and the temperature was allowed to rise to ambient for 16 hours. Aqueous sodium bicarbonate (5%, 350 ml) was added, the organic layer was separated, and the aqueous layer was back extracted with dichloromethane (2 x 200 ml), and the combined organics were dried (magnesium sulfate). After filtration and evaporation, the residue was recrystallized from toluene (300 ml) to give the title product (80 g). NMR (DMSO-de) d: 2.15 (s, 3H); 5.16 (s, 2H); 7.13 (s, ÍH); 7.31 (dd, ÍH); 7.41 (m, 5H); 7.48 (t, ÍH); 7.57 (dd, 1H); 7.78 (s, ÍH); 10.15 (br s, ÍH); MS (ESP): 326 (MH +) for ClsH? GFN302 3- (3-Fluoro-4- (4-methylimidazol-1-yl) phenyl) -5 (R) -hydroxymethyloxazolidin-2-one 5-Benzyloxycarbonylamino- was dissolved 2- (4-Methylimidazol-1-yl) fluorobenzene (54 g, 0.166 M) in a mixture of dry tetrahydrofuran (600 ml) and 1,3-dimethyl-2,4,5,6-tetrahydro2 (1H) -pyrimidinone (100 ml) under nitrogen, cooled to -10 °, and treated with a solution of n-butyllithium (1.6 M in isohexane, 114 ml), for 30 minutes After stirring for 30 minutes at -10 °, a solution of. { R) -glycidylbutyrate (26.35 g, 0.183 M) in dry tetrahydrofuran (50 ml) was added for 15 minutes. The stirring was continued for 16 hours allowing the temperature to rise to ambient. The mixture was treated with aqueous sodium bicarbonate (5%, 500 ml) and ethyl acetate (800 ml), and the undissolved solid was stirred and washed well with diethyl ether to give the title product (16.3 g). The aqueous layer was further extracted with ethyl acetate (2 x 750 ml), the combined extracts were dried (magnesium sulfate), and evaporated, and the residue was triturated with diethyl ether. The resulting solid was recrystallized from ethanol to give more product (10.9 g). NMR (DMSO-de) d: 2.13 (s, 3H); 3.56 (dd, ÍH); 3.68 (dd, 1H); 3.86 (dd, ÍH); 4.11 (t, ÍH); 4.73 (m, ÍH); 5.21 (br, ÍH); 7.18 (s, ÍH); 7.45 (dd, 1H); 7.60 (t, ÍH); 7.73 (dd, ÍH); 7.83 (s, ÍH). MS (ESP): 292 (MH +) for C? 4H? 4FN303 3- (3-fluoro-4- (4-methylimidazol-1-yl) phenyl) -5 (R) -methanesulfonyloxymethyloxazolidin-2-one Was stirred 3- (3-fluoro-4- (4-methylimidazol-1-yl) phenyl) -5 (R) -hydroxymethyloxazolidin-2-one (11.8 g, 40.5 mM) in a mixture of pyridine (200 ml) and triethylamine (4.86 g) , 48.2 mM) under nitrogen in a bath with ice. Methanesulfonyl chloride (5.16 g, 45 mM) was added dropwise, and the mixture was stirred for 2 hours, allowing the temperature to rise to room temperature. The solvent was evaporated, and the residue was stirred vigorously with a mixture of aqueous sodium bicarbonate (5%, 200 ml), and isohexane (200 ml). The precipitate was filtered, washed with water, then isohexane (300 ml) to give the title product (11.7 g), m.p. 151-53 °. NMR (DMSO-de) d: 2.16 (s, 3H); 3.27 (s, 3H); 3.88 (dd, 1H); 4.24 (t, ÍH); 4.47 (dd, ÍH); 4.54 (dd, ÍH); 5.04 (m, ÍH); 7.20 (d, ÍH); 7.45 (dd, ÍH); 7.63 (t, 1H); 7.73 (dd, 1H); 7.85 (t, 1H). MS (ESP): 292 (MH +) for C? 5H? 6FN305S 3- (4- (4-Methylimidazol-1-yl) -3-fluorophenyl) -5 (R) - (N- (t -butoxycarbonyl) isoxazole- 3-yl-aminomethyl) oxazolidin-2-one Sodium hydride (50% in oil, 72 mg, 1.5 mM) was stirred in N,? J-dimethylformamide (3 ml) under nitrogen, and dissolved 3- (t- butoxycarbonylamino) isoxazole (276 mg, 1.5 mM) in -V, jV-diemylformamide (4 ml) added. After stirring for 10 minutes, 3- (4-methylimidazol-1-yl-3-fluorophenyl) -5 (R) -methanesulfonyloxymethyloxazolidin-2-one (369 mg, 1 mM) was added, the mixture was heated to 35 °. for 1.5 hours. The mixture was diluted with aqueous sodium bicarbonate (30 ml), taken up in ethyl acetate (3 x 20 ml), and the extract was washed with water (2 x 20 ml), and brine (20 ml). After drying (magnesium sulfate), the residue was purified by chromatography on a 20 g Mega Bond Elut® silica column, eluting with a gradient increasing in polarity from 0 to 50% acetone in dichloromethane. The relevant fractions were combined to give the desired product (228 mg). NMR (DMSO-d6) d: 1.49 (s, 9H); 2.17 (s, 3H); 3.90 (dd, ÍH); 4.01 (m, ÍH); 4.25 (t, ÍH); 4.28 (dd, ÍH); 5.04 (m, ÍH); 6.86 (d, ÍH); 7.22 (d, ÍH); 7.46 (dd, ÍH); 7.63 (t, ÍH); 7. 72 (dd, ÍH); 7.86 (d, ÍH); 8.81 (d, 1H). MS (ESP): 458 (MH +) for C22H2 FN505 Example 11: 5 () -Isoxazol-3-ylaminomethyl-3- (4- (3- (S) - (fc-butoxycarbonyl) aminopyrrolidin-1-yl) -3-fluorophenyl) oxazolidin-2 -one The title compound was prepared using essentially the method of Example 7, starting from 3- (4- (3- (S) - (t-butoxycarbonyl) aminopyrrolidin-1-yl) -3-fluorophenyl) -5 (R) - (N- (2,2, 2-trichloroethyloxycarbonyl) -ioxazol-3-ylaminomethyl) oxazolidin-2-one (320 mg, 0.5 mM). The residue after filtration and evaporation was partitioned between water (10 ml) and ethyl acetate (10 ml), and the organic phase was washed with water (2 x 10 ml), aqueous sodium bicarbonate (10 ml), dried (magnesium sulfate), and evaporated. Recrystallization from isopropanol (40 ml) gave the desired product (173 mg). MR (DMSO-de) d :. 1.37 (s, 9H); 1.80 (hextet, ÍH); 2.07 (hextet, ÍH); 3.10 (m, ÍH); 3.24 (m overlapped by H20, ~ 1H); 3.42 (overlapping m, 3H); 3.48 (m, ÍH); 3.74 (dd, 1H); 4.06 '(overlapping m, 2H); 4.81 (m, ÍH); 5.98 (d, ÍH); 6.50 (t, ÍH); 6.71 (t, 1H); 7.07 (dd, ÍH); 7.12 (br, 1H); 7.37 (dd, ÍH); 8.37 (d, ÍH). MS (ESP): 462 (MH +) for C22H28FN505 Intermediates for this compound were prepared as follows: 3-Fluoro-4- (3 (S) - (-butoxycarbonyl) aminopyrrolidin-1-yl) nitrobenzene 3, 4- was dissolved Difluoronitrobenzene (17.1 g, 0.108 M) in acetonitrile (300 ml), and treated with N, N-diisopropylethylamine (34.8 g, 0.27 M) and 3 (S) - (t-butoxycarbonyl) -aminopyrrolidine (20 g, 0.108 M). The mixture was stirred and heated to reflux for 18 hours. The solvent was evaporated, and the residue was dissolved in ethyl acetate (600 ml). The organic layer was washed with water (150 ml), aqueous sodium diacid phosphate (5% in water, 150 ml), aqueous sodium bicarbonate ( 100 ml) brine (100 ml) and dried (magnesium sulfate). Evaporation gave the desired product as a yellow solid (33.5 g), of sufficient quality for use without purification. NMR (DMSO-de) d: 1.36 (s, 9H); 1.87 (m, ÍH); 2.08 (m, ÍH); 3.36 (m, ÍH); 3.54 (, ÍH); 3.62 (tm, ÍH); 3.73 (m, ÍH); 4.09 (m, ÍH); 6.72"(t, ÍH); .7.19 (d, ÍH); 7.88 (overlapping m, 2H) MS (ESP): 326 (MH +) for CisH ^ F ^ 5-Amino-2- (3 (S) - (t-butoxycarbonyl) aminopyrrolidin-1-yl) fluorobenzene 3-Fluoro-4- (3- (S) - (t-butoxycarbonyl) aminopyrrolidin-1-yl) nitrobenzene (33.5 g, 0.103 M) was dissolved in ethyl acetate (500 1) was treated with palladium catalyst (10% on carbon, 5 g) and hydrogenated at atmospheric pressure until the theoretical incorporation of the gas After filtering through celite and evaporation, the required product was obtained as a red gum of sufficient quality for use without purification (30.4 g), NMR (DMSO-de) d: 1_.35 (s, 9H), 1.71 (m, ÍH), 2.06 (m, ÍH), 2.87 (dd, ÍH) ), 3.05 (m, 1H), 3.11 (m, ÍH), 3.26 (m overlapping H20, ~ 1H), 3.97 (m, ÍH), 4.68 (s, 2H), 6.25 (dd, ÍH), 6.31 (dd) , HH), 6.51 (t, HH), 7.03 (d, HH), MS (ESP): 296 (MH +) for C 5 5H22FN302 5-Ethoxycarbonylamino-2 (3- (S) - (t-butoxycarbonyl) aminopyrrolidin- 1-yl) fluorobenzene 5-Amino-2- (3 (S) - (-butoxycarbonyl) aminopyrrolidin-1-yl) fluorobenzene (30.4 g, 0.1 Q3 M) was dissolved in dry pyridine (150 ml) and cooled under nitrogen with stirring at 0 °. Ethyl chloroformate (12.3, 0.113 M) was added dropwise, and the mixture was stirred for 1 hour at the same temperature. Ice-water (250 ml) was added, and stirring was continued for 1 hour. The resulting precipitate was collected, washed thoroughly with water, and dried with air. The residue was treated with toluene, turned azeotrope at medium volume, then treated with isohexane 8500 ml), to precipitate the desired product. (35.3 g). NMR (DMSO-d6) d: 1.21 (t, 3H); 1.37 (s, 9H); 1.77 (m, ÍH); 2.06 (m, ÍH); 3.04 (m, ÍH); 3.20 (dd, 1H); 3.30 (m overlapping H20, ÍH); 3.42 (tm, ÍH); 4.02 (br, ÍH); 4.08 (q, 2H); 6.63 (t, 1H); 7.02 (d, ÍH); 7.08 (br, ÍH); 7.22 (d, ÍH); 9.38 (s, ÍH). MS (ESP): 368 (MH +) for C? 8H26FN304 3- (3-Fluoro-4- (3- (S) - (t-butoxycarbonyl) aminopyrrolidin-1-yl) 5 (R) -hydroxymethyloxazolidin-2-one 5-Ethoxycarbonylamino-2 (3 (S) - (t-butoxycarbonyl) aminopyrrolidin-1-yl) fluorobenzene (35.2 g, 0.096M) was dissolved in dry tetrahydrofuran (400 ml) under nitrogen, cooled to -10 °, and was treated by dripping for 20 minutes with a solution of lithium t-butoxide, was prepared from t-butanol (9.3 g, 123 mM) in dry tetrahydrofuran (70 ml) and n-butyllithium (66 ml, 1.6 M in hexane.) After stirring for 20 minutes, (J?) -glycidylbutyrate (15.2 g, 0.102 M) in tetrahydrofuran (20 ml) was added over 10 minutes, and the temperature was allowed to rise to room for 16 hours. The mixture was treated with methanol (10 ml), stirred at room temperature for 10 minutes, then treated with a mixture of 5% aqueous sodium bicarbonate (250 ml) and ethyl acetate. (500 ml). The precipitate was collected and washed well with ethyl acetate to give the desired product (19.5 g). The filtrate was separated in an organic layer, which was dried (magnesium sulfate) and evaporated. The residue was refluxed briefly with ethyl acetate (100 ml), cooled, and filtered to give the additional product (16.6 g). NMR (DMS0-d6) d: 1.37 (s, 9H); 1.79 (m, ÍH); 2.07 (my h); 3.08 (m, ÍH); 3.24 (m, overlapping H20, ~ 1H); 3.36 (m, 1H); 3.48 (tm, ÍH); 3.53 (d, ÍH); 3.63 (d, 1H); 3.74 (dd, 1 HOUR); 3.99 (t, ÍH); 4.04 (m, ÍH); 4.63 (m, 1H); 5.15 (s, ÍH); 6. 71 (t, ÍH); 7.08 (dd overlapping by, 2H); 7.39 (dd, 1H). MS (ESP): 396 (MH +) for C? 9H26FN305 3- (4- (3- (-Butoxycarbonyl) aminopyrrolidin-1-yl) -3-fluorophenyl) -5 (R) - (N- (2.2, 2-trichloroethyloxycarbonyl) isoxazol-3-ylaminomethyl) oxazolidin-2-one The title compound was prepared using essentially the method of Example 7, starting from 3- (3-fluoro-4- (3 (S) - (t -butoxycarbonyl) aminopyrrolidin-1-yl) -5 (R) -hydroxymethyloxazolidin-2-one (2.0 g, 5.06 mM) The unpurified material was purified by chromatography on a 90 g Botage silica column, eluting with a gradient Increasing in polarity from 0 to 5% ethyl acetate in dichloromethane The relevant fractions were combined and evaporated to give the desired product (2.92 g): MR (DMSO-de) d: 1.38 (s, 9H); 1.81 (hextet, ÍH); 2. 08 (hextet, ÍH); 3.11. (M, ÍH); 3.25 (m overlapping H20, ~ 1H); 3.37 '(m, ÍH); 3.48 (tm, ÍH); 3.82 (dd, ÍH); 4.03 (m, 1H); 4.13 (overlapping m, 2H); 4.35 (dd, ÍH); 4.98 (d overlapping m, 2H); 5.08 (d, ÍH); 6.71 (t, ÍH); 6.88 (d, ÍH); 7.08 (dd overlapping br, 2H); 7.34 (dd, ÍH); 8.89 (d, ÍH). MS (ESP): 636 (MH +) for C 25 H 29 Cl 13 FN 50 Example 12 5 (S) -isoxazol-3-ylaminomethyl-3- (4- (3 () -acetamidopyrrolidin-1-yl) -3-luo-phenyl) -oxazolidin-2-one The title compound was prepared using essentially the method of Example 11, starting from 3- (4- (3 (S) -acetamidopyrrolidin-1-yl) -3-fluorophenyl) -5 (R) - (N- ( 2,2,2-trichloroethyloxycarbonyl) isoxazol-3-ylaminomethyl) oxazolidin-2-one (250 mg, 0.432 M). The residue after the extractive treaty was purified by chromatography on a 10 g Mega Bond Elut® silica column, eluting with a gradient increasing in polarity from 0 to 10% methanol in dichloromethane. The relevant fractions were combined and evaporated to give the desired product 8104 mg). MR (DMSO-de) d: 1.78 (s overlapping m, 4H); 2.11 (hextet, 1H); 3.09 (m, 1H); 3.24 (m, overlapped by H20, ~ 1H); 3.40 (t overlapping, 3H); 3.47 (m, ÍH); 3.72 (dd, ÍH); 4.06 (t, ÍH); 4.26 (hextet, ÍH); 4.81 (m, ÍH); 5.97 (d, 1H); 6.49 (t, ÍH); 6.72 (t, 1H); 7.08 (dd, ÍH); 7.39 (dd, ÍH); 8.08 (d, ÍH); 8.37 (d, ÍH). MS (ESP): 404 (MH +) for C? 9H22F 5? 4 Intermediates for this compound were prepared as follows: 3- (4- (3 (S) -Aminopyrrolidin-1-yl) -3-fluorophenyl) -5 (R) - (N- 2.2 , 2-trichloroethyloxycarbonyl) isoxazol-3-ylaminomethyl) oxazolidin-2-one. 3- (4- (2 (S) - (t-Butoxycarbonyl) aminopyrrolidin-1-yl) -3-fluorophenyl) -5 (R) was dissolved. - (N- (2,2-, 2-trichloroethyloxycarbonyl (isoxazol-3-ylaminomethyl) oxazolidin-2-one (1.03 g, 1.62 mM) in dichloromethane (5 ml) under nitrogen and treated with a solution of acid chloride in ethanol (3.8 M, 25 ml) After stirring 5 hours at room temperature, the solvent was removed, and the residue was repeatedly evaporated with portions of dichloromethane to give the hydrochloride salt of the desired product as a white foam (962 mg). MR (DMSO-de) d: 2.02 (hextet, ÍH); 2.25 (hextet, ÍH); 3.26 (dd, ÍH); 3.42 (, overlapped by solvent, ~ 1H); 3. 53 (m, 2H); 3.84 (dd overlapping m, 2H); 4.15 (m, 2H); 4.35 (dd, 1H); 4.97 (d, 1H); 5.02 (m, ÍH); 5.08 (d, ÍH); 6.77 (t, ÍH); 6.88 (d, ÍH); 7.12 (dd, ÍH); 7.39 (dd, ÍH); 8.48 (br, 3H); 8.91 (d, ÍH). (proton +1 for HCl salt). MS (ESP): 536 (MH +) for C2oH2? Cl3F? 505 3- (4- (3 (S) -Acetamidopyrrolidin-1-yl) -3-fluorophenyl) -5 (R) - (N- (2, 2, 2-trichloro-ethyloxycarbonyl) isoxazol-3-ylaminomethyl) oxazolidin-2-yone. 3- (4- (3 () - Aminopyrrolidin-1-yl) -3-fluorophenyl) -5 hydrochloride salt was dissolved. R) - (N- (2,2,2-trichloroethyloxycarbonyl) isoxazol-3-ylaminomethyl) oxazolidin-2-one (400 mg, 0.74 mM) in water (5 ml) and treated with aqueous sodium bicarbonate solution ( 5 ml) and dichloromethane (10 ml) in an ice bath. Acetic anhydride 8216 mg, 2 mM) was added, the mixture was stirred 18 hours, allowing to raise the temperature to room, followed by the addition of an additional portion of acetic anhydride (216 mg), and an additional period of 10 hours of stirring . The organic phase was separated, washed with aqueous sodium hydrogen phosphate (2%, 2 x 15 ml), brine (10 ml), and dried (magnesium sulfate). Evaporation gave the desired product (338 mg). MR (DMSO-d6) d: 1.79 (s overlapping m, 4H); 2.11 (hextet, ÍH); 3.11 (m, ÍH); 3.26 (m overlapped by H20, ~ 1H); 3.40 (dd, ÍH); 3.49 (m, ÍH); 3.82 (dd, ÍH); 4.13 (t overlapping dd, 2H); 4.27 (dd, ÍH); 4.35 (dd, ÍH); 4.97 (d, ÍH); 5.01 (m, 1H); 5.07 (d, ÍH); 6.73 (t, ÍH); 6.88 (d, ÍH); 7.08 (dd, ÍH); 7.35 (dd, ÍH); 8.08 (d, ÍH); 8.89 (d, ÍH). MS (ESP): 578 (MH +) for C22H23C13F? 506 Example 13: 5 (S) -Isoxazol-3-ylaminomethyl-3- (4- (3 (S) -metanesulfonamido-pyrrolidin-1-yl) -3-fluorophenyl Oxazolidin-2-one The title compound was prepared using essentially the method of Example 11, starting from 3- (4- (3- (S) -metanesulfonamidopyrrolidin-1-yl) -3-fluorophenyl) -5 ( R) - (N- (2,2, 2-trichloroethyloxycarbonyl) isoxazol-3-ylaminomethyl) oxazolidin-2-one (250 mg, 0.407 mM). The residue after the extractive treaty was purified by chromatography on a 10 g Mega Bond Elut® silica column, eluting with a gradient increasing in polarity from 0 to 7% methanol in dichloromethane. The relevant fractions were combined and evaporated to give the desired product (94 mg). MR (DMSO-de) d: 1.86 (hextet, ÍH); 2.19 (hextet, ÍH); 2.94 (s, 3H); 3.20 (m, ÍH); 3.27 (m overlapped by H20, ~ 1H); 3.34 (m, ÍH); 3.40 (t, 2H); 3.54 (t, ÍH); 3.72 (dd, ÍH); 3.97 (m, ÍH); 4.06 (t, ÍH); 4.81 (m, ÍH); 5.98 (d, ÍH); 6.48 (t, 1H); 6.72 (t, ÍH); 7.08 (dd, ÍH); 7.35 (s, ÍH); 7.37 (dd, ÍH); 8.36 (d, 1H). MS (ESP): 440 (MH +) for C? 8H22F? 505S The 3- (4- (3- (S) -Metanesulfonamidopyrrolidin-1-yl) -3-flurofenl) -5 (R) - (N- (2 , 2, 2-trichloroethyloxycarbonyl) isoxazol-3-ylaminomethyl) oxazolidin-2-one intermediate was prepared as follows: Using essentially the method for the intermediate of Example 12, starting from the hydrochloride salt of 3- (4- (3 (S) -aminopyrrolidin-1-yl) -3-fluorophenyl) -5 (R) - (N- (2,2,2, -trichloroethyloxycarbonyl) isoxazol-3-ylaminomethyl) oxazolidin-2-one (400 mg, 0.74 mM) and methanesulfonyl chloride gave the desired product (361 mg) ..? MR (DMSO-de) d: 1.87 (hextet, ÍH); 2.19 (hextet, ÍH); 2.97 (s, 3H); 3.20 (m, ÍH); 3.30 (, ÍH); 3.37 (m, ÍH); 3.54 (m overlapped by H20, ~ 1H); 3.83 (dd, ÍH); 3.97 (dd, 1H); 4.13 (dd overlapping m, 2H); 4.36 (dd, ÍH); 4.97 (d, ÍH); 5.02 (m, ÍH); 5.07 (d, ÍH); 6.74 (t, ÍH); 6.88 (d, ÍH); 7.09 (dd, ÍH); 7.36 (dd overlapping br, 2H); 8.89 (d, ÍH). MS (ESP): 578 (MH +) for C2? H23Cl3FN507S Example 14: 3- (4- (3 (S) -Mtoxycarbonylaminopyrrolidin-1-yl) -3-fluoro enyl) -5 (S) - (isoxazole-3) ilaminomethyl) oxazolidin-2-one The title compound was prepared using essentially the method of Example 11, starting from 3- (4- (3- (S) -methoxycarbonylaminopyrrolidin-1-yl) -3-fluorophenyl) -5 (R) - (N- (2,2,2-trichloroethyloxycarbonyl (isoxazol-3-ylaminomethyl) oxazolidin-2-one (250 mg, 0.407 mM) The residue after the extractive workup was purified by chromatography on a 10 g Mega Bond Elut® silica, eluting with a gradient increasing in polarity from 0 to 100% ethyl acetate in dichloromethane The relevant fractions were combined and evaporated to give the desired product 891 mg).? MR (DMS0 -d6) d: 1.82 (hextet, ÍH); 2.10 (hextet, ÍH); 3.13 (m, 1H); 3.26 (m overlapped by H20, ~ 1H); 3.39 (m, 3H); 3.48 (t, ÍH); 3.52 (s, 3H); 3.73 (dd, ÍH); 4.07 (t, ÍH); 4.10 (m, ÍH); 4.82 (m, ÍH); 5.98 (d, ÍH); 6.48 (t, ÍH); 6.71 (t, ÍH); 7.08 (dd, ÍH); 7.37 (dd, ÍH); 7.42 (s, ÍH); 8.35 (d, ÍH).

MS (ESP): 420 (MH +) for C? 9H22FN505 3- (4- (3- (S) -methoxycarbonylaminopyrrolidin-1-yl) -3-fluorophenyl) -5 (R) - (N- (2.2 , 2-trichloroethyloxycarbonyl) isoxazol-3-ylaminomethyl) oxazolidin-2-one was prepared as follows: Using essentially the method for the intermediate of Example 12, starting from the hydrochloride salt of 3- (4- (3- ( S) -aminopyrrolidin-1-yl) -3-fluorophenyl) -5 (R) - (N- (2, 2, 2-trichloroethyloxycarbonyl) isoxazol-3-ylaminomethyl) oxazolidin-2-one (360 mg, 0.63 mM ) and methyl chloroformate gave the desired product (280 mg). MR (DMSO-de) d: 1.84 (hextet, ÍH); 2.13 (hextet, ÍH); 3.15 (m, ÍH); 3.35 (m overlapped by H20, ~ 2H); 3.55 (s overlapping m, 4H); 3.84 (dd, ÍH); 4.13 (overlapping m, 3H); 4.36 (dd, ÍH); 4.98 (d, ÍH); 5.04 (m, ÍH); 5.08 (d, ÍH); 6.73 (t, ÍH); 6.89 (d, ÍH); 7.08 (dd, ÍH); 7.35 (dd, ÍH); 7.43 (br, 1H); 8.93 (d, ÍH). MS (ESP): 594 (MH +) for C22H23C13F? 507 Example 15: 3- (4- (3- (S) -Acetoxyacetamidopyrrolidin-1-yl) -3-fluorophenyl) -5 (S) - (isoxazole-3) ilaminomethyl) oxazolidin-2-one The title compound was prepared using essentially the method of Example 11, starting from 3- (4- (3 (S) -acetoxyacetamidopyrrolidin-1-yl) -3-fluorophenyl) -5 ( R) - (N- (2, 2, 2-trichloroethyloxycarbonyl) isoxazol-3-ylaminomethyl) oxazolidin-2-one (390 mg, 0.62 mM). The residue after the extractive treaty was purified by chromatography on a 10 g Mega Bond Elut® silica column eluting with a gradient increasing in polarity from 0 to 100% ethyl acetate in dichloromethane. The relevant fractions were combined and evaporated to give the desired product (100 mg). NMR (DMSO-d6) d: 1.83 (hextet, ÍH); 2.06 (s, 3H); 2.14 (hextet, ÍH); 3.13 (m, ÍH); 3.24 (m overlapped by H20, ~ 2H); 3.40 (t, 2H); 3.49 (m, ÍH); 3.73 (dd, ÍH); 4.06 (t, ÍH); 4.32 (m, ÍH); 4.42 (s, 2H); 4.81 (m, ÍH); 5.97 (d, ÍH); 6.49 (t, 1H); 6.73 (t, ÍH); 7.08 (dd, ÍH); 7.39 (dd, 1H); 8.23 (d, ÍH); 8.36 (d, ÍH). MS (ESP): 462 (MH +) for C21H24FN506 3- (4- (3- (S) -Acetoxyacetamidopyrrolidin-1-yl) -3-fluorophenyl) -5 (R) - (N- (2, 2, 2-trichloroethyloxycarbonyl) isoxazol-3-ylaminomethyl) oxazolidin-2-one intermediate, was prepared as follows: The hydrochloride salt of 3- (4- (3- (S) -Aminopyrrolidin-1-yl) -3-fluorophenyl was suspended ) -5 (R) - (N- (2,2,2-trichloroethyl-oxycarbonyl) isoxazol-3-ylaminomethyl) oxazolidin-2-one (400 mg, 0.698 mM) in dichloromethane (10 ml) under nitrogen at 0 ° . Triethylamine (282 mg, 2.79 mM) was added, the solution was treated by dripping with acetoxyacetyl chloride (145 mg, 1.05 mM) and then stirred for 1 hour at room temperature. The mixture was diluted with dichloromethane (10 ml), washed with aqueous sodium dihydrogen phosphate (10%, 10 ml), aqueous sodium bicarbonate (10 ml) and water (10 ml), and dr(magnesium sulfate). . Trituration of the residue after evaporation with diethyl ether / isohexane (1: 1 10 ml) gave the desired product (440 mg). NMR (DMSO-de) d: 1.83 hextet, ÍH); 2.06 (s, 3H); 2. 13 (hextet, ÍH); 3.14 (m, ÍH); 3.27 (m overlapped by H20, ~ 1H); 3.40 (m, ÍH); 3.50 (m, ÍH); 3.82 (dd, ÍH); 4.13 (overlapping m, 2H); 4.33 (overlapping m, 2H); 4.52 (s, 2H); 4.97 (d, ÍH); 5.03 (m, 1H); 5.07 (d, ÍH); 6.74 (t, 1H); 6.88 (d, ÍH); 7.09 (dd, ÍH); 7.35 (dd, ÍH); 8.25 (d, ÍH); 8.89 (d, ÍH). MS (ESP): 636 (MH +) for C 24 H 25 C 13 FN 508 Example 16: 3- (4- (3 (S) -Hidoxyacetamidopyrrolidin-1-yl) -3- l-chlorophenyl) -5 (S) - (isoxazol-3-ylaminomethyl) oxazolidin-2-one. They were stirred at room temperature 3- (4- (3 (S) -Acetoxyacetmaidopyrrolidin-1-yl) -3-fluorophenyl) -5 (S) - (3-isoxazolylaminomethyl) oxazolidin-2-one (105 mg, 0.23 mM) and potassium carbonate (300 mg, 2.2 M) under nitrogen in methanol (20 ml) for 20 minutes. The mixture was evaporated to dryness and triturated with water (10 ml) to give the desired product (77 mg). NMR (DMS0-d6) d: 1.83 (hextet, ÍH); 2.14 (hextet, ÍH); 3.20 (m, ÍH); 3.29 (overlapped by H20, ~ 1H); 3.42 (t overlapping m, 3H); 3.49 (m, ÍH); 3.75 (dd, ÍH); 3.82 (s, 2H); 4.07 (t, ÍH); 4.37 (1H); 4.83 (m, ÍH); 5.37 (br, ÍH); 6.00 (d, ÍH); 6.51 (t, 1H); 6.75 (t, 1H); 7.10 (dd, ÍH); 7.41 (dd, ÍH); 7.85 (d, ÍH); 8.37 (d, ÍH). MS (ESP): 420 (MH +) for C? 9H22FN505 Example 17: 3- (4- (3 (S) - (2 (S), 3-Dihydroxypropanoyl) pyrrolidin-1-yl) -3-fluorophenyl) -5 (S) - (isoxazol-3-ylaminome il) oxazolidin-2-one The title compound was prepared using essentially the method of Example 7, starting from 3- (4- (3- (S) - (2, 2-dimethyl-l, 3-dioxolan-4 (S) -ylcarbonamido) pyrrolidin-1-yl) -3-fluorophenyl) -5 (R) - (N- (2,2,2-trichloroethyloxycarbonyl) isoxazole-3- ilaminomethyl) oxazolidin-2-one (380 mg, 0.572 mM). The residue after filtration and evaporation was dissolved in tetrahydrofuran (6 ml), treated with 2M aqueous hydrochloric acid (4 ml), and stirred at room temperature for 20 hours. Anhydrous potassium carbonate was added in excess, the solution was filtered, evaporated, and the residue was purifby chromatography on a 10 g Mega Bond Elut® silica column, eluting with a gradient increasing in polarity from 0 to 20. % methanol in dichloromethane. The relevant fractions were combined and evaporated to give the desired product (130 mg). MR (DMSO-de) d: 1.91 hextet, ÍH); 2.13 (hextet, ÍH); 3.20-3.50 (overlapping m, ~ 7H); 3.57 (dd ,, lH); 3.74 (dd, ÍH); 3.87 (t, ÍH); 4.08 (t, ÍH); 4.35 (m, ÍH); 4.83 (m, ÍH); 6.00 (d, ÍH); 6.50 (t, ÍH); 6.73 (t, ÍH); 7.11 (dd, ÍH); 7.40 (dd, ÍH); 7.80 (d, ÍH); 8.38 (d, ÍH). (2 x OH exchanged, not seen). MS (ESP): 450 (MH +) for C20H24FN5? 6 The 3- (4- (3 (S) - (2,2-dimethyl-l, 3-dioxolan-4 (S) -ylcarbonamido) pyrrolidin-1-yl ) -3-fluorophenyl) -5 (R) - (N- (2, 2, 2-trichloroethyloxycarbonyl) isoxazol-3-ylaminomethyl) -oxazolidin-2-one intermediate was prepared as follows: The hydrochloride salt was treated by dripping 3- (4- (3 (S) -Aminopyrrolidin-1-yl) -3-fluorophenyl) -5 (R) - (N- (2,2,2-trichloroethyl-oxycarbonyl) isoxazole) -3-ylaminomethyl) oxazolidin -2-one (400 mg, 0.698 mM) in pyridine (5 ml) with a solution of 2,2-dimethyl-1,3-dioxolan-4 (S) -ylcarbonyl chloride (200 mg, 1.2 mM) in dichloromethane (2 ml), and the mixture was stirred 3 hours at room temperature. The mixture was diluted with ethyl acetate (15 ml) and water (15 ml), the organic layer was separated, washed with aqueous sodium bicarbonate (10 ml) and brine (10 ml), and evaporated, then turned azeotrope with toluene (20 ml). The residue was purifby chromatography on a 10 g Mega Bond Elut® silica column, eluting with a gradient increasing in polarity from 0 to 100% ethyl acetate in dichloromethane. The relevant fractions were combined and evaporated to give the desired product (435 mg). MR (DMSO-d6) d: 1.30 (s, 3H); 1.37 (s, 3H); 1.89 (hextet, ÍH); 2.13 (hext.et, ÍH); 3.20 (m, ÍH); 3.24 (m overlapped by H20, ÍH); 3.39 (m, ÍH); 3.48 (m, ÍH); 3.82 (dd, ÍH); 3.91 (dd, ÍH); 4.12 (overlapping m, 3H); 4.33 (t overlapping, 2H); 4.42 (dd, 2H); 4.97 (d, ÍH); 5.02 (m, 1H); 5.06 (d, ÍH); 6.75 (t, ÍH); 6.87 (d, ÍH); 7.08 (dd, 1H); 7.34 (dd, ÍH); 7.94 (d, ÍH); 8.89 (d, ÍH). MS (ESP): 664 (MH +) for C 26 H 29 C 13 FN 508 Example 18 3- (4- (3 (S) - (2-Methoxyethoxycarbonylamino) pyrrolidin-1-yl) -3-fluorophenyl) -5 (S) - (isoxazole-3 -ylaminomethyl) oxazolidin-2-one. 3- (4- (3 (S) - (2-Methoxyethoxycarbonylamino) pyrrolidin-1-yl) -3-fluorophenyl) -5- (R) - (N- (2, 2, 2-trichloroethyloxycarbonyl) isoxazol-3-ylamethyl) oxazolidin-2-one (400 mg, 0.5 mM) in a mixture of acetic acid (10 ml) and water (2 ml). Zinc powder (203 mg, 3.1 mM) was added and the mixture was stirred 30 minutes at room temperature. The mixture was filtered through celite, and the residue after evaporation was partitioned between ethyl acetate (10 ml) and aqueous sodium bicarbonate (15 ml). The organic phase was washed with sodium bicarbonate (2 x 15 ml), water (15 ml), dried (magnesium sulfate), and evaporated. The crude product was purified by chromatography on a 10 g Biotage silica column, eluting with a gradient from dichloromethane to ethyl acetate. The relevant fractions were combined to give the desired product (141 mg) ..? MR (DMS0-d6) d: 1.83 (hextet, ÍH); 2.09 (hextet, ÍH); 3.13 (m, 1H); 3.26 (s, 3H); 3.40, 3.47 (t overlapping m, 7H); 3.73 (dd, ÍH); 4.04 (overlapping m, 4H); 4.82 (m, ÍH); 6.01 (d, ÍH); 6.52 (t, ÍH); 6.72 (t, ÍH); 7.08 (dd, ÍH); 7.39 (dd, ÍH); 7.52 (d, 1H); 8.37 (d, ÍH). MS (ESP): 464 (MH +) for C2? H26FN50e The 3- (4- (3 (R) - (2-methoxyethoxycarbonylamino) pyrrolidin-1-yl) -3-fluorophenyl) -5 (R) - (N-) (2,2,2-Trichloroethoxycarbonyl) isoxazol-3-ylaminomethyl) oxazolidin-2-one intermediate was prepared as follows: Using essentially the method for the intermediate of Example 12, starting from the hydrochloride salt of 3- (4- (3- (S) -aminopyrrolidin-1-yl) -3-fluorophenyl) -5 (R) - (N- (2,2,2-trichlorotyloxycarbonyl) isoxazol-3-ylaminomethyl) oxazolidin-2-one (419 mg , 0.73 mM) and 2-methoxyethyl chloroformate (450 mg, 3.27 mM) gave the title compound (442 mg). MR (DMSO-d6) d: 1.82 (hextet, ÍH); 2.09 (hextet, ÍH); 3.13 (m, ÍH); 3.23 (s, 3H); 3.27 (m, 1H); 3.39 (m, 1H); 3.46 (t overlapping m, 3H); 3.81 (dd overlapping m, 2H); 4.05 (m, 2H); 4.13 (, 2H); 4.32 (m, ÍH); 4.97 (d, ÍH); 5.02 (m, ÍH); 5.08 (d, ÍH); 6.71 (t, ÍH); 6.88 (d, ÍH); 7.08 (dd, ÍH) 7.34 (dd, ÍH); 7.52 (d, ÍH); 8.89 (d, ÍH). MS (ESP): 638 MH + for C24H27F? 508C13 Example 19: 3- (4- (3 (R) -methoxycarbonylaminopyrrolidin-1-yl) -3-fluorophenyl) -5 (S) - (isoxazol-3-ylaminomethyl) Oxazolidin-2-one The title compound was prepared using essentially the method of Example 11, starting from 3- (4- (3 (R) -methoxycarbonylaminopyrrolidin-1-yl) -3-fluorophenyl) -5 (R) - (N- (2, 2, 2-trichloroethyloxycarbonyl) isoxazol-3-ylaminomethyl) oxazolidin-2-one (1.38 g, 2.32 mM). The residue after the extractive treaty was purified by chromatography on a 20 g Mega Bond Elut® silica column, eluting with a gradient increasing in polarity from 0 100% ethyl acetate in dichloromethane. The relevant fractions were combined and evaporated to give the desired product (490 mg). MR (DMSO-de) d: 1.81 (hextet, ÍH); 2.11 (hextet, 1H); 3.10 (m, 1H); ); 3.24 (m overlapped by H20, ~ 1H); 3.42 (t overlapping m, 3H); 3.50 (s overlapping m, 4H); 3.73 (dd, 1H); 4.07 (t overlapping m, 2H); 4.81 (m, ÍH); 5.98 (d, ÍH); 6.49 (t, ÍH); 6.72 (t, ÍH); 7.08 (dd, ÍH); 7.37 (dd, ÍH); 7.43 (s, 1H); 8.37 (d, ÍH). MS (ESP1: 420 (MH +) for C? 9H22F? 505 Intermediates for this compound were prepared as follows: 3-Fluoro-4- (3 (R) - (-butoxycarbonyl) aminopyrrolidin-1-yl) nitrobenzene 3 was dissolved, 4-Difluoronitrobenzene (16.03 g, 0.101 M) in acetonitrilp (300 ml), and treated with N, N-diisopropylethylamine (32.63 g, 0.253 M) and 3 (R) - (t-butoxycarbonyl) -aminopyrrolidine (20.65 g) , 0.111 M). The mixture was stirred and heated to reflux for 18 hours. The solvent was evaporated, and the residue was treated with ethyl acetate (300 ml) and water (200 ml). The organic layer was washed with water (150 ml), citric acid solution (10% in water, 2 x 150 ml), and dried (magnesium sulfate). Evaporation gave the desired product as a yellow solid (32.7 g) of sufficient quality for use without purification. NMR (DMSO-d3) d: 1.43 (s, 9H); 1.85 (m, ÍH); 2.25 (m, ÍH); 3.44 (dt, ÍH); 3.65 (overlapping m, 2H); 3.84 (dm, ÍH); 4.34 (br, ÍH); 4.69 (br, ÍH); 6.53 (t, ÍH); 7.87 (dd, 1H); 7.92 (dd, ÍH). MS (ESP): 326 (MH +) for C? 5H20FN3O4 5-Amino-2- (3 (R) - (-butoxycarbonyl) aminopyrrolidin-1-yl) fluorobenzene 3-Fluoro-4- (3- (R) was dissolved - (t-butoxycarbonyl) aminopyrrolidin-1-yl) nitrobepcene (32.7 g, 0.101 M) in ethyl acetate (500 ml) was treated with palladium catalyst (10% on carbon, 7.5 g) and hydrogenated at atmospheric pressure until the theoretical incorporation of gas. After filtration through celite and evaporation, the required product was obtained as a red gum of sufficient quality for use without purification (29.85 g). NMR (CDC13) d: 1.44 (s, 9H); 1.82 (m, ÍH); 2.27 (m, ÍH); 3.11 (m, 2H); 3.37 (m, .2H); 3.43 (br, 2H); 4.27 (br m, ÍH); 4.82 (br, ÍH); 6.38 (dd, ÍH); 6.44 (dd, ÍH); 6.57 (t, 1H) .MS (ES P): 296 (MH +) for C, 15H22FN3O2 5-Ethoxycarbonylamino-2 (3 (R) - (t-butoxycarbonyl) -aminopyrrolidin-1-yl) fluorobenzene 5-Amino was dissolved -2- (3- (R) - (t-Butoxycarbonyl) aminopyrrolidin-1-yl) fluorobenzene (27.33 g, 0.093 M) in dry pyridine (150 ml) and cooled under nitrogen with stirring at 0 °. Ethyl chloroformate (11.01, 0.102 M) was added dropwise, and the mixture was stirred 30 minutes at the same temperature. Ice-water (250 ml) was added, and stirring was continued for 1 hour. The resulting precipitate was collected, washed thoroughly with water, and dried, to give the desired product of sufficient quality for use without purification (33.6 g). NMR (DMSO-d6) d: 1.21 (t, 3H); 1.36 (s, 9H); 1.90 (m, ÍH); 2.05 (m, ÍH); 3.04 (m, ÍH); 3.20 (m, ÍH); 3.32 (m, 1H); 3.40 (m, ÍH); 4.02 (br, ÍH); 4.05 (q, 2H); 6.62 (t, 1H); 7.02 (d, ÍH); 7.08 (d, ÍH); 7.22 (d, ÍH); 9.38 (br, 1H) MS (ESP): 368 (MH +) for C? 8H2eFN304 3- (3-Fluoro-4- (3 (R) - (t-butoxycarbonyl) aminopyrrolidin-1-yl) -5 (R) -hydroxymethyloxazolidin-2-one 5-Ethoxycarbonylamino-2 (3 (R) - (t-butoxycarbonyl) aminopyrrolidin-1-yl) fluorobenzene (33.6 g, 0.092 M) was dissolved in dry tetrahydrofuran (300 ml) under nitrogen, cooled at -70 ° and treated by dripping for 30 minutes with a solution of lithium t-butoxide (IM in tetrahydrofuran, 100.7 ml), keeping the temperature low -65 ° C. After stirring for 5 minutes, (R) was added. glycidylbutyrate (14.52 g, 0.101 M), and stirring was continued at -65 ° for 1 hour, before allowing the temperature to rise to room for 16 hours.The mixture was treated with methanol (50 ml), stirred at room temperature environment for 1 hour, and the precipitate was collected and washed well with tetrahydrofuran to give the desired product (21.8 g) NMR (DMSO-d6) d: 1.36 (s, 9H), 1.80 (m, 1H), 2.07 (m , ÍH), 3.09 (m, ÍH), 3.26 (t , 1H), 3.35 (m, ÍH), 3.49 (m, 2H); 3.62 (m, 1H); 3.73 (dd, ÍH); 3.98 (t, ÍH); 4.04 (m, ÍH); 4.63 (m, ÍH); 5.15 (t, ÍH); 6.70 (t, ÍH); 7.09 (dd overlapping br, 2H); 7.39 (dd, ÍH). MS (ESP): 396 (MH +) for C? 9H26FN305 3- (4- (3 (R) - (-Butoxycarbonyl) aminopyrrolidin-1-yl) -3-fluorophenyl) -5 (R) - (N- (2 , 2, 2-trichloroethyloxycarbonyl) isoxazol-3-ylaminomethyl) oxazolidin-2-one The basic method for the intermediate of Example 7, starting from 3- (4- (3 (R) - (t-butoxycarbonyl) aminopyrrolidin- 1-yl) -3-fluorophenyl) -5 (R) -hydroxymethyloxazolidin-2-one (2.0 g, 5.06 mM) was used. The crude product was purified by chromatography on a 90 g Biotage silica column, eluting with a gradient increasing in polarity from 0 to 5% ethyl acetate in dichloromethane. The relevant fractions were combined to give the product desired (1.56 g).

NMR (DMSO-de) d: 1.37 (s, 9H); 1.81 (hextet, 1H); 2. 08 (hextet, ÍH); 3.09 (m, ÍH); 3.25 (m solvent overlap, ÍH); 3.38 (dd, ÍH); 3.48 (t, 1H); 3.82 (dd, ÍH); 4. 04 (m, ÍH); 4.14 (m, 2H); 4.35 (dd, ÍH); 4.97 (d, ÍH); 5.01 (m, ÍH); 5.07 (d, 1H); 6.71 (t, ÍH); 6.88"(d, ÍH); 7.08 (dd, 1 HOUR); 7.11 (br, ÍH); 7.34 (dd, 1H); 8.89 (d, ÍH). MS (ESP): 63 6 (MH +) for C25H29C13FN507, 3- (4- (3 (R) -Aminopyrrolidin-1-yl) -3-fluorophenyl) -5 (R) - (N- (2,2,2-trichloroethyl-oxycarbonyl) isoxazol-3-ylaminomethyl) oxazolidin-2-one Using essentially the method for the intermediate of Example 12, starting from 3- (4- (3 (R 9 - (t-butoxycarbonyl) aminopyrrolidin-1-yl) -3- fluorophenyl) -5 (R) - (N- (2,2,2-trichloroethyloxycarbonyl) isoxazol-3-ylaminomethyl) oxazolidin-2-one (2.18 g, 3.41 mM) gave the hydrochloride salt of the desired product as a white foam ( 1.79 g) • • MR (DMSO-de) d: 2.02 (hextet, ÍH), 2.26 (hextet, ÍH), 3.25 (dd, ÍH), 3.42 (m overlapped by solvent, ÍH), 3.53 (m, 2H) 3.83 (dd overlapping m, 2H), 4.15 (m, 2H), 4.35 (dd, ÍH), 4.98 (d, ÍH), 5.02 (, ÍH), 5.07 (d, ÍH), 6.79 (t, 1H), 6.87 (d, ÍH), 7.12 (dd, ÍH), 7.39 (dd, ÍH), 8.38 (br, 3H), 8.89 (d, 1H) (+1 proton for HCl salt) MS (ESP): 536 (MH +) for C20H2? Cl3F? 5O5 3- (4- (3 (R) -methoxycarbonylaminopyrrolidin-1-yl) -3-fluoro phenyl) -5 (R) - (N- (2,2,2-trichloro-ethyloxycarbonyl) isoxazol-3-ylaminomethyl) oxazolidin-2-one Using essentially the method for the intermediate of Example 12, starting from the salt 3- (4- (3 (R) -aminopyrrolidin-1-yl) -3-fluorophenyl) -5 (R) - (N- (2, 2, 2-trichloroethyloxycarbonyl) isoxazol-3-ylaminomethyl) oxazolidinyl hydrochloride 2-one (1.61 g, 2.81 mM) and methyl chloroformate gave the desired product (1.61 g). MR (DMSO-de) d: 1.82 (hextet, ÍH); 2.11 (hextet, ÍH); 3.13 (m, ÍH); 3.28 (dd, 1H); 3.39 (dd, ÍH); 3.52 (s overlapping m, 4H); 3.82 (dd, ÍH); 4.14 (overlapping m, 3H); 4.36 (dd, ÍH); 4.97 (d, ÍH); 5.03 (m, ÍH); 5.08 (d, ÍH); 6.72 (t, 1H); 6.89 (d, ÍH); 7.08 (dd, ÍH); 7.35 (dd, ÍH); 7.41 (br, ÍH); 8.89 (d, ÍH). MS (ESP): 594 (MH +) for C 22 H 23 Cl 3 F 5 7, Example 20 3- (4- (1- (S), 3-Dihydroxypropanoyl) -1,2,5,6-tetrahydropyrid-4-yl) -3 , 5-difluorophenyl) -5 (S) - (3-methylisoxazol-5-ylaminomethyl) oxazolidin-2-one. 3- (4- (1- (2,2-Diemthyl-1,3-dioxolan-4 ( S) -carbonyl) -1,2,5,6-tetrahydropyrid-4-yl) -3,5-difluorophenyl) -5 (R) - (N- (t-butoxycarbonyl) -3-methylisoxazole-5-ylaminomethyl) oxazolidin-2-one (400 mg7 0.65 mM) in dichloromethane (6 ml) and treated with trifluoroacetic acid (6 ml) at 0 °. After stirring for 30 minutes at room temperature, water (1.2 ml) was added, and stirring was continued for 1 hour. The solvent was removed, the residue was dissolved in methanol (20 ml), and treated with aqueous ammonia to bring the pH to 7-8; the solvent was removed, and the residue was chromatographed on a 10 g Mega Bond Elut® silica column, eluting with a gradient increasing in polarity from 0 to 5% methanol in dichloromethane. The relevant fractions were combined and evaporated to give the desired product (181 mg). NMR (DMSO-d6) d: 2.02 (s, 3H); 2.29 (m, ÍH); 2.35 (m, ÍH); 3.41 (t, 2H); 3.47 (m, ÍH); 3.54 (m, ÍH); 3.71 (m, ÍH); 3.75 (dd, ÍH); 4.04 (dd, 1H); 4.08 (m, ÍH); 4.13 (t, ÍH); 4.24 (m, ÍH); 4.36 (t, ÍH); 4.66 (t, ÍH); 4.82 (, ÍH); 4.95 (t, ÍH); 4.99 (s, ÍH); 5.8S (s, ÍH); 7.30 (d, 2H); 7.36 (t, ÍH). MS (ESP): 479 (MH +) for C22H2 F2 406 Intermediates for this compound were prepared as follows: 3- (4- (l-Benzyl-1,2,5,6-tetrahydropyrid-4-yl) -3, 5-difluorophenyl) -5 (R) -acetoxy-methyloxazolidin-2-one. 3- (4- (1- (Bncyl-1,2,5,6-tetrahydropyrid-4-yl) -3,5-difluorophenyl) was suspended. ) -5- (R) -hydroxy-methyloxazolidin-2-one (20 g, 50 mM, see WO 97-30995) by stirring in dry dichloromethane (400 ml) under nitrogen at 0 °, and treated with triethylamine (5.5 g, 54.4 mM) and 4-dimethylaminopyridine (0.3 g2.7 mM). Acetic anhydride (5.3 g, 0.52 mM) was added dropwise to give a solution, which was stirred for 1 hour, allowing the temperature to rise to room. The mixture was stirred with 5% aqueous sodium bicarbonate (200 ml) until evolution of carbon dioxide ceased. The organic phase was separated, dried (magnesium sulfate) and evaporated, then azeotroped with toluene (2 x 50 ml) to give the semicrystalline product of sufficient purity for the next step (24 g). NMR (DMSO-de) d: 2.03 (s, 3H); 2.30 (br, 2H); 2.61 (t, 2H); 3.04 (m, 2H); 3.58 (s, 2H); 3.82 (dd, ÍH); 4.14 (t, lH); 4.23 (dd, lH); 4.23 (dd, ÍH); 4.30 (dd, 1H) .4.95 (m, ÍH) 5.78 (s, 1 H) 7. 30 (s overlapping m 7 H) MS (ES P): 4 4 3 (MH +) for C24H24F2N204, 3- (4- (1, 2, 5, 6-Tetrahydropyrid-4-yl) -3,5 hydrochloride salt -difluorophenyl) -5 (R) -acetoxymethyloxazolidin-2-one. 3- (4- (1-Benzyl-l, 2,5,6-tetrahydropyrid-4-yl) -3,5-difluorophenyl) -5 ( R) -acetoxy-mtiloxazolidin-2-one (22.1 g, 50 mM) in dry dichloromethane (8.58 g, 60 mM). After stirring for 1 hour the reaction mixture was purified by rapid vacuum agglutination chromatography on 300 g of silica pre-washed with dichloromethane, eluting with a gradient increasing in polarity from 0 to 20% ethyl acetate with dichloromethane . The relevant fractions were combined to give the intermediate chloroethyl carbamate as a gum (20 g). The intermediate was treated immediately with methanol (400 ml) to give a solid, which slowly dissolved under stirring at room temperature for 18 hours. Evaporation of the solvent to a small volume and filtration gave the title product as an off-white solid (14.7 g). NMR (DMSO-d6) d: 2.03 (s, 3H); 2.53 (br 2H); 3.26 (t, 2H); 3.73 (br, 2H); 3.84 (dd, ÍH); 4.16 (t, ÍH); 4.24 (dd, ÍH); 4.30 (dd, ÍH); 4.95 (m, ÍH); 5.88 (s, 1H); 7.37 (d, 2H); 9.39 (s, 2H); (+ 1H for NH2) 3-4- (1- (2, 2-Dimethyl-1,3-dioxolan-4 (S) -ylcarbonyl) -1,2,5,6-tetrahydropyrid-4-yl) -3 , 5-difluorophenyl) -5 (R) -acetoxymethyloxazolidin-2-one. 3- (4- (1, 2, 5,6,6-tetrahydropyrid-4-yl) -3,5-difluorophenyl) -5 hydrochloride was suspended. R) -acetoxymethyloxaolidin-2-one (14.5 g, 37.3 M) in dry dichloromethane (300 ml) under nitrogen at 0 °, and treated with pyridine (9.78 g, 0.12 M). A solution of 2,2-dimethyl-1,3-dioxolan-4 (S) -ylcarbonyl chloride (9.59 g, 75.6 M) in dichloromethane (100 ml) was added dropwise, and the stirring continued for 3 hours, allowing raise the temperature to the environment. Aqueous sodium bicarbonate (5%, 300 ml) was added, and stirring continued for 30 minutes. The organic phase was separated, dried (magnesium sulfate), filtered and evaporated to dryness after addition of toluene (20 ml). The solid residue was triturated with a mixture of diethyl ether (250 ml) and isohexane (150 ml), and the solid was filtered to give the compound (17.5 g).

NMR (DMSO-de) d: 1.30 (2 x s, 6H); 2.02 (s, 3H); 2. 28 (br, ÍH); 2.39 (br, ÍH); 3.67 (t overlapping m, 2H); 3. 83 (dd, ÍH); 4.00-4.32 (overlapping m, 7H); 4.90 (overlapping m, 2H); 5.86 (s, ÍH); 7.34 (d, 2H). MS (ESP): 481 (MH +) for C23H26F2N2.07 3- (4- (l- (2,2-Dimethyl-l, 3-dioxolan-4 (S) -ylcarbonyl) -1,2,5,6- tetrahydropyrid-4-yl) -3,5-difluorophenyl) -5 (R) -hydroxymethyloxazolidin-2-one. 3- (4- (1- (2,2-dimethyl-1,3-dioxolan-4 (S) was suspended. ) -carbonyl) -1,2,5,6-tetrahydropyrid-4-yl) -3,5-difluorophenyl) -5 (R) -acetoxymethyloxazolidin-2-one (8.64 g, 18 mM) in methanol (350 ml) and stirred at room temperature under nitrogen. Potassium carbonate (3.73 g, 27 mM) was added and the mixture was stirred for 20 minutes only, then immediately neutralized by the addition of acetic acid (2 ml). Saturated aqueous sodium bicarbonate (50 ml) was added, the methanol was evaporated, and the residue was diluted with water (100 ml) before extraction of the organics in dichloromethane (250 ml + 100 ml). The extract was washed with brine (100 ml), dried (magnesium sulfate), evaporated and the product was not purified, purified by chromatography on a silica vacuum binder column, eluting with a gradient from 0% to 20% of methanol in dichloromethane. The relevant fractions were combined to give the desired product (7.3 g).

NMR (DMSO-de) d: 1.29 (s, 3H); 1.32 (s, 3H); 2. 29 (br, lH); 2.38 (br, ÍH); 3.48-3.76 (m complex, 4H); 3.82 (dd, ÍH); 4.05 (m complex, 4H); 4.21 (dd, lH); 4.72 (m, 1H); 4. 90 (dd, ÍH); 5.22 (t, lH); 5.86 (s, ÍH); 7.35 (d, 2H). MS (ESP): 439 (MH +) for C21H24F2N206 3- (4- (1- (2,2-dimethyl-l, 3-dioxolan-4 (S) -ylcarbonyl) -1,2,5,6-tetrahydropyrid- 4-yl) -3,5-difluorophenyl) -5 (R) -methanesulfonyloxymethyloxazolidin-2-one. 3- (4- (1- (2, 2-Dimethyl-1,3-dioxolan-4 (S) - was dissolved. ilcarbonyl) -1, 2, 5, 6-tetrahydropyrid-4-yl) -3,5-difluorophenyl) -5 (R) -hydroxymethyloxazolidin-2-one (2.19 g, 5 mM) in dry dichloromethane (40 ml) under nitrogen at 0 ° C, and treated with triethylamine (0.81 g8 mM). Methanesulfonyl chloride (0.687 g, 6mM) was added and stirring continued for 2 hours, allowing room temperature to rise. Aqueous sodium bicarbonate (5%, 20 ml) was added, and stirring continued for 10 minutes. The organic phase was separated, dried (magnesium sulfate), filtered and evaporated to dryness. The resulting gum was triturated with diethyl ether (50 ml) and the solid was filtered to give the title compound (2.4 g). NMR (DMSO-de) d: 1.30 (s, 3H); 1.33 (s, 3H); 2.30 (br, 1H); 2.39 (br, ÍH); 3.26 (s, 3H) 3.67 (t overlapping m, 2H); 3.82 (dd, ÍH); 4.01-4, 31 (overlapping complex of m, 5H); 4.45 (dd, ÍH); 4.51 (dd, ÍH). 4.90 (dd, ÍH); 5.03 (, ÍH) 5.87 (s, ÍH); 7.35 (d, 2H). MS (ESP): 517 (MH +) for C22H26F2N208S 3- (4- (1- (2, 2-Dimethyl-1,3-dioxolan-4 (S) -ylcarbonyl) -1,2,5,6-tetrahydropyrid-4-yl) -3,5-difluorophenyl ) -5 (R) - (N- (t-butoxycarbonyl) -3-methylisoxazol-5-ylaminomethyl) oxazolidin-2-one Sodium hydride (60% in oil, 72 mg, 1.8 mM) was suspended in N, N Dried dimethylformamide (3 ml), cooled to 0 ° under nitrogen, and a solution of 5- (t-butoxycarbonylamino) -3-methylisoxazole (356 mg, 1.8 mM) in N, N-dimethylformamide (3 ml) was added. . After stirring for 10 minutes, a solution of 3- (4- (1- (2,2-dimethyl-1,3-dioxolan-4 (S) -ylcarbonyl) -1,2,5,6-tetrahydropyrid was added. -4-yl) -3,5-difluorophenyl) -5 (R) -metanesulfonyloxymethyloxazolidin-2-one (516 mg, 1.5 mM) in N, N-dimethylformamide (3 ml), and the mixture was heated at 40 ° C for 5 hours. After cooling, the mixture was poured into water (50 ml), taken up in dichloromethane (4 x 20 ml). The organic phase was dried (magnesium sulfate), evaporated and the crude product was purified by chromatography on a 10 g Mega Bond Elut® silica column, eluting with a gradient of 50% to 75%, of ethyl acetate in isohexane. The relevant fractions were combined to give the desired product (420 mg). MR (DMSO-de) d6: 1.30 (s, 3H); 1.32 (s, 3H); 1.46 (s, 9H); 2.18 (s, 3H); 2.30 (m, ÍH); 2.41 (iti, ÍH); 3.67 (t, 1H); 3.74 (m, ÍH); 3.81 (dd, ÍH); 4.00 (overlapping m, 3H); 4.06 (dd, ÍH); 4.18 (m, 3H); 4.89 (m, 2H); 5.87 (s, ÍH); 6.04 (s, ÍH); 7.31 (d, 2H). MS (ESP): 619 (MH +) for C3oH36F2N408 5- (t-butoxycarbonylamino) -3-methylisoxazole 5-Amino-3-methylisoxazole was dissolved (4.91 g, 0.05 M) in dry dichloromethane (80 ml) and 4-dimethylaminopyridine (100 mg) and di-t-butyl dicarbonate (21.85 g, 0.1 mg) was added.

M) The mixture was stirred at room temperature for 48 hours, then evaporated to dryness. The residue was purified by chromatography on a 90 g Biotage silica column, eluting with a gradient increasing in polarity from 0 to 5% diethyl ether in dichloromethane. The relevant fractions were combined and evaporated to give the desired product (0.67 g). NMR (DMSO-de) d: 1.46 (s, 9H); 2.12 (s, 3H); 5.81 (s, ÍH); 10.85 (br, ÍH). MS (ESP) .199 (MH) for C9H? 4N203 Example 21: 3- (4- (1- (2 (S), 3-Dihydroxypropanoyl) -1, 2, 5, 6-tetrahydropyrid-4-yl) - 3,5-di-luo-phenyl) -5 (S) - (1,2,4-thiadiazol-5-ylaminomethyl) oxazolidin-2-one Using essentially the conditions of Example 20, but starting from 3- (4- ( 1- (2,2-dimethyl-1,3-dioxolan-4 (S) -ylcarbonyl) -1,2,5,6-tetrahydropyrid-4-yl) -3,5-difluorophenyl) -5 (R) - (N- (t-butoxycarbonyl) -l, 2,4-thiadiazol-5-ylaminomethyl) oxazolidin-2-one (200 mg, 0.3 mM) gave the title product (91 mg). NMR (DMSO-de) d: 2.31 (, 1H); 2.37 (m, ÍH); 3.47 (m, 1H); 3.55 (m, ÍH); 3.71 (m, 4H); 3.79 (dd, ÍH); 4.10 (, ÍH); 4.16 (t, ÍH); 4.26 (m, ÍH); 4.35 (t, ÍH); 4.66 (t, ÍH); 4.93 (m, 2H); 5.85 (s, ÍH); 7.31 (d, 2H); 7.92 (s, 1H); 8.72 (br, 1H). MS (ESP): 482 (MH +) for C2oH2? F2N5? 5S Intermediates for this compound were prepared as follows: 3- (4- (1- (2, 2-Dimethyl-1,3-dioxolan-4 (S) -carbonyl) -1,2,5,6-tetrahydropyrid-4-yl) -3,5-difluorophenyl) -5 (R) - (N- (t-butoxycarbonyl) -1,2,4-thiadiazole-5- ilaminomethyl) oxazolidin-2-one Using essentially the technique of the relevant intermediate for Example 20 but using 5- (t-butoxycarbonylamino) -1,2,4-thiadiazole (330 mg, 1.5 mM) as the amino component gave the product of the title (221 mg). MR (DMSO-de) d: 1.30 (s, 3H); 1.33 (s, 3H); 1.53 (s, 9H); 2.31 (m, ÍH); 2.39 (m, ÍH); 3.67 (t, 1H); 3.75 (m, ÍH); 3.94 (dd, ÍH); 4.08 (t overlapping m, 2H); 4.23 (t overlapping m, 3H); 4.30 (dd, ÍH); 4.46 (dd, ÍH); 4.96 (dd, ÍH); 5.07 (m, ÍH); 5.87 (s, ÍH); 7.33 (d, 2H); 8.43 (s, ÍH). MS (ESP): 622 (MH +) for C28H33F2? 507S 5- (-butoxycarbonylamino) -1,2, -thiadiazole 5-Amino-1,2,4-thiadiazole hydrochloride (1.38 g, 0.01 M) was suspended by stirring in dry dichloromethane (50 ml), triethylamine (1.21 g, 0.012M) was added, and the mixture was stirred at room temperature for 20 minutes to give a solution. Di-t-butyl dicarbonate (4.8 g, 0.022 M) was added and the mixture was stirred at room temperature for 18 hours, then evaporated to dryness. The residue was purified by chromatography on a 20 g Mega Bond Elut® silica column, eluting with a gradient from 0% to 10% diethyl ether in dichloromethane. The relevant fractions were combined to give the desired product (1.05 g). NMR (DMSO-d6) d: 1.50 (s, 9H); 8.33 (s, 1H); 12.31 (br, 1H) .MS (ESP): 202 (MH +) for C7H ?? N302S Example 22: 3- (4- (1- (2 (S), 3-Dihydroxypropanoyl) -1, 2, 5, 6 -tetrahydropyrid-4-yl) -3,5-di luoro-enyl) -5 (S) -pyrazin-2-ylaminomethyloxazolidin-2-one. 3- (4- (1- (2, 2-dimethyl-1, 3-dioxolan-4 (S) -ylcarbonyl) -1,2,5,6-tetrahydropyrid-4-yl) -3,5-difluorophenyl) -5 (R) - (N- (-butoxycarbonyl) pyrazin-2-) ilaminomethyl) oxazolidin-2-one (400 mg, 0.65 M) in dichloromethane (4 ml) and treated with trifluoroacetic acid (4 ml) at room temperature. After stirring for 30 minutes at room temperature, water (0.8 ml) was added, and stirring continued for 2 hours. The solvent was removed, the residue was dissolved in methanol (20 ml), and treated with aqueous ammonia to bring the pH to 8; the solvent was removed, and the residue was chromatographed on a 10 g Mega Bond Elut® silica column, eluting with a gradient increasing in polarity from 5 to 10% methanol in dichloromethane. The relevant fractions were combined and evaporated to give the desired product (315 mg). NMR (DMSO-dβ) d: 2.28 (br, 1H); 2.37 (br, ÍH); 3.46 (m, ÍH); 3.54 (m, ÍH); 3.64 (t, 2H); 3.71 (m, ÍH); 3.81 (dd, ÍH); 4.10 (overlapping m, 4H); 4.36 (m, ÍH); 4.71 (t, ÍH); 4.89 (m, ÍH); 5.01 (t, ÍH); 5.85 (s, 1H); 7.32 (d, 2H); 7.43 (t, ÍH); 7.70 (d, ÍH); 7.94 (d, ÍH); 7.99 (s, ÍH). MS (ESP): 476 (MH +) for C22H23F2N505 Intermediates for this compound were prepared as follows: 3- (4- (1- (2, 2-Dimethyl-1,3-dioxolan-4 (S) -ylcarbonyl) - 1,2,5,6-tetrahydropyrid-4-yl) -3,5-difluorophenyl) -5 (R) - (A7- (t-butoxycarbonyl) pyrazin-2-ylaminomethyl) oxazolidin-2-one Hydride was suspended from sodium (50% in oil, 72 mg, 1.5 mM) in dry N, N-dimethylformamide (3 ml) under nitrogen, and a solution of t-butoxycarbonylaminopyrazine (293 mg, 1.5 mM) in N, N-dimethylformamide was added. (3 ml). After stirring for 10 minutes, a solution of 3- (4- (1- (2, 2-diemethyl-l, 3-dioxolan-4 (S) -ylcarbonyl) -1,2,5,6-tetrahydropyrid was added. -4-yl) -3,5-difluorophenyl) -5 (R) -methanesulfonyloxymethyloxazolidin-2-one (516 mg, 1.5 mM, Example 20) in N, N-dimethyl formamide (3 ml), and the mixture was heated at 40 ° for 2.5 hours. After cooling, the mixture was diluted with aqueous sodium bicarbonate (5%, 30 ml), recovered in ethyl acetate (2 x 30 ml) The organic phase was washed with water (10 ml) and brine (10 ml) , dried (magnesium sulfate), evaporated and the crude product was purified by chromatography on a 10 g silica column, Mega Bond Elut®, eluting with a gradient from 0% to 60% ethyl acetate in dichloromethane. . The relevant fractions were combined to give the desired product (450 mg). NMR (DMSO-de) d: 1.30 (s, 3H); 1.33 (s, 3H); 1.45 (s, 9H); 2.28 (br, ÍH); 2.39 (br, ÍH); 3.67 (t, ÍH); 3.75 (m, ÍH); 3.87 (dd, ÍH); 4.02-4.25 (overlapping m, 6H); 4.32 (dd, ÍH); 4.90 (dd, ÍH); 5.01 (m, ÍH); 5.87 (s, 1H); 7.33 (d, 2H); 8.37 (d, 1H); 8.44 (d, ÍH); 8.91 (s, 1H). MS (ESP): 616 (MH +) for C30ri35 F2N5O7 t-Butoxycarbonylaminopyrazine Aminopyrazine (3 g, 31.6 mM) was dissolved in dry dichloromethane (100 ml), and 4-dimethylaminopyridine (200 mg) and di-t-dicarbonate was added. butyl (14 g, 64. Z mM). The mixture was stirred at room temperature for 18 hours, then evaporated to dryness. The residue was purified by chromatography on a 50 g Isolute silica column, eluting with dichloromethane. The relevant fractions were combined and evaporated to give di- (t-butoxycarbonyl) aminopyrazine (2.4 g).

NMR (DMSO-de) d: 1.36 (s, 18H); 8.55 (d, ÍH); 8.58 (d, ÍH); 8.73 (s, 1H). MS (ESP): 296 (MH +) for Ci4H2? N304 Di- (t-Butoxycarbonyl) aminopyrazine (2.1 g, 7.1 mM) in methanol (50 ml) was treated under nitrogen with aqueous sodium hydroxide (2.5 M, 2.84 ml. , 7.1 mM) and stirred at room temperature for 2 hours. The mixture was neutralized by the addition of water (25 ml) and solid carbon dioxide, then evaporated with methanol. The residual aqueous solution was taken up in dichloromethane (2 x 20 ml), the extracts were washed with brine (20 ml) and evaporated. The resulting solid was triturated with isohexane (50 ml) to give the title product as a white solid (1.03 g). NMR (DMSO-d6) d: 1.47 (s, 9H); 8.25 (d, ÍH); 8.30 (d, ÍH); 9.03 (s, ÍH); 10.14 (s, ÍH). MS (ESP): 196 (MH +) for CH13N302 Example 23: 3- (4- (1- (2 (S), 3-Dihydroxypropanoyl) -1, 2, 5, 6-tetrahiropyrid-4-yl) -3, 5-difluorophenyl) -5 (S) -pyrimidin-2-ylaminome-ioxazolidin-2-one Using essentially the technique of Example 22, but starting from 3- (4- (1- (2, 2-dimethyl-1, 3-dioxolan-4 (S) -ylcarbonyl) -1,2,5,6-tetrahydropyrid-4-yl) -3,5-difluorophenyl) -5 (R) - (N- (t-butoxycarbonyl) pyrimidin-2) -ylaminomethyl) -oxazolidin-2-one (400 mg, 0.65 mM), gave the title product (284 mg) after chromatography. MR (DMSO-de) d: 2.29 (br, .IH); 2.38 (br, ÍH); 3.47 (m, ÍH); 3.54 (m, ÍH); 3.61 (m, 3H); 3.72 (m, ÍH); 3.85 (dd, ÍH); 4.13 (t overlapping m, 3H); 4.36 (m, ÍH); 4.70 (t, ÍH); 4.88 (m, ÍH); 4.99 (t, 1H); 5.85 (s, ÍH); 6.61 (t, ÍH); 7.32 (d, 2H); 7.44 (t, ÍH); 8.28 (d, 2H). MS (ESP): 476 (MH +) for C22H23F2N5? 5 Intermediates for this compound were prepared as follows: 3- (4- (1- (2, 2-Dimethyl-1,3-dioxolan-4 (S) -ylcarbonyl ) -1,2,5,6-tetrahydropyrid-4-yl) -3,5-difluorophenyl) -5 (R) - (N- (t-butoxycarbonyl) pyrimidin-2-ylaminomethyl) oxazolidin-2-one Was used essentially the technique for the appropriate intermediate of Example 22, but substituting 2- (t-butoxycarbonylamino) pyrimidine (293 mg, 1.5 mM) for the pyrazine analogue. To complete the reaction, it was necessary to heat at 80 ° for 1 hour, and chromatography was carried out with a gradient from 0% to 50% ethyl acetate in dichloromethane containing 2% triethylamine. The relevant fractions were combined to give the desired product (427mg). MR (DMS0-d6) d: 1.32 (s, 3H); 1.34 (s, 3H); 1.41 (s, 9H) 2.30 (br, ÍH); 2.38 (br, ÍH); 3.67 (t, ÍH); 3.75 (m, ÍH) 3.87 (dd, 1H); 4.00-4.33 (overlapping m, 7h); 4.90 (dd, lh) 5.01 (m, ÍH); 5.87 (s, ÍH); 7.27 (t, ÍH); 7.31 (d, 2H); 8.73 (d, 2H). MS (ESP): 616 (MH +) C3oH35F2? 507 2- (t-Butoxycarbonylamino) irimidine The technique was essentially used for the appropriate intermediate of Example 22, but substituting 2-aminopyridimidine (3 g, 21.6 mM) for aminopyrazine. The reaction was stirred for 72 hours and the chromatography used a gradient of 0 to 10% diethyl ether in dichloromethane; the product was finally triturated with isohexane (10 ml) to give 2- (di- (t-butoxycarbonyl) amino) pyrimidine (5.7 g) NMR (DMSO-d6) d: 1.37 (s, 18H); 7.48 (t, 1H); 8.66 (d, 2H). MS (ESP): 296 (MH +) for Ci4H2? N304 2- (Di- (t-butoxycarbonyl) amino) -pyrimidine (5.2 g, 17.6 M) was hydrolyzed essentially by the technique for the appropriate intermediate of Example 22 to give the product of the title as a white solid (3.2 g). NMR (DMSO-d6) d: 1.43 (s, 9H); 7.08 (t, ÍH); 8.57 (d, 2H); 9.91 (s, ÍH). MS (ESP): 196 (MH *) for C9H? 3N302Example 24: 3- (4- (1- (2 (S), 3-Dihydroxypropanoyl) -1,2,5, 6-te rahidropi id-4-il ) -3,5-difluorophenyl) -5 (S) -pyridazin-3-ylaminomethyloxazolidin-2-one Using essentially the technique of Example 22, but starting from 3- (4- (1- (2, 2-dimethyl) -l, 3-dioxolan-4 (S) -ylcarbonyl) -1,2,5,6-tetrahydropyrid-4-yl) -3,5-difluoro-phenyl) -5 (R) - (? 7- (t -butoxycarbonyl) pyridazin-3-ylaminomethyl) -oxazolidin-2-one (300 mg, 0.49 mM), gave the title product (217 mg) after chromatography. NMR (DMSO-de) d: 2.29 (br, 1H); 2.39 (br, ÍH); 3.47 (m, ÍH); 3.55 (m, ÍH); 3.74 (t overlapping m, 4H); 3.83 (dd, 1H); 4.16 (t overlapping m, 3H); 4.35 (m, ÍH); 4.66 (m, 1H); 4.94 (m, 2H); 5.85 (s, ÍH); 6.85 (d, ÍH); 7.15 (t, 1H); 7.22 (dd, ÍH); 7.30 (d, 2H); 8.44 (d, ÍH). MS (ESP): 476 (MH +) for C22H23F2N5OS5 Intermediates for this compound were prepared as follows: 3- (4- (1- (2, 2-Dimethyl-1,3-dioxolan-4 (S) -ylcarbonyl) - 1,2,5,6-tetrahydropyrid-4-yl) -3,5-difluorophenyl) -5 (R) - (N- (t-butoxycarbonyl) pyridazin-3-ylaminomethyl) oxazolidin-2-one. technique for the appropriate intermediate of Example 22, but substituting 3- (t-butoxycarbonylamino) pyridazine (293 mg, 1.5 mM) for the pyrazine analogue. The reaction was carried out by heating at 45 ° for 4 hours, and chromatography was carried out with a gradient from 0% to 100% ethyl acetate in dichloromethane. The relevant fractions were combined to give the desired product (315 mg). MR (DMSO-de) d: 1.17 (s, 3H); 1.20 (s, 3H); 1.33 (s, 9H); 2.16 (br, ÍH); 2.25 (br, ÍH); 3.55 (t, ÍH); 3.62 (t, ÍH); 3.76 (dd, ÍH); 3.84-4.17 (overlapping m, 6H); 4.30 (dd, ÍH); 4.77 (dd, ÍH); 4.96 (m, ÍH); 5.84 (s, 1H); 7.19 (d, 2H); 7.55 (dd, ÍH); 7.78 (d, ÍH); 8.89 (d, ÍH). MS (ESP): 616 (MH +) for C3oH35F2? 507, 3- (t-Butoxycarbonylamino) pyridazine The technique was essentially used for the appropriate intermediate of Example 22, but substituting 3-aminopyridazine (1.3 g, 13.6 mM) for aminopyrazine. The reaction was stirred for 18 hours and chromatography used a gradient of 0 to 20% diethyl ether in dichloromethane to give 3- (di- (t-butoxycarbonyl) amino) pyridazine (1.2 g). NMR (DMSO-d6) d: 1.37 (s, 18H); 7.82 (d, 2H); 9.18 (t, ÍH). MS (ESP): 296 (MH +) for C? 4H2? N304 2- (Di- (t-butoxycarbonyl) amino) -pyrimidine (5.2 g, 17.6 mM) was hydrolyzed by essentially the technique for the appropriate intermediate of Example 22, to give the title product as a white solid (690 mg). NMR (DMSO-de) d: 1.47 (s, 9H); 7.60 (dd, ÍH); 8.04 (d, ÍH); 8.87 (d, ÍH); 10.41 (s, 1H). MS (ESP): 196 (MH +) for C9H13N302 Example 25: 3- (4- (1-Acetoxyacetyl-l, 2,5,6-tetra-idropyrid-4-yl) -3,5-difluoro-enyl) -5 ( S) - (1,2,5-thiadiazol-3-ylaminomethyl) -oxazolidin-2-one Trifluoroacetic acid (5 ml) was added dropwise to a stirred solution of 3- (4- (1-acetoxyacetyl-2). , 5,6-tetrahydropyrid-4-yl) -3,5-difluorophenyl) -5 (R) - (N- (t-butoxy-carbonyl) -1,2,5-thiadiazol-3-ylaminomethyl) oxazolidin-2 -one (426 mg, 0.718 mM) in dichloromethane (10 ml) and the mixture was maintained for one hour. The solution was washed with water, saturated sodium bicarbonate solution and brine and dried (sodium sulfate). The solvent was evaporated and the residue was purified on a Mega Bond Elut® silica column, eluting with dichloromethane, and then 1.5% methanol / dichloromethane to give an oil which was solidified in trituration with cold diethyl ether to give the title product. (254 mg, 72%). NMR (DMSO-d6) d: 2.08 (s, 3H); 2.31 (m, ÍH); 2.40 (m, ÍH); 3.53 (t, ÍH); 3.63 (.3H); 3.82 (dd, ÍH); 4.07 (m, 2H); 4.17 (t, ÍH); 4.82 (d, 2H); 4.95 (m, ÍH); 5.85 (m, 1H); 7.32 (d, 2H); 7.71 (t, ÍH); 8.41 (s, 1H); MS (ESP): 495 (MH *) for C2? H2? F2N505S Intermediates for this compound were prepared as follows: 3- (4- (1-Benzyl-l, 2,5,6-tetrahydropyrid-4-yl) -3,5-difluorophenyl) -5 (R) - (N- (t-butoxycarbonyl) -1,2,5-thiadiazol-3-ylaminomethyl) oxazolidin-2-one - 1,1'- ( Azodicarbonyl) dipiperidine (680 mg, 2.7 mM) to a stirred solution of 3-t-butyloxycarbonylamino-1, 2, 5-thiadiazole (543 mg, 2.7 mM, see WO 93-13091), 3- (4- (1- benzyl-l, 2,5,6-tetrahydropyrid-4-yl) -3,5-difluorophenyl) -5 (R) -hydroxy-methyloxazolidin-2-one (720 mg, 1.8 mM; prepared by analogy with compound 3 Fluoro-see WO 97-30995) and tributylphosphine (540 mg, 2.7 M) in dry tetrahydrofuran (25 ml) at 0 ° under nitrogen. The mixture was stirred at 0 ° for 30 minutes and then at room temperature for 3 hours. The mixture was filtered and the filtrate was evaporated. The residue was purified, firstly on a Mega Bond Elut® silica column, eluting with a gradient increasing in polarity from 0 to 30% ethyl acetate in isohexane and then in an SCX Isolute ion exchange column, washing with a gradient increasing in polarity from 0 to 10% methanol in dichloromethane and then eluting with dichloromethane / methanol / ammonia 0.88SG 87: 10: 3 to give the title product as a solid (669 mg, 64%). NMR (DMSO-de) d: 1. 49 (s, 9H); 2.30 (brs, 2H); 2.61 (t, 2H); 3.04 (m, 2H); 3.58 (s, 2H); 3.88 (dd, ÍH); 4.13 (dd, ÍH); 4.20 (dd, ÍH); 4.35 (dd, ÍH); 5.02 (m, 1H); 5.79 (brs, ÍH); 7.20-7.33 (m, 7H); 8.96 (s, ÍH). MS (ESP): 584 (MH +) for C29H3? F2N504S 3- (4- (1, 2, 5, 6-Tetrahydropyrid-4-yl) -3,5-difluorophenyl) -5 (R) - (N) hydrochloride - (t-butoxycarbonyl) -1,2,5-thiadiazol-3-ylaminomethyl) oxazolidin-2-one Using the method described for the appropriate intermediate of Example 20, apart from the routine changes in the eluent used for chromatography, hydrolyzing the intermediate carbamate by refluxing 1 hour in methanol, and starting from 3- (4- (1-benzyl-l, 2,5,6-tetrahydropyrid-4-yl) -3,5-difluorophenyl) -5 (R ) - (N- (t-butoxycarbonyl) -1,2,5-thiadiazol-3-ylaminomethyl) oxazolidin-2-one (650 mg, 1.0 mmol) gave the title compound (493 mg, 84%). MR (DMSO-d6) d: 1.54 (s, 9H); 2.52 (m overlapped by DMSO, 2H); 3.28 (m overlapped by H20, 2H); 3.76 (s, 2H); 3.91 (dd, ÍH); 4.12-4.25 (m, 2H); 4.40 (dd, ÍH); 5.09 (m ÍH); 5.91 (s, ÍH); 7.40 (d, 2H); 9.00 (s, ÍH); 9.25 (brs, 2H); (+ ÍH for the HCl salt). MS (ESP): 494 for C22H25F2N5? 4S 3- (4- (1-Acetoxyacetyl-l, 2,5,6-tetrahydropyrid-4-yl) -3,5-difluorophenyl) -5 (R) - (N-) (-butoxycarbonyl) -l, 2,5-thiadiazol-3-ylaminomethyl) oxazolidin-2-one. 3- (4- (1, 2, 5, 5,6-tetrahydropyrid-4-yl) -3,5 hydrochloride was suspended. -difluorophenyl) -5 (R) -. { N- (-butoxycarbonyl) -12, 5-thiadiazol-3-ylaminomethyl) oxazolidin-2-one (485 mg, 0.916 mM) in a mixture of acetone (10 ml) and water (5 ml), and sodium bicarbonate (770 mg, 9.2 mg) was added. mM). The mixture was cooled in an ice bath and treated by dripping with acetoxyacetyl chloride (495 mg, 3.63 mM), and then stirred for 7 hours allowing the temperature to rise to room temperature. Additional portions of sodium bicarbonate (770 mg) and acetoxyacetyl chloride (495 mg) were added, and stirring continued for 18 hours. The mixture was diluted with water (20 ml) and taken up in ethyl acetate (3 x 25 ml), and the combined organics were washed with water (2 x 15 ml), aqueous hydrochloric acid (IM, 15 ml), brine (15 ml) and dried (sodium sulfate) to give the desired product (434 mg, 80%). ? MR (400 MHz, DMSQ-d6) d: 1.50 (s, 9H); 2.10 (s, 3H); 2.31 (m, 1H); 2.42 (m, ÍH); 3.57 (t, ÍH); 3.66 (t, ÍH); 3. 90 (dd, ÍH); 4.04-4.22 (m, 4H); 4.39 (dd, ÍH); 4.85 (d, 2H); 5.08 (, ÍH); 5.88 (s, ÍH); 7.35 (d, 2H); 9.00 (s, ÍH). MS (ESP): 594 (MH *) for C 26 H 29 F 2 N 507 S Example 26: 3- (4- (1-Hydroxyacetyl-l, 2,5,6-tetrahydropyrid-4-yl) -3,5-di-chlorophenyl) -5 ( S) - (1, 2, 5-thiadiazol-3-ylaminomethyl) -oxazolidin-2-one A saturated solution of ammonia in methanol (7 ml) was added to a suspension of 3- (4- (1-acetoxyacetyl-1) , 2, 5, 6-tetrahydropyrid-4-yl) -3,5-difluorophenyl) -5 (S) - (1,2,5-thiadiazol-3-ylaminomethyl) oxazolidin-2-one (228 mg, 0.462 mM , Example 25), in methanol (7 ml) and the mixture was stirred for 20 hours. A small amount of insoluble material was filtered and the filtrate was evaporated to a small volume and cooled. The precipitate was filtered and washed with cold methanol and diethylether to give the title product (150 mg, 72%). NMR (400 MHz, DMSQ-d6) d: 2.23 (m, 1H); 2.30 (m, 1H); 3.46 (t, ÍH); 3.62 (m, 3H); 3.79 (dd, ÍH); 3.97-4.12 (m, 5H); 4.52 (dt, ÍH); 4.90 (m, ÍH); 5.80 (m, 1H); 7.32 (d, 2H); 7.63 (t, ÍH); 7.97 (s, ÍH). MS (ESP): 452 (MH +) for C? 9H? 9F2N504S Example 27: 3- (4- (1- (2 (S) 3, -Dihydroxypropanoyl) -1, 2, 5, 6-tetrahydropyrid-4-yl ) -3-fluorophenyl) -5 (S) - (1,2,5-thiadiazol-3-ylaminomethyl) oxazolidin-2-one A solution of .3- (4- (1- (2, 2-dimethyl-1) , 3-dioxolan-4 (S) -ylcarbonyl) -1,2,5,6-tetrahydropyrid-4-yl) -3-fluoro-phenyl) -5 (R) - (N- (t-butoxycarbonyl) -1 , 2,5-thiadiazol-3-ylamino-methyl) oxazolidin-2-one (580 mg, 0.96 mM) in trifluoroacetic acid (2 ml) was heated at 60 ° for 2 minutes and then kept at room temperature for 10 minutes . A solution of trifluoroacetic acid in water (10 ml 1: 1) was added and the mixture was maintained for 30 minutes. More trifluoroacetic acid (2 ml) was added and then an additional 90 minutes, excess aqueous ammonia was added and the mixture was recovered three times with ethyl acetate. The combined extracts were washed with water, sodium bicarbonate solution and brine and dried (sodium sulfate). The solvent was evaporated and the residue was purified on a Mega Bond Elut® silica column, eluting with dichloromethane and then 4% methanol in dichloromethane to give an oil which solidified in trituration with diethylether to give the title product (203 mg , 46%). MR (400 MHz, DMSO-d6 / CD3COOD) d: 2.41 (m overlapping DMSO, 2H); 3.45 (m, ÍH); 3.54 (m, ÍH); 3.48 (overlapping m, 4H); 3.82 (dd, 1H); 4.08-4.25 (m, 3H); 4.39 (m, ÍH); 4.92 (, ÍH); 6.01 (s, ÍH); 7.27 (dd, ÍH); 7.32 (t, ÍH); 7.45 (dd, ÍH); 8.01 (s, ÍH); 2 x OH, 1 x? H absent, exchanged. MS (ESP): 464 (MH *) for C20H22F? 505S The intermediate was prepared as follows: Using the methods of the sequence described for the intermediates for Example 25, but starting from 3- (4- (1-benzyl) -l, 2, 5, 6-tetrahydropyrid-4-yl) -3-fluorophenyl) -5 (R) -hydroxymethyl-oxazolidin-2-one (1.5 g, 3.93 mM, see WO 97-30995) gave the product of the title (1.77 g, 80%). NMR (DMSO-d6) d: 1.50 (s, 9H); 2.42 (brs, 2H); 2.61 (t, 2H); 3.05 (m, 2H); 3.56 (s, 2H); 3.87 (dd, ÍH); 4.14 (dd, ÍH); 4.21 (dd, ÍH); 4.36 (dd, ÍH); 5.02 (m, ÍH); 5.95 (s, ÍH); 7.21-7.46 (overlapping m, 8H); 8.95 (s, 1H). MS (ESP): 566 (MH *) for C29H32FN504S 3- (4- (1, 2, 5, 6-Tetrahydropyrid-4-yl) -3-fluorophenyl) -5 (R) - (N- (t -butoxycarbonyl) -l, 2,5-thiadiazol-3-ylaminomethyl) oxazolidin-2-one Using the methods of the sequence described by the intermediates for Example 25, but starting from 3- (4- (1-benzyl -l, 2,5,6-tetrahydropyrid-4-yl) -3-fluorophenyl) -5 (R) - (N- (t-butoxycarbonyl) -1,2,5-thiadiazol-3-ylaminomethyl) -oxazolidin- 2-one (1.72 g, 3.04 mM) gave the title product (1.1 g, 71%). MR (DMSO-de) d: 1.51 (s, 9H); 2.64 (m, 2H); 3.28 (m overlapped by H20, 2H); 3.75 (s, 2H); 3.91 (dd, ÍH); 4.23 (overlapping m, 2H); 4.39 (dd, ÍH); 5.06 (m, 1H); 6.04 (s, ÍH); 7.36 (dd, ÍH); 7.45 (t, ÍH); 7.51 (dd, ÍH); 9.00 (s, ÍH); 9.22 brs, 2H); (+ ÍH for HCl salt). MS (ESP): 476 (MH +) for C22H26F? 5? 4S 3- (4- (1- (2, 2-Dimethyl-1,3-dioxolan-4 (S) -ylcarbonyl) -1,2.5, 6-tetrahydropyrid-4-yl) -3-fluorophenyl) -5 (R) - (N- (-butoxycarbonyl) -1,2,5-thiadiazol-3-ylaminomethyl) oxazolidin-2-one Using the method described for appropriate intermediate of Example 17, apart from routine changes in the eluent used for chromatography, and starting from 3- (4- (1, 2, 5, 6-tetrahydropyrid-4-yl) -3-fluorophenyl hydrochloride ) -5 (R) - (N- (t-butoxycarbonyl) -1,2,5-thiadiazol-3-ylaminomethyl) oxazolidin-2-one (512 mg, 1 mM), gave the title product (597 mg, 99%). MR (400 MHz, DMSQ-d6) d: 1.35 (6H, s); 1.50 (s, 9H); 3.59-3.80 (m, 2H); 3.90 (m, 2H); 4.05-4.22 (m, 7H); 4.40 (dd, ÍH); 4.91 (m, ÍH); 5.06 (m, ÍH); 6..00 (s, 1H); 7.33 (dd, ÍH); 7.40 (t, 1H); 7.48 (dd, ÍH); 9.00 (s, ÍH). MS (ESP): 604 (MH *) for C28H34F? 507S Example 28: 3- (4- (1-Acetoxyacetyl-l, 2,5,6-tetrahydropyrid-4-yl) -3-fluorophenyl) -5 (S ) - (1,2,5-thiadiazol-3-ylaminomethyl) -oxazolidin-2-one Trifluoroacetic acid (2 ml) was added to a solution of 3- (4- (1-acetoxyacetyl-2, 5, 6) -tetrahydropyrid-4-yl) -3-fluorophenyl) -5 (R) - (N- (-butoxycarbonyl) -1,2,5-thiadiazol-3-ylaminomethyl) oxazolidin-2-one (467 mg, 0.812 mM) in dichloromethane (10 ml) and the solution was maintained for one hour. The solvent was evaporated and the residue redissolved in dichloromethane. The solution was washed with water, sodium bicarbonate solution, and brine and dried (sodium sulfate). The solvent was evaporated and the residue was purified on a Mega Bond Elut® silica column, eluting with dichloromethane and then 1.5% methanol in dichloromethane to give an oil which solidified in trituration with diethyl ether to give the title product (227 mg , 59%). NMR (400 MHz, DMSQ-d6) d: 2.14 (s, 3H); 2.51 (m overlapping DMSO, 2H); 3.64 (m, 1H); 3.72 (m, 3H); 3.90 (t, ÍH); 4.13 (m, 2H); 4.22 (t, ÍH); 4.89 (m, 2H); 5.00 (m, 1H); 6.10 (brs, ÍH); 7.37 (m, ÍH); 7.43 (m, 1H); 7.58 (dd, ÍH); 7.79 (t, ÍH); 8.10 (s, 1H). MS (ESP): 476 (MH *) for C21H22FN505S 3- (4- (1-Acetoxyacetyl-1, 2,5,6-tetrahydropyridi-4-yl) -3-fluorophenyl) -5 (R) - (N - ((t-butoxycarbonyl) -1,2,5-thiadiazol-3-ylaminomethyl) oxazolidin-2-one intermediate was prepared as follows: Using the method described for the appropriate intermediate of Example 25, but starting from the hydrochloride of 3 - (4- (1, 2, 5, 6-tetrahydropyrid-4-yl) -3-fluorophenyl) -5 (R) - (N- (t-butoxycarbonyl) -1,2,5-thiadiazol-3-ylaminomethyl) Oxazolidin-2-one (512 mg, 1 mM, see Example 27), gave the title product (472 mg, 82%). MR (400 MHz, DMSQ-d6) d: 1.38 (s, 9H); 1.97 (s, 3H); 2.39 brs, 2H); 3.45 (t, ÍH); 3.53 (m, ÍH); 3.92-4.14 (m, 6H); 4.26 (dd, ÍH); 4.71 (d, 2H); 4.92 (m, ÍH); 5.88 (brs, ÍH); 7.20 (dd, ÍH); 7.28 (m, ÍH); 7.38 (dd, ÍH); 8.85 (s, ÍH). MS (ESP): 577 (MH *) for C26H3? FN507S Example 29: 3- (4- (1-Hydroxyacetyl-l, 2,5,6-tetrahydropyrid-4-yl) -3-fluorophenyl) -5 (S ) - (1,2,5-thiadiazol-3-ylaminomethyl) -oxazolidin-2-one Using the method described in Example 26 but starting from 3- (4- (1-acetoxyacetyl-2, 5, 6-tetrahydropyrid-4-yl) -3-fluorophenyl) -5 (S) - (1, 2, 5-thiadiazol-3-ylaminomethyl) oxazolidin-2-one (199 mg, 0.42 mM, see Example 28), gave the product of the title (112 mg, 62%). "" NMR (400 MHz, DMSO-d6) d: 2.58 (m overlapping DMSO, 2H); 3.60 (t, ÍH); 3.75 (m, 3H); 3.91 (dd, ÍH); 4.10-4.28 (overlapping m, 5H); 4.61 (dt, ÍH); 4.96 (m, ÍH); 6.09 (m, ÍH); 7.36 (dd, ÍH); 7.45 (t, ÍH); 7.56 (dd, ÍH); 7.79 (t, ÍH); 8.10 (s, ÍH). MS (ESP): 434 (MH *) for C? 9H20FN5O4S Example 30: 3- (4- (1- (2 (S), 3-Dihydroxypropanoyl) -1,2,5,6-tetrahydropyrid-4-yl) 3,5-di-luo-phenyl) -5 (S) - (1,2,5-thia-diazol-3-ylaminomethyl) oxazolidin-2-one Using the method described in Example 27, apart from the routine changes in the eluent used for chromatography, and starting from 3- (4- (1- (2, 2-dimethyl-1,3-dioxolan-4 (S) -ylcarbonyl) -1,2,5,6-tetrahydropyridyl- 4-yl) -3,5-difluorophenyl) -5 (R) -. { N-. { -butoxycarbonyl) -1,2,5-thiadia-zol-3-ylaminomethyl) oxazolidin-2-one (650 mg, 1.05 mM) gave the title compound (265. mg, 53%). NMR (DMSO-de) d: 2.29 (m, ÍH); 2.38 (m, ÍH); 3.47 (m, ÍH); 3.55 (dd, ÍH); 3.64 (t overlapping m, 4H); 3.81 (dd, ÍH); 4.07 (m, ÍH); 4.16 (t, ÍH); 4.24 (m, ÍH); 4.36 (m, ÍH); 4.68 (br, ÍH); 4.92 (m, 2H); 5.85 (s, ÍH); 7.30 (d, 2H); 7.70 (t, 1H); 8.03 (s, 1H). MS (ESP): 482 (CH *) for C20H2? F2N5? 5S The 3- (4- (1- (2, 2-Dimethyl-l, 3-dioxolan-4 (S) -ylcarbonyl) -1.2, 5,6-tetrahydropyrid-4-yl) -3,5-difluorophenyl) -5 (R) - (N- (t-butoxycarbonyl) -1,2,5-thiadiazol-3-ylaminomethyl) oxazolidin-2-one intermediary was prepared as follows: Using the method described for the appropriate intermediate of Example 17, apart from routine changes in the eluent used for chromatography, and starting from 3- (4- (1, 2, 5, 6 hydrochloride -tetrahydropyrid-4-yl) -3,5-difluorophenyl) -5 (R) - (N- (t-butoxycarbonyl) -1,2,5-thiadiazol-3-ylaminomethyl) oxazolidin-2-one (800 mg, 1.51 mM, see Example 25), gave the title product (669 mg, 71%). MR (DMSO-de) d: 1.29 (s, 3H); 1.32 (s, 3H); 1.52 (s, 9H); 2.30 (m, ÍH); 2.40 (m, ÍH], 3.68 (m, 2H), 3.90 (dd, ÍH), 4.04-4.28 (m, 4H), 4.37 (m, ÍH), 4.90 (m, ÍH), 5.06 (m, ÍH); 5.72 (m, 2H); 5.88 (m, HH); 7.31 (d, 2H); 8.96 (s, HH) MS (ESP): 622 (MH *) for C28H33F2? 507S Example 31: 3- (4 - (1- (2 (S), 3-Dihydroxypropanoyl) -1,2,5,6-tetrahydropyrid-4-yl) -3,5-difluorophenyl) -5 (S) - (1,3,4-thiadiazole -2-ilaminomethyl) oxazolidin-2-one Using the method described in Example 27, apart from routine changes in the eluent used for chromatography, and starting from 3- (4- (1- (2, 2- dimethyl-1,3-dioxolan-4 (S) -ylcarbonyl) -1,2,5,6-tetrahydropyrid-4-yl), -3,5-difluorophenyl) -5 (R) - (N- (t- butoxycarbonyl) -1,3,4-thiadia-zol-2-ylaminomethyl) oxazolídin-2-one (190 mg, 0.30 mM) gave the title compound (75 mg, 51%).? MR (400 MHz, DMS0- d6) d: 2.33 (m, HH), 2.41 (m, 1H), 348 (m, HH), 3.55 (m, lH), 3.72 (overlapping m, 4H), 3.83 (dd, 1H), 4.12 (m , HH), 4.09 (t, 1H), 427 (m, HH), 437 (m, 1H), 4.69 (m, HH); 97 (m, 2H); 5.87 (s, 1H); 7.34 (d, 2H); 8.11 (t, 1H); 8.67 (s, ÍH). MS (ESP): 482 (MH +) for C2oH2? F2? 505S Intermediates for this compound were prepared as follows: 3- (4- (1-Benzyl-l, 2,5,6-tetrahydropyrid-4-yl) - 3, 5-difluorophene-nil) -5 (R) - (N- (fc-butoxycarbonyl) -1,3,4-thiadiazole-2-ylaminometry) oxazolidin-2-one Using the method described for the appropriate intermediate of Example 25, apart from the routine changes in the eluent used for chromatography, and starting from 3- (4- (1-benzyl-l, 2,5,6-tetrahydropyrid-4-yl) -3,5 -difluorophe-nyl) -5 (R) -hydroxymethyloxazolidin-2-one (3 g, 7.5 mM) and 2-t-butyloxycarbonlamino-1,3,4-thiazole (1.96 g, 9.75 mM) gave the title compound ( 1.58 g, 36%). MR (DMS0-d6) d: 1.50 (s, 9H); 2.31 (brs, 2H); 2.61 (t, 2H); 3.04 (m, 2H); 3.58 (s, 2H); 3.91 (dd, ÍH); 4.22 (t, ÍH); 4.32 (dd, ÍH); 4.49 (dd, ÍH); 5.09 (m, ÍH); 5.79 (brs, ÍH); 7.23-7.37 (overlapping m, 7H); 9.23 (s, ÍH). MS (ESP): 584 (MH *) for C29H3? F2N504S 2- -Butyloxycarbonylamino-1,3-thiadiazole 2-Amino-1,3,4-thiadiazole (5 g, 49.4 mM) was dissolved in dry pyridine (100 ml), and 4-dimethylaminopyridine (100 mg) and di-t-butyl dicarbonate (21.6 g, 98.9 mM) were added. The mixture was stirred at room temperature for 36 hours, then evaporated to dryness, finally rendered azeotroped with toluene. The residual oil, a mixture of mono- and di- (t-butoxycarbonyl) compounds was dissolved in methanol (100 ml), treated with aqueous sodium hydroxide (2 M, 25 ml, 50 mM) and stirred at room temperature for 2 hours. The mixture was acidified by the addition of citric acid (10% w / v, 80 ml), added in water (500 ml), and methanol was removed by evaporation. The resulting precipitate was filtered to give the title product as an off white solid (6.69 g, 67%). NMR (DMSO-de) d: 1.57 (s, 9H); 8.87 (s, ÍH); 10.67 (brSs, ÍH). MS (ESP): 202 (MH *) for C7HuN302S 3- (4- (2, 5, 6-Tetrahydropyrid-4-yl) -3,5-difluorophenyl) -5 (R) - (N- (t -butoxycarbonyl) -1, 3,4-thiadiazol-2-ylaminomethyl) oxazolidin-2-one Using the method described by the appropriate intermediate of Example 25, apart from routine changes in the eluent used for chromatography, and starting from 3- (4- ( 1-benzyl-l, 2, 5, 6-tetrahydropyrid-4-yl) -3,5-difluorophenyl) -5 (R) - (N- (t-butoxycarbonyl) -1,3,4-thiadiazole-2- ilaminomethyl) oxazolidin-2-one (1.54 g, 2.64 M), gave the title compound (845 mg, 60%). ? MR (DMSO-de) d: 1.50 (s, 9H); 2.53 (m, 2H); 3.25 (na overlapped by H20, 2H); 3.73 (s, 2H); 3.94 (t, ÍH); 4.32 (dd, ÍH); 4.49 (dd, ÍH); 5.10 (m, ÍH); 5.89 (s, ÍH); 7.35 (d, 2H); 9.21 (s, ÍH); 9.32 (brs, 2H); (+ ÍH for HCl salt). MS (ESP): 494 (MH +) for C22H25F2? 5? 4S 3- (4- (1- (2, 2-Dimethyl-1,3-dioxolan-4 (S) -ylcarbonyl) -1,2.5, 6-tetrahydropyrid-4-yl) -3,5-difluorophenyl) -5 (R) - (A7- (t-butoxycarbonyl) -1, 3, 4-thiadiazol-2-ylaminomethyl) oxazolidin-2-one Using the method described by the appropriate intermediate of Example 17, but starting from the hydrochloride of 3- (4- (1, 2, 5, 6-tetrahydropyrid-4-yl) -3,5-difluorophenyl) -5 (R) - ( ? - (t-butoxycarbonyl) -1,4,4-thiadiazol-2-ylaminomethyl) oxazolidin-2-one (400 mg, 0.755 mM) gave the title compound as an oil (205 mg, 44%). MS (ESP): 622 (MH *) for C28H33F2? 507S. Example 32: 3- (4- (1-Acetoacetyl-l, 2,5,6-tetrahydropyrid-4-yl) -3,5-di luoro enyl) -5 (S) - (1,3,4-thiadiazole -2-ilaminomethyl) -oxazolidin-2-one Using the method of Example 28, apart from the routine changes in the eluent used for chromatography, and starting from 3- (4- (1-acetoxyacetyl-2, 5,6-tetrahydropyrid-4-yl) -3,5-difluorophenyl) -5 (R) - (N- (t-butoxycarbonyl) -1,4,4-thiadiazol-2-ylaminomethyl) oxazolidin-2-one ( 120 mg, 0.20 mM) gave the title product (21 mg, 21%). MR (DMSO-d6) d: 2.10 (s, 3H); 2.34 (brs, ÍH); 2.43 (brs, ÍH); 3.60 (t, ÍH); 3.67 (dd, ÍH); 3.73 (dd, 2H); 3.85 (dd, 1H); 4.10 (m, 2H); 4.21 (t, ÍH); 4.85 (d, 2H); 4.98 MS (ESP): 494 (MH *) for C2? H2? F2? 505S 3- (4- (1-Acetoxyacetyl-l, 2,5,6-tetrahydropyrid-4-yl) -3,5-difluorophenyl) ) -5 (R) - (N- (-butoxycarbonyl) -1, 3, -thiadiazol-2-ylaminomethyl) oxazolidin-2-one intermediate was prepared as follows: Using the method described by the appropriate intermediate of Example 25, but starting from the hydrochloride of 3- (4- (1, 2, 5, 6-tetrahydropyrid-4-yl) -3-fluorophenyl) -5 (R) - (N- (t-butoxycarbonyl) -1,3, 4-thiadiazol-2-ylaminomethyl) oxazolidin-2-one (400 mg, 0.755 mM, see Example 31), gave the title product (135 mg, 30%). MS (ESP): 594 (MH *) for C 26 H 29 F 2? 507S Example 33: 5 (S) -Isoxazol-3-ylaminomethyl-3- (3,5-difluoro-4- (1-acetoxyacetyl-2,5, 6-tetrahydropyrid-4-yl) phenyl) oxazo-lidin-2-one. Reference Example 11 (3.21 g, 5.57 mmol) was dissolved in a solution of trifluoroacetic acid (10 ml) and dichloromethane (10 ml) by stirring at room temperature. room temperature for 10 minutes. The solvents were removed by rotary evaporation and the residue was azeotroped with toluene (2x), triturated and washed with diethyl ether, and dried to give the title compound as a creamy amorphous solid (2.65 g, 100%). NMR (300Mz, DMSOd6) d / ppm: 2.08 (s, 3H), 2.31 (m, ÍH), 2.42 (m, 1H), 3.44 (t, 2H, partially obscured), 3.57 (t, ÍH, partially obscured), 3.65 (t, ÍH, partially obscured), 3.82 (dd, 1H), 4.13 (m, 3H), 4.81 (s, ÍH), 4.85 (s, ÍH), 4.90 (m, 1H), 5.89 (m, 1H), 6.00 (d, ÍH), 6.55 (t, ÍH), 7.35 (m, 2H), 8.41 (d, ÍH). The starting material was prepared as follows: Reference Example 8: 3- (tert-butyloxycarbonylamino) -isoxazole To a stirred solution of 3-aminoisoxazole (5.00 g, 59. 5 mmole) and 4- (dimethylamino) pyridine (500 mg) in pyridine (100 ml) was added in portions of di-tert-butyl dicarbonate (25.97 g, 119 mmol) and stirred for 18 hours. The solvent was removed by rotary evaporation giving an oil which was dissolved in methanol (100 ml) and treated with a solution of NaOH (2.5 M, 24 ml, 60 mmol) was stirred for 2 hours, acidified with citric acid solution (10% w / v, 80 ml), and added in water (500 ml), giving the title compound as a light brown solid after filtration and drying. (8.89 g, 81%). NMR (300Mz, DMSOd6) d / ppm: 1.46 (s, 9H), 6.72 (d, ÍH), 8.71 (d, ÍH), 10.35 (s, broad, ÍH). MS + (M + H) = 129 (butylene loss). Reference Example 9A: 3, 5-Difluoro-4- (l-benzyl-4-hydroxy-hexahydropyrid-4-yl) aniline. NBuLi (1.32 M in hexanes, 350 ml, 0.462 mole) was added dropwise during 20 minutes to a solution of N, N- (1,2-bis (dimethylsilyl) ethane) -3,5-difluoroaniline (108.4 g, 0.40 mol, J. Org. Chem., 60, 5255-5261 (1995) in 800 ml of THF dry at -70 ° C under argon After stirring for an additional 4 hours at -70 ° C, N-benzyl-4-piperidone (87.8 g, 0.46 moles) in 270 ml of dry THF was added dropwise over 40 minutes at the same temperature and the reaction was allowed to stir at room temperature overnight The solvent was removed in vacuo and the resulting product was treated with ice and concentrated HCl and recovered in ether.The aqueous acidic phase was then treated with 40% NaOH with cooling, it was recovered in ether (and worked up by washing with water, with brine and drying with an anhydrous drying agent such as magnesium sulfate or sodium sulfate before evaporation - this processing method refers to how it was elaborated in the usual manner below) to give 144.7 g of a sludge. TLC analysis using 10% MeOH / dichloromethane on silica indicated that the desired alcohol appears as about 90% of the product, and the unpurified product was used without further purification. MS: ESP + (M + H) = 319. Reference Example 9B: 3, 5-Difluoro-4- (1-benzyl-l, 2,5,6-tetrahydropyrid-4-yl) aniline The unpurified product of Example of Reference 9A (144.7 g) was suspended in 400 ml of concentrated HCl and heated to reflux with stirring for 18 hours. The TLC showed all the starting material that had reacted, and after cooling on ice and the reaction mixture was recovered to pH 11 with concentrated NH3 (aqueous) and was recovered three times with dichloromethane. The usual work-up gave 119.5 g of a viscous oil. TLC indicated a purity of about 80% and the unpurified product was used without further purification. MS: ESP + (M + H) = 301. Reference Example 9C: N-Benzyloxycarbonyl-3,5-difluoro-4- (1-benzyl, 2,5,6-tetrahydropyrid-4-yl) aniline The aniline Without purification from Reference Example 9B (3.2 g, 10.7 mmol) in 10 ml of acetone was added in one portion to a stirred solution of sodium dihydrogen phosphate (3.0 g) in 30 ml of water. The resulting mixture was cooled to 5-10 ° C and a solution of benzylchloroformate (2.18 g, 1.8 ml, 12.8 mmol) in 10 ml of acetone was added by go. The mixture was stirred for an additional hour at an ice bath temperature and then at room temperature for 2 hours. The mixture was diluted with 80 ml of water, basified with concentrated NH3 (aqueous) and recovered in EtOAc. The usual workup gave a viscous oil which was purified by flash chromatography (silica Merck 9385, EtOAc / isohexane - (3: 7 eluent) and triturated with isohexane to give a solid (1.53 g., 33%). MS: ESP + (M + H) = 434. Reference Example 9D: 5 (R) -Hydroxymethyl-3- (4- (1-benzyl-1,2,5,6-tetrahydropyrid-4-yl) -3, 5-difluorophenyl) oxazolidin-2-one The benzylurethane from Reference Example 9C (5.54 g, 12.76 mmoles) in 50 ml of dry THF was cooled to -70 ° C under nitrogen and 8.80 ml of nBuLi 1.6M in hexanes ( 14.08 mmoles) was added dropwise at the same temperature. After 20 minutes at the same temperature, a solution of (R) -glycidyl butyrate (2.00 g, 13.88 mmol in 5 ml of THF) was added dropwise and the mixture was stirred for 30 minutes at -70 ° C and then stirred at room temperature overnight. After quenching with 100 ml of 10% ammonium chloride, the mixture was taken up in EtOAc and the usual work up to give an oily solid, which was purified by flash chromatography (silica Merck C60 5% eluent of MeOH / dichloromethane ) to give a crystalline solid (4.40 g, 86%) .. MS: ESP + (M + H) = 401. ^ -NMR (250MHz, DMSO-d6): d = 2.32 (m, 2H), 2.63 (t, 2H) ", 3.05 (m, 2H), 3.50-3.72 (m, 4H), 3.82 (dd, ÍH), 4.06 (t, ÍH), 4.73 (m, ÍH), 5.18 (t, ÍH), 5.78 ( m, HH) Reference Example 9: 5 (R) - (N-isoxazol-3-yl-N-terbutoxy-carboni1) aminomethyl) -3- (3, 5-difluoro-4- (l-benzyl-1 , 2, 5, 6-tetrahydropyrid-4-yl) phenyl) oxazolidin-2-one To a stirred solution of 5 (R) -hydroxymethyl-3- (3, 5-difluoro-4- (1-benzyl-1, 2,5,6-tetrahydropyrid-4-yl) phenyl) oxa-zolidin-2-one (Reference Example 9D; 6.01 g, 15 mmol), 3- (tert-butyloxycarbonylamino) -isoxazole (3.04 g, 16.5 mmol, Reference Example 8) and tri-n-butyl phosphine (4.55 g, 22.5 mmol, 5.55 mL) in dry THF (250 ml) under N 2, cooled to 0 ° C, was added in portions 1, 1 '- (azodicarbonyl) -di-piperidine (5.68 g, 22.5 mmol). The reaction was stirred at 0 ° C for 30 minutes, allowed to come to room temperature and stirred for an additional 4 hours, with the formation of a white precipitate. The mixture was filtered, concentrated by rotary evaporation to an oil which was purified by MPLC (Merck 9385 silica, 50% EtOAc / Hexane), concentrating the pure fractions to give the title compound as a white brittle foam (7.74 g. , 91%). NMR (300Mz, DMSO-d6) d / ppm: 2.33 (m, 2H), 3.41 (t, 2H), 3.53 (m, ÍH), 3.66 (m, 1H), 3.79 (dd, ÍH), 4.10 (m , 5H), 4.57 (m, 1H), 4.89 (m, HH), 5.83 (m, HH), 5.98 (d, 1H), 6.50 (t, HH), 7.33 (d, 2H), 8.38 (d, ÍH). MS: ES * (M + H) = 567. Reference Example 10: 5 (R) - (N-Isoxazol-3-yl-N-terbutoxycarbonyl) aminomethyl) -3- (3, 5-difluoro-4 hydrochloride - (1,2,5,6-Tetrahydropyrid-4-yl) phenyl) oxazolidin-2-one To a stirred solution, it was cooled to 0-4 ° C of Reference Example 9 (5.00 g, 8.82 mmol) in dichloromethane (50 ml), under N2, added N, N-diisopropylethylamine (462 μl, 2.65 mmol) and 1-chloroethyl chloroformate (1.64 g, 11.5 mmol, 1.24 ml) was allowed to stir for 10 minutes. The mixture was chromatographed by MPLC (Merck 9385 silica, 40% EtOAc / Hexane) and the pure fractions were concentrated by rotary evaporation and taken up in MeOH and heated to 60 ° C, with stirring for 30 minutes. Removal of the solvent and trituration with diethyl ether gave the title compound as a white amorphous powder (3.66 g, 81%). MS: ES + (M + H) = 477. Reference Example 11: 5 (R) - (N-isoxazol-3-yl-N-terbutoxy-carbonyl) aminomethyl) -3- (3, 5-difluoro-4- (l-acetoxyacetyl-1,2,5, 6-tetrahydropyrid-4-yl) phenyl) oxazolidin-2-one To a suspension of Reference Example 10, (3.00 g, 5.85 mmol) and sodium acid carbonate (2.46 g, 29.3 T rims) in acetone (100 ml) water (50 ml), stirred at 0 ° C, under N2 a solution of acetoxyacetyl chloride (879 mg, 6.44 mmol, 692 μl) in acetone (5 ml) was added dropwise. The reaction was stirred at 0 ° C for 30 minutes and at room temperature for an additional 90 minutes, then water was added and the mixture was taken up in EtOAc (2x) and the organic extracts were washed with water and saturated brine, dried (sodium sulfate). sodium) and concentrated by rotary evaporation to give the title compound as a white crunchy foam (3.29 g, 98%). NMR (300Mz, DMS0-d6) d / ppm: 1.48 (s, 9H), 2.08 (s, 3H), 2.30 (m, ÍH), 2.42 (m, 1H), 3.60 (dt, 2H), 3.86 (dd) , ÍH), 3.97 (dd, 1H), 4.10 (m, 2H), 4.22 (m, 2H), 4.82 (s, 1H), 4.87 (s, ÍH), 5.03 (m, ÍH), 5.89 (m, 1H), 6.89 (d, ÍH), 7.33 (m, 2H), 8.81 (d, 1H). Example 34: 5 (S) -Isoxazol-3-xlaminomethyl-3- (3,5-di-luoro-4- (1-hydroxyacetyl-l, 2,5,6-tetrahxdropirid-4-yl) phenyl) oxazolidin-2 -one Example 33 (2.0 g, 4.2 mmol) was suspended in saturated methanolic ammonia (25 ml), with stirring, heating at 50 ° C, for 10 minutes to completely dissolve the cooled solid at room temperature and allowed to stand for 18 hours. hours with the formation of some yellow precipitate which was further precipitated with diethyl ether and filtered to give the title compound as a yellow amorphous powder (1.82 g, 100%). NMR (300Mz, DMSO-d6) d / ppm: 2.32 (, 2H), 3.43 (t 2H), 3.53 (t 1H), 3.67 (m, ÍH), 3.79 (dd, ÍH), 4.10 (m, 5H) , 4.57 (m, ÍH), 4.88 (m, 1H), 5.85 (m, ÍH), 5.98 (d, ÍH), 6.50 (t, 1H), 7.30 (m, 2H), 8.3.7 (d, ÍH) ). MS: ES + (M + H) = 435. Example 35: 5 (S) -Isoxazol-3-ylaminomethyl-3- (3,5-di-luoro-4- (1- (2 (S), 3-dihydroxypropanoyl) -1,2,5,6-tetrahydropyrid-4-yl) phenyl) oxazolidin-2-one Reference Example 12 (420 mg, 0.69 mmol) was dissolved in trifluoroacetic acid (5 ml) and by stirring for 10 minutes. THF (5 ml) / water (5 ml) was then added and stirring was continued for 30 additional minutes. Water was then added and the reaction was taken up in ethyl acetate (2x) and the extracts were washed with water, saturated sodium hydrogen carbonate solution (2x) and saturated brine, then dried (sodium sulfate) and concentrated by rotary evaporation to give the title compound as a white solid (160 mg, 50%). NMR (300Mz, DMSO-d6) d / ppm: 2.23-2.42 (m, 2H), 3. 40-3.60 (m, 4H), 3.72 (dd, ÍH), 3.80 (dd, 2H), 4.13 (m, 3H), 4.37 (m, ÍH), 4.67 (m, ÍH), 4.89 (m, ÍH) , 4.96 (m, ÍH), . 85 (m, 1H), 5.98 (d, ÍH), 6.51 (t, ÍH), 7.32 (m, 2H), 8.37 (d, 1H). MS: ES + (M + H) = 465. The starting material was prepared as follows: Reference Example 12: 5 (R) - (N-isoxazol-3-yl-N-terbutoxy-carbonyl) aminomethyl) -3- (3, 5-difluoro-4- (1- (2,2-dimethyl-l, 3-dioxolan- (S) -ylcarbonyl) -1,2,5,6-tetrahydropyrid-4-yl) phenyl) oxazolidin- 2-one To a stirred solution of Reference Example 10, (650 mg, 1.27 mmol) and pyridine (514 μl, 6.35 mmol) in dichloromethane (25 ml), cooled to 0 ° C, under N2, added by dripping (S) - (+) - 2, 3-0-isopropylidene glycinyl chloride (EP 0 413401 A2) (418 mg, 2.54 moles). The reaction was stirred for 30 minutes at 0 ° C then 1 hour at room temperature and the organic phase was washed with water (10 ml), concentrated by rotary evaporation and the title compound was obtained by crystallization with methanol as a white powder (500 mg, 65%). NMR (300Mz, DMSO-d6) d / ppm: 1.30 (s, 3H), 1.32 (s, 3H), 1.48 (s, 9H), 2.31 (m, ÍH), 2.42 (m, 1H), 3.67 (t , ÍH), 3.75 (t, 1H) ', 3.87 (dd, ÍH), 3.96 (dd, 1H), 4.01-4.32 (m, 6H), 4.90 (m, 1H), 5.01 (m, ÍH), 5.90 (m, ÍH), 6.88 (d, ÍH), 7.35 (m, 2H), 8.82 (d, ÍH). MS: + (M + H) = 605. There are no Examples 36 or 37 Example 38: 5 (S) -Isoxazol-3-ylaminomethyl) -3- (3, 5-difluoro-4- (3,6-dihydro-) (2H) -pyran-4-yl) phenyl) oxazolidin-2-one To a stirred solution of Reference Example 13, (273 mg, 0.49 mmol) in AcOH (4.5 ml) / water (0.5 ml), under N2, zinc powder (160 g, 2.45 mmol) was added. The reaction was stirred for 16 hours, the mixture was filtered through celite, washing the filter pad with AcOH (0.5 ml). The solvent was removed from the filtrate by rotary evaporation and the gum obtained was dissolved in dichloromethane (20 ml) and washed with water (10 ml), saturated sodium hydrogen carbonate solution (10 ml) and brine (10 ml). ).

The organic layer was dried (sodium sulfate), evaporated and the title compound was obtained as a pale yellow solid (140 mg, 76%) until triturated with diethyl ether and dried. NMR (300Mz, DMSO-d6) d / ppm: d 2.30 (m, ÍH), 3.45 (m, 1H), 3.81 (, 3H), 4.18 (m, 3H), 4.90 (, ÍH), 5.91 (br s) , ÍH), 6.00 (d, ÍH), 6.53 (m, ÍH), 7.34 (m, 2H), 8.40 (d, 1H). The starting material was prepared as follows: Reference Example 13: 5 (R) - (N-isoxazol-3-yl-N-terbutoxy-carbonyl) aminomethyl) -3- (3, 5-difluoro-4- (3 , 6-dihydro- (2H) -pyran-4-yl) enyl) oxazolidin-2-one To a stirred solution of 3- (TROC-a ino) -isoxazole (Reference Example 1; 310 mg, 1.20 mmol), 5 (R) -hydroxymethyl-3- (3, 5-difluoro-4- (3,6-dihydro- (2H) -pyran-4-yl) -phenyl) oxazolidin-2-one (see WO97 / 30995 Example of Reference 14; 250 mg, 0.80 mmol) and tri-n-butyl phosphine (242 mg, 1.20 mmol) in dry THF (10 ml), under N2, cooled to 0 ° C, a solution of 1.1 '- (azodicarbonyl) -di-piperidine (303 mg, 1.20 mmol) in Dry THF (1.5 ml). The reaction was stirred at room temperature for 2 hours, the solvent was removed by evaporation. The residue was dissolved in dichloromethane, cooled for 30 minutes and filtered to remove the white precipitate, then chromatographed by MPLC. (Merck silica 9385, 30% EtOAc / Hexane), and the pure fractions were evaporated to give the title compound as clear glasses (386 mg, 65%). NMR (400Mz, DMSO-d6) d / ppm: d 2.27 (m, 2H), 3.78 (m, 2H), 3.89 (dd, 1H), 4.16 (m, 4H), 4.35 (dd, ÍH), 5.02 ( m, 3H), 5.87 (br s, ÍH), 6.85 (d, ÍH), 7.26 (m, 2H), 8.87 (d, ÍH). MS: ES + (M + H) = 552 (3x Cl isotope standard). Example 39: 5 (S) -Isoxazol-3-ylaminomethyl-3- (3-fluoro-4- (1- (2- (N-ethoxycarbonylmethyl) -carbamoyloxy) -acetyl-1, 2,5,6-tetra- hydropyrid-4-yl) phenyl) oxazolidin-2-one. In portions, 2-isocyanato-ethyl acetate (3x170 mg, 3.96 mmol) was added dropwise to a stirred suspension of Example 5, (500 mg, 1.2 mmol), triethylamine (334 μl, 2.40 mmol) and 4- (dimethylamino) pyridine (8 mg) in dioxane (20 ml) and the reaction was heated at 80 ° C for 64 hours. The solvent was removed by rotary evaporation and the title compound was isolated after MPLC (Merck silica 9385, 80-100%, EtOAc / Hexane) and trituration with diethyl ether as a white powder (410 mg, 63%). NMR (300Mz, DMSO-d6) d / ppm: 1.77 (t, 3H), 2.41 (m, 2H), 3.43 (t, 2H), 3.53 (m, ÍH), 3.62 (m, ÍH), 3.74 (d , 2H), 3.80 (dd, ÍH), 4.03-4.18 (m, 5H), 4.68-4.77 (m, 2H), 4.87 (m, 1H), 5.98 (m, 2H), 6.50 (t, ÍH), 7.27-7.52 (m, 3H), 7.73 (t, 1H), 8.37 (d, 1H). MS: ES + (M + H) = 546. Example 40: 5 (S) -Isoxazol-3-ylaminomethyl-3- (3-fluoro-4- (1- (2- (N-carboxymethyl) -carbamoyloxy) -acetyl -1, 2,5,6-tetrahydro-pyrid-4-yl) phenyl) oxazolidin-2-one To a stirred solution of Example 39 (500 mg, 0.9 mmol) in methanol / water (1: 1, 25 ml) a solution of lithium hydroxide monohydrate (43.5 mg, 1.0 mmol) in water (2.5 ml) was added. The reaction was stirred at room temperature for 20 minutes, added to water (100 ml) and stirred with Dowex 50Wx8 (H) resin (4 ml) for 5 minutes. The resin was removed by filtration and the solvent was removed by rotary evaporation to give a gum which was dissolved in 10% methanol / dichloromethane and the title compound was obtained as a pale yellow crunchy foam (433 mg, 93%) by evaporation and drying. NMR (300Mz, DMSO-d6) d / ppm: 2.42 (m, 2H), 3.10 (t, 1H), 3.33-3.67 (m, 6H), 3.81 (dd, ÍH), 3.98-4.20 (m, 3H) , 4.72 (m, 2H), 4.86 (m, HH), 5.99 (m, 2H), 6.52 (t, HH), 7.15-7.53 (m, 4H), 8.37 (d, HH.) MS: ES- ( MH) - = 516. Example 41: 5 (S) -Tiazol-2-ylaminomethyl) -3- (3-fluoro-4- (3,6-dihydro- (2H) -pyran-4-yl) phenyl) oxazolidin -2-one To a stirred solution of 2-aminothiazole (228 mg, 2.22 mmol) in dry THF (5 ml), cooled to -78 ° C under argon, n-BuLi (1.33 M, 1.67 ml, 2.22 mmoles), followed after 30 minutes by 5 (R) -methylsulfonyloxymethyl-3- (3-fluoro-4- (3,6-dihydro- (2H) -pyran-4-yl) phenyl) oxazolidin-2-one (prepared using standard chemistry of compound 5 (R) -hydroxymethyl by analogy with compound 3, 5-difluoro; see WO97 / 30995; 542 mg, 1.46 moles) was suspended in dry THF (25 ml). The reaction was stirred for 18 hours at the mixture with chloroform (3 x 10 ml). The extracts were dried (magnesium sulfate at room temperature, then heated at 50 ° C for 2 hours.) The reaction was quenched with ammonium chloride solution (10% w / v, 30 ml) and acidified to pH 3.0 with aqueous HCl, extracting) concentrated by rotary evaporation, chromatography by MPLC (silica Merck 9385, 3% eluent of methanol / dichloromethane) and the combined pure fractions to give the crude product (68 mg) which was recrystallized from Ethanol was washed with diethyl ether and dried to give the title compound as a yellow powder (40 mg, 7.3%). NMR (300Mz, DMSO-d6) d / ppm: 2.41 (m, 2H), 3.25 (m, 2H), 3.65 (dd, ÍH), 3.80 (t, ÍH), 3.91 (dd, ÍH), 3.99 (dd, ÍH), 4.18 (m, 3H), 4.63 (m, ÍH), 6.06 (m, ÍH) ), 7.23 (dd, ÍH), 7.38 (m, 2H), 7.44 (d, ÍH), 7.59 (dd, ÍH). MS: ES + (M + H) = 376. Example 42: 5 (S) - (N-Methyl) imidazol-2-ylaminomethyl) -3 (3-fluoro-4- (3,6-dihydro- (2H) - piran-4-yl) phenyl) oxazolidin-2-one To a stirred solution of l-methyl-2-aminoimidazole (401 mg, 3.0 mmol) in dry THF (10 ml) was cooled to -78 ° C, under argon, n-BuLi (1.33 M, 4.5 ml, "6.0 mmol) was added slowly, followed after 1 hour by 5 ml. (R) -methylsulfonyloxymethyl-3- (3-fluoro-4- (3,6-dihydro- (2H) -pyran-4-yl) phenyl) oxazolidin-2-one (see Example 41; 542 mg, 1.46 moles) it was suspended in dry THF (20 ml) The reaction was allowed to come to room temperature and then brought to reflux for 18 hours.The reaction was quenched with ammonium chloride solution (10% w / v 30 ml), extracting mixture with chloroform (5 x 20 ml) The extracts were dried (sodium sulfate), concentrated by rotary evaporation, MPLC chromatography (Merck 9385 silica, 3% methanol / dichloromethane eluent) and the pure fractions were combined. to give the title compound (25 mg, 4.6%). NMR (300Mz, DMSO-d6) d / ppm: 2.40 (m, 2H), 3.36-3.56 (m, 5H), 3.82 (m, 3H), 4.06 -4.32 (m, 4H), 5.06 (m, ÍH), 6.05 (m, ÍH), 6.82 (s, 1H), 7.11 (s, ÍH) ), 7.32 (m, 2H), 7.55 (d, ÍH). MS: ES + (M + H) = 373. Example 43: 5 (S) ~ Oxazol-2-ylaminomethyl-3- (3-fluoro-4- (3,6-dihydro- (2H) -pyran-4-yl ) phenyl) oxazolidin-2-one To a stirred partial solution of 2-aminooxazole (169 mg, 2.0 mmol) in dry THF (10 ml), cooled to -78 ° C, under argon, n-BuLi was slowly added ( 1.33 M, 1.5 ml, 2.0 mmol) followed after 1 hour by 5 (R) -methylsulfonyloxymethyl-3- (3-fluoro-4- (3,6-dihydro- (2H) -pyran-4-yl) phenyl) oxazolidin-2-one (see Example 41; 371 mg, 1.0 moles) was suspended in dry THF (20 ml). The reaction was allowed to come to room temperature and then brought to reflux for 24 hours. The reaction was quenched with ammonium chloride solution (10% w / v, 30 ml), the mixture was taken up in chloroform (3 x 50 ml). The extracts were dried (magnesium sulfate), concentrated by rotary evaporation, taken to MPLC chromatography (Merck 9385 silica, 3-10 gradient eluent of methanol / dichloromethane) and the combined pure fractions were concentrated and triturated with diethyl ether to give the title compound (25 mg, 4.6%). - NMR (300Mz, DMSO-d6) d / ppm: 2.31 (m, 2H), 3.35 (m, 2H, darkened), 3.64 (dd, ÍH), 3.84 (t, 2H), 3.90 (m, ÍH), 4.15 (, ÍH), 4.24 (m, 2H), 4.46 (m, ÍH), 5.97 (m, ÍH), 6.90 (m, ÍH), 7.19 (m, 2H, partially obscured), 7.37 (dd, 1H), 7.44 (dd, ÍH). MS: ES + (M + H) = '360. Example 44: 5- (S) - (Isoxazol-3-ylaminometryl) -3- (4- (1,2,5,6-tetrahydropyrid-4-yl) phenyl) oxazolidin-2-one trifluoroacetate The material of Starting from Reference Example 14, (2.65 g, 4.9 mM) was dissolved in TFA (10 ml), giving a bright yellow color and evolution of gas. This was briefly heated to reflux. The TFA was evaporated and the residue was taken up in ethyl acetate. The title compound was crystallized (1.56 g, 70%). . NMR (300Mz, DMSO-d6): d 2.69 (s, 2H), 3.31 (d, 2H), 3.44 (t, 2H), 3.78 (s, 2H), 3.84 (d of d; ÍH), 4.18 (t , ÍH), 4.88 (m, 1H), 6.00 (s, 1H), 6.20 (s, ÍH), 6.59 (t, ÍH), 7.53 (AB, 4H), 8.40 (s, ÍH), 8.89 (s, 2H). MS: ES + (M + H) = 312. The starting material was prepared as follows: Reference Example 14: 5 (R) - (N-isoxazol-3-yl-N-terbutoxy-carbonyl) aminomethyl) -3- (4- (1-tert-butoxycarbonyl) -1,2,5,6-tetrahydropyrid-4-yl) phenyl) oxazolidin-2-one To a stirred solution of 5 (R) -hydroxymethyl-3- (1-tert-butoxycarbonyl-1) , 2, 5, 6-tetrahydropyrid-4-yl) phenyl) oxazolidin-2-one (prepared by analogy to the compound 3,5-difluoro - see WO97 / 30995 Reference Example 11; 2.24 g, 6.0 mM) and N- Boc-isoxazole (1.66 g, 9.0 mM) in dry THF (30 ml) under N2, added tri-N-butylphosphine (1.82 g, 9.0 mM) followed by portionwise addition of ADDP (2.27 g, 9.0 mM). The reaction mixture was stirred for 18 hours at room temperature. This was evaporated and taken to MPLC chromatography (35% ethyl acetate / isohexane, Merck silica 9385). The title compound was crystallized in trituration with isohexane (2.75 g.; 85%). NMR (300Mz, DMSO-d6): d 1.35 (s, 9H), 1.43 (s, 9H), 2.4 partially obscured by DMSO), 3.48 (t, ÍH), 3.78 (4 line, 1H), 3.92 (m, 3H), 4.18 (m, 2H), 4.92 (m, ÍH), 6.18 (s, 1H), 6.80 (s, ÍH), 7.43 (AB, 4H), 8.75 (s, ÍH). MS: ES + (M + H) = 485 (-butylene), 429 (-2x butylene). Example 45: 5 (S) - (Isoxazol-3-ylaminomethyl) -3- (4- (1-acetoxyacetyl-1, 2,5,6-tetrahydropyrid-4-yl) phenyl) oxazolidin-2-one To one solution stirred from the starting material of Example 44 (590 mg, 1.3 mM) in acetone (20 ml) / water (10 ml), NaHCO3 (1.09 g, 13 mM) was added and the mixture was cooled to 0-4 ° C. Acetoxyacetyl chloride (350 mg, 2.6 mM) was added slowly and the reaction mixture was stirred at 0-5 ° C for 20 minutes, then allowed to warm to room temperature. The reaction mixture was diluted with water and recovered in ethyl acetate. The organic phase was washed with saturated NaCl, dried over anhydrous Na 2 SO 4 and evaporated. The title compound was crystallized from trituration with ether (570 mg, 100%). NMR (300Mz, DMSO-d6): d 2.08 (s, 3H), 2.55 (partially obscured by DMSO), 3.45 (t, 2H), 3.58 (t,MR. 1H), 3.67 (t, ÍH), 3.84 (d of d, ÍH), 4.10 (s, 2H), 4.18 (t, ÍH), 4.85 (m, 3H), 6.00 (s, ÍH), 6.15 (broad d, ÍH), 6.53 (t, 1H), 7.50 (m, 4H), 8.38 (s, ÍH). Example 46: 5 (S) - (Isoxazol-3-ylaminomethyl) -3- (4- (1-hydroxyacetyl-l, 2,5,6-tetrahydropyrid-4-yl) enyl) oxazolidin-2-one A partial solution of the starting material of Example 45 (500 mg, 1.1 mM) in saturated NH3 / methanol (15 ml) was heated to give a clear solution after 5 minutes. The reaction mixture was stirred for 18 hours at room temperature. The solvent was evaporated to a small volume and ether added to give the title compound as a crystalline solid (394 mg, 90%). NMR (300Mz, DMSO-d6): d 2.5 (obscured by DMSO), 3.38 (t, 2H), 3.48 (t, 1H), 3.62 (t, ÍH), 3.73 (d of d, ÍH), 4.6 (m , 5H), 4.52 (m, ÍH), 4.79 (m, ÍH), 5.94 (s, ÍH), 6.09 (d, 1H), 6.50 (t, ÍH), 7.44 (AB, 4H), 8.32 (s, ÍH). MS: ES + (M + H) = 399. Example 47: 5 (S) - (Isoxazol-3-ylaminomethyl) -3- (4- (1- (2, 2-dimethyl-1,3-dioxolan- 4 (S) -ylcarbonyl) -1,2,5,6-tetrahydropyrid-4-yl) phenyl) oxazolidin-2-one 1 A stirred partial solution of the starting material of Example 44 (300 mg, 0.66 mM) and NaHCO 3 (178 mg, 3.3 mM) in acetone (8 ml) / water (4 ml), cooled to 0-4 ° C. A solution of (S) - (+) -2, 3, 0-isopropylidene glycineyl chloride (217 mg, 1.32 mM) in acetone (1 ml) was added slowly and the reaction mixture was then allowed to warm to room temperature. An addition in addition to acyl chloride (139 mg, 0. 66 M) 'was required to complete the reaction. The reaction mixture was diluted with water and recovered in ethyl acetate. The organic phase was washed with saturated NaCl, dried over anhydrous Na 2 SO 4, and evaporated. The title compound was crystallized from trituration with ether (258 mg, 84%). NMR (300Mz, DMSO-d6): d 1.32 (m, 6H), 2.S5 (partially obscured by DMSO), 3.44 (t, 2H), 3.68 (m, 2H), 3.82 (d of d, ÍH), 4.15 (m, 5H), 4.88 (m, 2H), 6.01 (s, 2H), 6.16 (s, 1H), 6.55 (t, ÍH), 7.50 (AB, 4H), 8.40 (s, ÍH). MS: ES + (M + H) = 429. Example 48: 5 (S) - (Isoxazol-3-ylaminomethyl) -3- (4- (1- (2 (S), 3-dihydroxypropanoyl) -1,2, 5,6-tetrahydropyrid-4-yl) phenyl) oxazo-lidin-2-one A solution of the starting material of Example 47, (220 mg, 0.47 mM) in THF (6 ml) / IN aqueous HCl (2 ml) it was stirred for 3 days at room temperature. The solution was partially evaporated to give a gum and the aqueous solution was decanted. The title compound was crystallized from trituration of the gum with ethanol / ether (141 mg, 70%). NMR (300Mz, DMSO-d6): d 2.5 (obscured by DMSO), 3.45 (m, 4H), 3.80 (m, 3H), 4.25 (m, 4H), 4.73 (broad s, ÍH), 4.89 (m, 2H), 5.98 (s, ÍH), 6.15 (s, ÍH), 6.55 (s, ÍH), 7.48 (m, 4H), 8.36 (s, ÍH). MS: ES + (M + H) = 429. Example 49: 5 (S) - (1, 2, 4-Oxadiazol-3-yl-aminomethyl) -3- (3, 5-difluoro-4- (1- ( 2 (S), 3-dihydroxypropanoyl) -1,2,5,6-tetrahydro-pyrid-4-yl) phenyl) oxazolidin-2-one To a stirred solution of the Reference Example , (278 mg, 0.46 mmol) in dichloromethane (4 ml) was added trifluoroacetic acid (4 ml) and the reaction was allowed to stir at room temperature for 0.5 hour. Water (0.8 ml) was then added and the reaction was stirred for an additional 2 hours. The solvent was removed under reduced pressure and the resulting residue was taken up in methanol (15 ml). The solution was made slightly basic (pH 9) by the addition of concentrated ammonia solution. The solvent was removed by evaporation and the reaction was purified by Bond Elute silica (5% methanol in dichloromethane). Again the solvent was removed to yield the title compound as a white foam (152 mg, 71%). NMR (300Mz, DMSO-d6): d = 2.27-2.43 (m, 2H), 3.40-3.60 (, 4H), 3.73 (d, 2H), 3.83 (dd, ÍH), 4.05-4.41 (m, 4H) , 4.72 (m, 1H), 4.90 (m, ÍH), 5.02 (m, ÍH), 5.88 (broad s, ÍH), 7.26-7.39 (m, 3H), 9.04 (s, ÍH). MS: ESP + (M + H) * = 466. The starting material was prepared as follows: Reference Example 15: 5 (R) - (N-1), 2,4-oxadiazol-3-yl-N-terbutoxycarbonyl) -aminomethyl) -3- (3, 5-difluoro-4- (1- (2, 2-dimethyl-1, 3-dioxolan-4 (S ) -carbonyl) -1,2,5,6-tetrahydropy-rid-4-yl) phenyl) oxazolidin-2-one To a stirred solution of the appropriate intermediate of Example 20 (600 mg, 1.37 mmol) in anhydrous THF (30 mg). ml) under a nitrogen atmosphere was added 3-t-butloxycarbonylamino-1,2,4-oxadiazole (304 mg, 1.64 mmole) and tri-n-butylphosphine (510 μL 2.05 mmole). The mixture was cooled to 0 ° C and 1.1 '- (azodicarbonyl) -di-piperidine (518 mg, 2.05 mmol) was added in portions. The reaction was allowed to warm to room temperature and was stirred for 18 hours. The THF was removed under reduced pressure and the resulting residue was taken up in dichloromethane (15 ml) and cooled to 0 ° C. A white solid precipitated and the solution was filtered and purified by MPLC (Merck silica 9385, 40-60% ethyl acetate in iso-hexane). The solvent was removed under reduced pressure to give a clear colorless oil, which was triturated with ether to yield the title compound as a fine white powder (291 mg, 35%). ^ - R (300MHz, DMSO-d6): d = 1.31 (d, 6H), 1.47 (s, 9H), 2.27-2.48 (m, 2H), 3.61-4.28 (m, 10H), 4.87-5.02 (m , 2H), 5.89 (broad s, ÍH), 7.33 (d, 2H), 9.54 (s, ÍH). MS: ESP + (M + H) * = 606. Example 50: 5 (S) - (1, 2, 4-Oxadiazol-3-yl-aminomethyl) -3- (3, 5-difluoro-4- (1- hydroxyacetyl-l, 2,5,6-tetrahydropyrid-4-yl) -phenyl) oxazolxdin-2-one To a stirred solution of Reference Example 19 (240 mg, 0.55 mmol) in dichloromethane (4 ml) was added trifluoroacetic acid (4 ml) and the reaction was allowed to stir at room temperature for 1 hour. The solvent was removed under reduced pressure and the resulting residue was taken up in methanol (15 ml). The solution became slightly basic (pH 9) by the addition of concentrated ammonia solution. The solvent was removed by evaporation and the reaction was purified by MPLC (Merck silica 9385, 5% methanol in dichloromethane).

The solvent was concentrated under reduced pressure and the product was precipitated in the remaining solvent. The product was filtered, washed with freshly cooled ice methanol and then triturated with ether to give the title compound as a white solid (135 mg, 69%). XH-NMR (300MHz, DMSO-d6): d = 2.25-2.44 (m, 2H), 3.42-3.59 (m, 3H), 3.69 (m, 1H), 3.83 (dd, ÍH), 4.0-4.21 (m , 5H), 4.55-4.70 (m, HH), 4.89 (m, HH), 5.81-5.91 (m, HH), 7.29-7.40 (m, 3H), 9.05 (s, HH). MS: ESP + (M + H) * = 436. The starting material was prepared as follows: Reference Example 16: 5 (R) - (Nl, 2,4-oxadiazol-3-yl-N-terbutoxycarbonyl) amino- methyl) -3- (3, 5-difluoro-4- (1-benzyl-1,2,5,6-tetrahydropyrid-4-yl) phenyl) oxazolidin-2-one 5 (R) -hydroxymethyl- 3- (3,5-difluoro-4- (1-benzyl-l, 2,5,6-tetrahydropyrid-4-yl) phenyl) -oxazolidin-2-one (Reference Example 9D, 1.65 g, 4.13 mmol) , 3-t-butyloxycarbonylamino-1,4,4-oxadiazole (1.14 g, 6.19 mmol), tri-n-butylphosphine (1.52 mL, 6.19 mmol) and 1,1 '- (azodicarbonyl) -di-piperidine (1.56 g) , 6.19 mmole) in anhydrous THF (60 ml) using the general method of Reference Example 15. The reaction mixture was then purified by MPLC (Merck silica 9385, 60% ethyl acetate in isohexane) and the solvent was removed under reduced pressure to give the title compound as a white foam (1.56 g, 67%). ^ - MR (300MHz, DMSO-d6): d = 1.47 (s, 9H), 2.32 (broad s, 2H), 2.62 (t, 2H), 3.05 (broad s, 2H), 3.60 (s, 2H), 3.85 (dd, ÍH), 4.0 (m, ÍH), 4.14-4.28 (m, 2H), 4.97 (m, ÍH), 5.79 (broad s, ÍH), 7.21-7.38 (m, 7H), 9.53 (s) , ÍH). MS: ESP + (M + H) * = 568. Reference Example 17: 5 (R) - (Nl, 2,4-oxadiazol-3-yl-N-terbutoxycarbonyl) amino-methyl) -3- (3, 5 -Difluoro-4- (1, 2, 5, 6-tetrahydropyrid-4-yl) phenyl) oxazolidin-2-one To a stirred solution of Reference Example 16 (1.55 g, 2.73 mmol) and N, N-diisspropylethylamine ( 142 μL, 20.3 mmol) in dichloromethane (25 mL) under a nitrogen atmosphere at 0-4 ° C was added dropwise to 1- chloroethyl chloroformate (384 μL, 3.55 mmol). The reaction was allowed to stir for 30 minutes at 0 ° C and the dichloromethanes were removed under reduced pressure to produce a brown residue. Methanol (25 ml) was added and the resulting brown solution was heated at 6 ° C for 30 minutes in a water bath. The methanol was removed under reduced pressure to produce a brown / red residue which was purified by Bond Elut silica (25% methanol in dichloromethane). The solvent was removed under • reduced pressure to give the title compound as a white foam (726 mg, 52%). ^ -NMR (300MHz, DMSO-d6): d = 1.44 (s, 9H), 2.50 (2H, obscured by DMSO), 3.28 (t, 2H), 3.74 (broad s, 2H), 3.86 (dd, 1H) , 3.95-4.03 (m, ÍH), 4.15-4.25 (m, 2H), 4.98 (, 1H), 5.90 (broad, s, 1H), 7.37 (d, 2H), 9.28 (broad s, 2H), 9.55 (Yes H) .

S: ESP + (M + H) * = 478. Reference Example 18: 5 (R) - (Ni, 2,4-oxadiazol-3-yl-N-terbutoxycarbionyl) amino-methyl) -3- (3, 5-difluoro-4- (l-acetoxy) aceti 1-1 2 5 6-tetrahydropyrid- • 4-yl) phenyl) -oxazolidin-2-one To a stirred solution of Reference Example 17 (720 mg, 1.40 mmol) and NaHCO 3 (1.18 g, 14.0 mmol) in acetone (20 ml) / water (10 ml) at 0-4 ° C were added dropwise acetoxyacetyl chloride (301 μL, 2.80 mmol). The reaction was allowed to warm to room temperature and was stirred for 1 hour. The reaction was diluted with water and the product was taken up in ethyl acetate. The combined organic phases were washed with saturated NaCl, dried over MgSO4, and evaporated under reduced pressure. The resulting yellow oil was triturated with ether to give the title compound as an off-white solid (647 mg, 80%). XH-NMR (300MHz, DMSO-d6): d = 1.45 (s, 9H), 2.10 (s, 3H), 2.26-2.46 (m, 2H), 3.51-3.68 (m, 2H), 3.85 (dd, 1H) ), 3.95-4.01- (m, ÍH), 4.07-4.13 (m, 2H), 4.16-4.27 (m, 2H), 4.79-4.88"(m, 2H), 4.96 (m, ÍH), 5.86 (m , 1H), 7.33 (d, 2H), 9.53 (s, ÍH) MS: ESP + (M + H) * = 578. Reference Example 19: 5 (R) - (Nl, 2,4-oxadiazole-3) -yl-N-terbutoxycarbonyl) amino-methyl) -3- (3, 5-difluoro-4- (1-hydroxy-acetyl-1, 2,5,6-tetrahydropyrid-4-yl) phenyl) -oxazolidin- 2-one Reference Example 18 (640 mg, 1.11 mmol) was stirred under a nitrogen atmosphere in saturated methanolic ammonia solution (25 ml) with gentle heating to aid in the dissolution of the starting material. the reaction was allowed to stir at room temperature for 20 hours.The solvent was removed under reduced pressure and the resulting residue was purified by MPLC (silica Merck 9385, 5% methanol in dichloromethane) .The solvent was removed again to give the this of the title as a white foam (255 mg, 43%). ^ - MR (300MHz, DMSO-d6): d = 1.48 (s, 9H), 2.25-2.43 (m, 2H), 3.53 (m, ÍH), 3.69 (m, ÍH), 3.84 (dd, ÍH), 3.95-4.27 (m, 7H), 4.56-4.70 (m, HH), 4.97 (m, 1H), 5.84-5.92 (m, HH), 7.35 (d, 2H), 9.54 (s, HH). MS: ESP + (M + H) * = 536. Example 51: 5 (S) - (Isoxazol-3-yl-aminomethyl) -3- (4-morpholino-phenyl) -oxazolidin-2-one Example 1 was stirred. Reference 20, (400 mg, 0.90 mmol) in trifluoroacetic (5 ml) with heating to aid in the dissolution of the starting material. Once in solution, the reaction was allowed to stir at 60 ° C for 15 minutes. The trifluoroacetic acid was removed under reduced pressure and the residue was azeotroped with toluene. The residue was then taken up in dichloromethane and washed with saturated NaHCO 3, water, saturated NaCl, and finally dried over MgSO 4. The solvent was removed under reduced pressure and the resulting solid was triturated with ether to yield the title compound as an off-white solid (260 mg, 84%). ^? - NMR (300MHz, DMSO-d6): d = 3.06 (t, 4H), 3.42 (t, 2H), 3.70-3.83 (, 5H), 4.10 (t, ÍH), 4.81 (m, ÍH), 6.0 (d, ÍH), 6.55 (t, ÍH), 6.97 (d, 2H), 7.40 (d, 2H), 8.40 (d, ÍH). MS: ESP + (M + H) * = 345. The starting material was prepared as follows: Reference Example 20: 5 (R) - (N-isoxazoi-3-yl-N-terbutoxy-carbonyl) aminomethyl) -3 - (4-morpholinophenyl) oxazolidin-2-one 5 (R) -hydroxymethyl-3- (4-morpholinophenyl) oxazolidin-2-one (prepared by analogy to the 3-fluoro compound - see WO95 / 07271) was reacted; 0.50 g; 1.80 mmole), 3-t-butoxycarbonylamino-isoxazole (0.50 g, 2.70 mol), tri-n-butylphosphine (0.66 ml, 2.70 mmol), and 1.1 '- (azodicarbonyl) -di-piperidine (0.68 g, 2.70 mmoles) in anhydrous THF (30 ml) using the general method of Reference Example 15. The reaction was then purified by MPLC (Merck silica 9385, 70% ethyl acetate in iso-hexane) and the solvent was removed under pressure. reduced to give a solid which was triturated with ether to give the title compound as an off-white solid. XH-NMR (300MHz, DMSO-d6): d = 1.50 (s, 9H), 3.08 (t, 4H), 3.70-3.80 (m, 5H), 3.93 4.01 (m, 1H), 4.14-4.30 ( m, 2H), 4.95 (m, ÍH), 6.88 (s, ÍH), 6.99 (d, 2H), 7.40 (d, 2H), 8.81 (s, 1H). MS: ESP + (M + H) * = 445. Example 52: 5 (S) - (Isoxazol-3-ylaminomethyl) -3- (3, 5-difluoro- (4- (1- (2 (R, S)) -hydroxy-3-methylthiopropanoyl) -1,2,5,6-tetrahi-dropirid-4-yl) enyl) oxazolidin-2-one Reference Example 21 (300 mg, 0. 50 mM) in trifluoroacetic acid (2 ml) and dichloromethane (2 ml) and stirred for 15 minutes. The TFA was removed by azeotroping with toluene and the resulting residue was purified by Bond elute (silica Merck 9385, 60-100% EtOAc in hexane) to give the title compound as an off-white solid (200 mg, 80%). 1 H-NMR (300MHz, DMSO-d 6): d = 2.08 (s, 3H), 2.40 (m, 2H partially obscured by DMSO), 2.57, 2.79 (m, 2H partially obscured by DMSO), 3.24 (t, 2H) 3.29-3.84 (, 3H), 3.99-4.31 (m, 3H), 4.48 (m, ÍH), 4.88 (m, ÍH), 5.42 (m, 1H), 5.86 (s, ÍH), 5.98 (s, ÍH), 6.54 (t, ÍH), 7.33 (d, 2H), 8.38 (s, ÍH). MS: ESP * (M + H) * = 495. The starting material was prepared as follows: Reference Example 21: 5 (R) - (N-isoxazol-3-yl-N-terbutoxy-carbonyl) aminomethyl) - 3 (3, 5-difluoro- (4- (1- (2 (R, S) -hydroxy-3-methylthiopropanoyl) -1,2,5,6-tetrahydropyrid-4-yl) phenyl) oxazo-lidin-2 -one Reference Example 10 (1.00 g, 2.10 mM), 2-hydroxy-3- (methylthio) propionic acid (0.23 g, 1.68 mM), 1-hydroxybenzotriazole (0.29 g, 2.18 mM) and N-methylmorpholine (0.22 g) g, 2.18 mM), were recovered in DMF (5 ml), and 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (0.42 g, 2.18 M) was added.The resulting solution was stirred overnight. it was removed by evaporation and the residue was taken up in dichloromethane, washed with water, dried (MgSO.sub.4) and the solvent was reduced by evaporation, which was purified by MPLC (Merck silica 9385, 40-60% EtOAc in hexane). give the title compound as a pale yellow solid after trituration with diethylether (310 mg, 27%). 1H-NMR (300MHz, DMSO-d6): d = 1.48 (s, 9H), 2.18 (s, 3H), 2.39 (m, 2H partially obscured by DMSO), 2.57, 2.79 (m, 2H), 3.68-4.33 (m, 8H), 4.48 (m, ÍH), 5.01 (m, ÍH), 5.42 (dd, ÍH), 5.88 (s, ÍH), 6.84 (s, ÍH), 7.32 (d, 2H), 8.79 Cs, ÍH). MS: ESP * (M + H) * = 595. Example 53: 5 (S) - (Isoxazol-3-ylaminomethyl) -3- (3, 5-difluoro- (4- (1- (2 (R, S ) -hydroxy-3-methylsulfonylpropanoyl) -1,2,5,6-tetrahydropyrid-4-yl) enyl) oxazolidin-2-one Example 52 (188 mg, 0.38 mM) in dichloromethane (10 ml) was stirred at 0 ° C. ° C, and 3-chloroperoxybenzoic acid (57-86%, 0.22 g, 0.76 mM) was added in portions, the solution was stirred at 0 ° C for 3 hours, excess dichloromethane was added and this was washed with a solution of Saturated NaHC03, dried (MgSO4) and the solvent was removed by evaporation to give the title compound as a white powder after trituration with diethylether (60 mg, 30%). ^? - NMR (300MHz, DMSO-d6 ): d = 2.31 (m, 2H partially obscured by DMSO), 3.04 (s, 3H), 3.41 (m, 4H partially obscured by water), 3.52-3.87 (m, 3H), 3.91-4.37 (m, 3H) , 4.86 (m, 2H), 5.88 (s, ÍH), 5.99 (s, ÍH), 6.07 (d, ÍH), 6.56 (t, ÍH), 7.34 (d, 2H), 8.39 (s, ÍH). MS: ESP * (M + H) * = 527. Example 54: 5 (S) - (Isoxazol-3-yl-aminomethyl) -3- (3-fluoro- (4- (1- (2 (R, S) -hydroxy) 3-methylpropropanoyl) -1,2,5,6-tetrahydropy-rid-4-yl) phenyl) oxazolidin-2-one Reference Example 22 (290 mg 0.50 mM) was dissolved in trifluoroacetic acid (2 ml) and dichloromethane (2 ml) and stirred for 15 minutes The TFA was removed by azeotroping with toluene and the resulting residue was triturated to give the title compound as an off-white solid (150 mg, 63%). ^ - NMR (300MHz, DMSO-d6): d = 2.10 (s, 3H), 2.42 (m, 2H partially obscured by DMSO), 2.61, 2.81 (m, 2H partially obscured by DMSO), 3.43 (t, 2H partially obscured by water) 3.53- 3.87 (m, 3H), 4.02-4.39 (m, 3H), 4.50 (, 1H), 4.88 (quintet ÍH), 5.45 (broad, ÍH) 5.88 (s, ÍH), 6.02 (s, ÍH), 6.56 ( tH), 7.24-7.56 (m, 3H), 8.37 (s, ÍH) MS: ESP * (M + H) * = 477. The starting material was prepared as follows: Reference Example 22: 5 (R ) - (N-isoxazol-3-yl-N-terb utoxy-carbonyl) aminomethyl) -3- (3-fluoro- (4- (1- (2 (R, S) -hydroxy-3-methylthiopropanoyl) -1,2,5,6-tetrahydropyrid-4-yl) phenyl ) oxazo-lidin-2-one Hydrochloride of 5 (R) - (N-isoxazol-3-yl-N-terbutoxy-carbonyl) aminomethyl) -3- (3-fluoro-4- (1,2,5,6) -tetra-hydropyrid-4-yl) phenyl) oxazolidin-2-one (prepared in a manner analogous to Reference Example 10, but using 3-fluoro-substituted intermediates; 1.00 g, 2.02 mM), 2-hydroxy-benzotriazole (0.28 g, 2.10 mM) and N-methyl morpholine (0.22 g, 2.10 mM) recovered. in dichloromethane (5 ml), and hydrochloride 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide (0.40 2.10 mM). The resulting solution was stirred overnight. Excess dichloromethane was added and this was washed with water, dried (MgSO) and the solvent was reduced by evaporation. This was purified by MPLC (silica Merck 9385, 40-60% EtOAc in hexane) to give the title compound as a pale yellow solid after trituration with diethyl ether (300 mg, 26%). ^? - NMR (300MHz, DMSO-d6): d = 1.47 (s, 9H), 2.06 (s, 3H), 2.42 (m, 2H partially abscissed by DMSO), 2.58, 2.79 (m, 2H), 3e48- 4.32 (m, 8H), 4.48 (m, ÍH), 4.99 (m, ÍH), 5.39 (dd, ÍH), 6.02 (s, ÍH), 6.85 (s, 1H), 7.28-7.53 (m, 3H) 8.78 (s, 1H). MS: ESP * (M + H) * = 577.

Example 55: 5 (S) - (Isoxazol-3-yl-aminomethyl) -3- (3-fluoro- (4- (1- (2 (R, S) -hydroxy-3-methylsulfonylpropanoyl) -1,2, 5,6-tetrahydropyrid-4-yl) phenyl) oxazolidin-2-one Example 54 (140 mg, 0.29 mM) in dichloromethane (10 ml) was stirred and added in portions of 3-chloroperoxybenzoic acid (57-). 86%, 0.17 g, 0.76 mM) The solution was stirred for 3 hours, excess dichloromethane was added and this was washed with saturated NaHCO 3 solution, dried (MgSO 4) and the solvent was removed by evaporation and purified by bondelute. (silica Merck 9385, 70-100% EtOAc in hexane) to give the title compound as a white powder after trituration with diethyl ether (56 mg, 27%). H-NMR (300MHz, DMSO-d6): d = 2.41 (m, 2H partially obscured by DMSO), 3.02 (s, 3H "), 3.41 (m, 4H partially obscured by water), 3.49-3.86 (m, 3H), 3.86-4.36 (m, 3H), 4.72 - 4.95 (m, 2H), 5.95-6.10 (m, 3H), 6.54 (t, ÍH), 7.27-7.57 (m, 3H), 8.39 (s, ÍH) MS: ESP * (M + H) * = 509. Example 56: 5 (S) -Isoxazol-3-ylaminomethyl-3- [3-fluoro-4- (1- (2-phosphorylacetyl) -1, 2,5,6-tetrahydropyrid-4-yl) phenyl] oxazoli-din-2-one Trifluoroacetic acid (5.0 ml) was added dropwise at room temperature to a stirred solution of Reference Example 23 (250 mg, 0.41 mmol) in dichloroethane (5.0 ml). The resulting solution was stirred at room temperature for 10 minutes then evaporated to a pale yellow gum. Trituration with diethyl ether gave the title compound (200 mg, 98%) as a pale yellow solid. XH-NMR (300MHz, DMSO-d6) + CD3COOD): d = 2.30-2.50 (m, 2H), 3.40 (d, 2H), 3.52 (t) & 3.61 (t) (2H), 3.76 (dd, ÍH), 4.05 (m, 2H), 4.10 (t, ÍH), 4.51 (t, 2H), 4.77-4.90 (m, ÍH), 5.90-6.00 (m , 2H), 7.20-7.37 (m, 2H), 7.43 (d, ÍH), 8.30 (d, 1H). MS: ESP * (M + H) * = 497. The starting material was prepared as follows: Reference Example 23: 5 (S) -Isoxazol-3-ylaminomethyl-3- (3-fluoro-4- (1- (2-t-Butoxyphosphorylacetyl) -1,2,5,6-tetrahydropyrid-4-yl) phenyl) oxazolidin-2-one Di-tert-butyl N, N-diethylphosphoramidite (503 mg, 1.88 g) was added dropwise. mmoles) at room temperature, under a nitrogen atmosphere, to a stirred suspension of Example 5, (600 mg, 1.44 mmol) and lH-tetrazole (303 mg, 4.33 mmol) in tetrahydrofuran (20 ml). The resulting mixture was stirred for 1 hour, then an additional 224 mg of phosphoramidite was added and the reaction was stirred for 1.5 hours. The reaction was then cooled to -40 ° C and treated in portions with 3-chloroperoxybenzoic acid (750 mg, 70% strength, 3.0 mmol). The reaction was stirred at -40 to -20 ° C for 1 hour, then diluted with dichloromethane (60 ml), washed successively with 10% aqueous sodium bisulfite solution, saturated sodium bicarbonate solution and water, dried on magnesium sulfate and evaporated to give a colorless oil. Purified by flash chromatography (silica Merck 9385, 5% methanol / dichloromethane) to give the title compound (550 mg, 63%) as a colorless foam. XH-NMR (300MHz, DMSO-d6): d = 1.42 (s, 18H), 2.40-2.60 (m, 2H), 3.44 (t, 2H), 3.57 (t) & 3.66 (t) (2H), 3.81 (dd, ÍH), 4.10 (m, 2H), 4.16 (t, ÍH), 4.60 (t, 2H), 4.83-4.95 (m, ÍH), 5.95-6.05 (m, 2H), 6.56 (t, ÍH), 7.27-7.44 (m, 2H), 7. 50 (d, ÍH), 8.38 (d, ÍH). Example 57: 5 (S) -Isoxazol-3-yl-aminomethyl-3- (3, 5-difluoro-4- (1- (2 (S) -acetoxypropanoyl) -1,2,5,6-tetrahydropyrid-4 phenyl) oxazolidin-2-one Trifluoroacetic acid (2.0 ml) was added dropwise at room temperature to a stirred solution of Example Reference 24 (167 mg 0.28 mmol) in dichloromethane (2.0 ml). The resulting solution was stirred at room temperature for 30 minutes, then evaporated to a colorless gum. Trituration with diethyl ether gave the title compound (114 mg, 82%) as a colorless solid. ^ -H-NMR (300MHz, DMSO-d6): d = 1.27-1.40 (m, 3H), 2.05 (s, 3H), 2.24-2.50 (m, 2H), 3.42 (, 2H), 3.57-3.77 ( m, 2H), 3.81 (dd, ÍH), 3.95-4.10 (m, ÍH), 4.10-4.30 (m, 2H), 4. 84-4.96 (m, ÍH), 5.32-5.50 (m, ÍH), 5.87 (m, 1H), 6.00 (s, + ÍH), 6.56 (t, ÍH), 7.34 (d, 2H), 8.40 (s, ÍH). MS: ESP (M + H) * = 491. The starting material was prepared as follows: Reference Example 24: 5 (R) - (N-Isoxazol-3-yl-N-terbutoxy-carbonyl) aminomethyl-3- (3,5-difiuoro-4- (1- (2 (S) -acetoxypropanyl) ) -1, 2, 5, 6-tetrahydropyrid-4-yl) phenyl) -oxazolidin-2-one. (S) -2-Acehoxypropanoyl chloride (65 mg, 0.43 mmol) was added dropwise at room temperature to a suspension. Agitation of Reference Example 10 (200 mg, 0.39 mmol) and N, N-diisopropylethylamine (106 mg, 0.82 mmol) in dichloromethane (10 ml). The reaction was stirred at room temperature for 2 hours, then purified by flash chromatography (silica Merck 9385, ethyl acetate / iso-hexane (7/3)) to give the title compound (177 mg, 77%) as a colorless solid. ^? - NMR (300MHz, CDCI-d3): d = 1.45-1.52 (m, 3H), 1.57 (s, 9H), 2.14 (s, 3H), 2.42-2.62 (m, 2H), 3.69 (t, 2H), 3.80 (dd, ÍH), 3.93-4.20 (m, 2H), 4.20-4.26 (m, 2H), 4.37 (dd, ÍH), 5.04-5.16 (m, ÍH), 5.37-5.55 (m, ÍH), 5.81 (m) & 5.89 (m) (1H), 6.90 (s (br), ÍH), 7.16 (d, 2H), 8.27 (s, ÍH). MS: ESP * (M + H) * = 591. Example 58: 5 (S) -Isoxazol-3-yl-aminomethyl-3- (3, 5-difluoro-4- (1- (2 (S) -hydroxypropanoyl) - 1,2,5,6-tetrahydropyrid-4-yl) -phenyl) oxazolidin-2-one Example 57 (80 mg, 0.16 mmol) in 4.0 ml of a saturated solution of ammonia in methanol was stirred at room temperature for 18 hours, then the resulting clear solution was evaporated to a colorless gum. Trituration with diethyl ether gave the title compound (59 g, 80%) as a colorless solid. XH-NMR (300MHz, DMSO-d6): d = 1.20 (m, 3H), 2.20-2.45 (m, 2H), 3.40-3.65 (m, 2H), 3.72 (, 2H), 3.82 (dd, ÍH) , 3.98-4.37 (m, 3H), 4.40-4.45 (m, ÍH), 4.92 (m, 1H), 4.96 (d) & 5.03 (d) (ÍH), 5.88 (m, ÍH), 6.00 (s, ÍH), 6.55 (t, ÍH), 7.33 (d, 2H), 8.40 (s, ÍH). MS: ESP * (M + H) * = 449 Example 59: 3 (4- (1- ((2S) -2, 3-Dihydroxypropanoyl) -1, 2, 5, 6-tetrahydropyrid-4-yl) -3 , 5-difluorophenyl) -5 (S) - (3-methyliso-thiazol-5-ylaminomethyl) oxazolidin-2-one Using essentially the technique of Example 20, but starting from 3- (4- (1- ( 2, 2-dimethyl-1,3-dioxolan-4 (S) -ylcarbonyl) -1,2,5,6-tetrahydropyrid-4-yl) -3,5-difluorophenyl) -5 (R) -. { N- (t-butoxycarbonyl) -3-methylisothiazol-5-ylaminomethyl) oxazolidin-2-one (250 mg, 0.39 mM), and using a gradient increasing in polarity from 0 to 20% methanol in dichloromethane by chromatography, gave the desired product (92 mg). NMR (DMSO-d6): d = 2.16 (s, 3H); 2.29 (m, ÍH); 2.37 (m, 1H); 3.42 (t, 2H); 3.47 (m, ÍH); 3.55 (m, ÍH); 3.73 (m, ÍH); 3.76 (dd, ÍH); 4.10 (m, 2H); 4.14 (t, ÍH); 4.24 (m, ÍH); 4.36 (t, ÍH); 4.68 (t, ÍH); 4.87 (m, ÍH); 4.97 (m, ÍH); 5.86 (s, ÍH); 6.97 (s, ÍH); 7.31 (d, 2H); 7.38 (t, ÍH). MS (ESP): 495 (MH *) for C22H24F2N405S. Intermediates for this compound were prepared as follows: 3- (4- (1- (2, 2-Dimethyl-1,3-dioxolan-4 (S) -ylcarbonyl) -1,2,5,6-tetrahydropyrid-4 -yl) -3,5-difluorophenyl) -5 (R) - (N- (-butoxycarbonyl) -3-methylisothiazol-5-ylaminomethyl) oxazolidin-2-one The technique of the relevant intermediate for Example 20 was essentially used, but starting from 5- (t-butoxycarbonylamino) isothiazole (321 mg, 1.5 mM) as the amino component, gave the title product (221 mg). After chromatography on a 10 g Mega Bond Elut® silica column, the product was still impure, and returned to HPLC chromatography on a Hichrome 10 2.5 cm RPB column., eluting with a gradient of 0 to 100% acetonitrile in water containing 0.1% formic acid. The relevant fractions were combined to give the desired product (265 mg). MS (ESP): 635 (MH *) for C30H36F2? 4O7S 5- (fc-Butoxycarbonylamino) -3-methylisothiazole Using essentially the technique of the relevant intermediate for Example 20, but starting from 3-methyl-5-hydrochloride aminoisothiazole (1.5 g, 10 mM) as the amino component, gave the title product (950 mg) after chromatography. MS (ESP): 215 (MH *) for C9H? _4? 202S? MR (DMSO-d6: d = 1.46 (s, 9H); 2.23 (s, 3H); 6.50 (s, ÍH); 11.07 (br, ÍH).

Example 60: 3- (4- (1- (3-Hydroxypropanoyl) -1,2,5,6-tetrahydropyrid-4-yl) -3,5-difluorophenyl) -5 (S) - (isoxazol-3-ylaminomethyl) ) oxazolidin-2-one 3- (4- (1- (3-hydroxypropanoyl) -1,2,5,6-tetrahdropirid-4-yl) -3,5-difluorophenyl) -5 (R) - ( N- (-butoxycarbonyl) isoxazol-3-ylaminomethyl) oxazolidin-2-one (176 mg, 0.32 mM) in dichloromethane (1 ml) and treated with trifluoroacetic acid (1 ml) at room temperature. After stirring for 10 minutes, the mixture was diluted with water (15 ml) and dichloromethane (15 ml) the organic layer was separated, washed with water (2 x 15 ml), and dried (magnesium sulfate). The solvent was removed, and the residue was triturated with diethylether to give the desired product (102 mg). MR (DMSO-d6): d = 2.20 (m, ÍH); 2.28 (m, ÍH); 2.48 (m overlapped by DMSO, 2H); 3.42 (br m overlapped by H20, ~ 4H); 3.55 (br m, ~ 3H); 3.83 (t, ÍH); 4.01 (m, ÍH); 4.06 (m, 2H); 4.81 (m, 1H); 5.78 (s, ÍH); 5.92 (s, ÍH); 6.47 (br s, 1H); 7.26 (d, 2H); 8.31 (s, ÍH). MS (ESP): 449 (MH *) for C2? H22F2? 405 The intermediate for this compound was prepared as follows: 3- (4- (1- (3-Hydroxypropanoyl) -1,2,5,6-tetrahydropyridi- 4-yl) -3,5-difluorophenyl) -5 (R) - (N- (t-butoxycarbonyl) isoxazol-3-ylaminomethyl) oxazolidin-2-yone To a solution of 3-hydroxypropionic acid (45 mg, 0.5 mM) in N, N-dimethylformamide (2 ml) was added 3- (4- (1, 2, 5, 5-tetrahydropyrid-4-yl) -3,5-difluorophenyl) -5 (R) - hydrochloride ( N- (t-butoxycarbonyl) isoxazol-3-ylaminomethyl) oxazolidin-2-one (256 mg, 0.5 M, reference example 10), and 0-benzotriazole-1-yl-N, N, N ', N hexafluorosophosphate '-tetramethyluronium (190 mg, 0.5 mM). The mixture was cooled to 0 °, N / N-diisopropylethylamine (129 mg, 1 mM) was added and the mixture was stirred 18 hours, leaving the temperature to rise to room temperature. The mixture was poured into a mixture of ethyl acetate (40 'ml) and water (40 ml), the organic layer was separated and washed with aqueous sodium dihydrogen phosphate (2%, 40 ml), sodium bicarbonate (40 ml). ml) and brine (40 ml). The solvent was removed, and the residue was chromatographed on a 10 mg Mega Bond Elut® silica column eluting with a mixture of 2.5% methanol in dichloromethane. The relevant fractions were combined and evaporated to give the title product (203 mg). MR (DMSO-de): d = 1.47 (s, 9H); 2.28 (m, ÍH); 2.37 (m, ÍH); 2.54 (m overlapped by DMSO, 2H); 3.66 (br m, 4H); 3.86 (dd, ÍH); 3.95 (dd, ÍH); 4.08 (m, ÍH); 4.17 (m, ÍH); 4.26 (dd, 2H); 4.53 (m, ÍH); 5.02 (m, ÍH); 5.87 (s, ÍH); 6.86 (s, ÍH); 7.33 (d, 2H); 8.82 (s, ÍH). MS (ESP): 549 (MH +) for C26H30F2? 4O7 Example 61 _ The following illustrative representative pharmaceutical dosage forms containing a compound of the formula (I), an in vivo hydrolysable ester or a pharmaceutically acceptable salt thereof, including a pharmaceutically acceptable salt of a hydrolysable ester in vivo, (hereinafter Compound X), for therapeutic or prophylactic use in humans: (a) Tablet I mg / tablet Compound X 500 Lactose Ph.Eur 430 Croscaramellose sodium 40 Polyvinylpyrrolidone 20 Magnesium stearate 10 (b) Tablet II mg / tablet Compound X 100 Lactose Ph.Eur 179 Croscaramellose 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) Caps ula mg / capsule Compound X 10 Lactose Ph.Eur 389 Croscaramellose sodium 100 Magnesium stearate 1 (f) Injection I Compound X 50% w / v Isotonic aqueous solution up to 100% (g) Injection II (eg boluses) Compound X 10% w / v Isotonic aqueous solution up to 100% (h) Injection III Compound X 5% w / v Isotonic aqueous solution up to 100% (i) Injection IV (eg infusion) Compound X 1% w / v Isotonic aqueous solution up to 100% Shock absorbers, pharmaceutically acceptable surfactants, oils. or cosolvents such as polyethylene glycol, polypropylene glycol, glycerol, or ethanol, glidants (such as silicon dioxide) or complexing agents such as cyclodextrin (e.g., hydroxy-propyl-β-cyclodextrin or sulfo-butyl-ether-β-cyclodextrin) It can be used to help the formulation. Also, improvements in aqueous solubility, if desired, can be achieved, for example, together with a compound of the formula (I) with a phospholipid (such as a derivative of (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 & amp;; 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 Design "(Ed. Auton; Publisher: Churchill Livingstone, first published 19B8) Tablets (a) - (d) can be (polymer) coated by conventional means, for example to provide an enteric coating of cellulose acetate phthalate.

Claims (12)

1. A compound of the formula (I), or a pharmaceutically acceptable salt, or an in vivo hydrolysable ester thereof, (I) wherein HET is a 5-membered C-linked heteroaryl ring containing 2 to 4 heteroatoms independently selected from N, O and S, which ring is optionally substituted on an available carbon atom by 1 or 2 substituents independently selected from alkyl of C? -4, amino, C 1-4 alkylamino, C? -4 alkyl, C? -4 alkoxycarbonyl and halogen; and / or an available nitrogen atom (with the condition of the ring is therefore not quaternized) by alkyl of C? _4; or HET is a 6-membered C-linked heteroaryl ring containing 2 or 3 nitrogen heteroatoms, the ring of which is optionally substituted on any available C atom by 1, 2, or 3 substituents independently selected from C? -4 alkyl, amino, C 1-4 alkylamino, C 4 alkoxy, C 1 alkoxycarbonyl, 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 Ax is carbon or nitrogen; Bi is O or S (or, in Q9 only, NH); Xq is 0, S or N-R1 (wherein R1 is hydrogen, C4-4alkyl or hydroxyC1alkyl); and where in Q7 each Ai is independently selected from carbon or nitrogen, with a maximum of 2 nitrogen heteroatoms in the 6-membered ring, and Q7 is bound to T by any of the atoms Ai (where A 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 is bound to T by either of the carbon atoms specified in the 5-membered ring and bonded to the benzo ring by means of either the two carbon atoms specified on either side of the bond bonds shown; and Q9 is linked via either of the two specified carbon atoms on either side of the bond bond shown; where T is selected, from the groups in (TA) to (TD) 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 (OH) -, AR3-CH (0H) -; (TAc) AR1-CO, AR2-CO, AR3-CO, AR4-CO; (TAd) ARl-O-, AR2-0-, AR3-0-; (TAe) ARl S (0) q-, AR2-S (0) q-, AR3-S (O) 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? _4 alkoxy, C? _ alkanoyl, cyano, halo, trifluoromethyl, C? _4 NRvRw alkoxycarbonyl, C? _6 alkanoylamino, C? _4 alkoxycarbonylamino N-C 4 alkyl-N-alkanoylamino C 6 alkyl, C 4 -4 alkyl (0) q- (q is 0, 1 or 2), CY1, CY2 or AR1}; (TBb) -NRv1Rw1; (TBc) ethenyl, 2-C2-4 alkyletenyl, 2-cyanoethenyl, 2-cyano-2- (C4-4 alkyl) ethenyl, 2-nitro-tennyl, 2-nitro-2- (C4-4 alkyl) ethenyl, 2- (C 4 -4-alkylaminocarbonyl) ethenyl, 2- ((C 1 -4) alkenyl epentyl, 2- (AR 1) ethenyl, 2- (AR 2) ethenyl; (TBd) R 10 CO-, R 10 S (0) - (q is 0, 1 or 2) or R10CS- wherein R10 is selected from the following groups: - (TBda) CY1 or CY2; (TBdb) hydrogen, C3-4 alkoxycarbonyl, trifluoromethyl, -NRvRw, ethenyl, 2- (C 1 _4, 2-cyanoethenyl, 2-cyano-2- (C 4 alkyl) ethenyl, 2-nitro tenhenyl, 2-nitro-2- (C 4 alkyl) ethenyl, 2- ( C 1 _4) alkylaminocarbonyl, ethenyl, 2- (C 4 -4) alkenyl ethenyl, 2- (AR 1) ethenyl or 2- (AR 2) ethenyl; or (TBdc) C 4 alkyl, optionally substituted as was defined in (TBa) above, or by alkyl of C? _ 4S (0) pNH- or C? _4S (0) p- (C? -4 alkyl) N- (p is 1 or 2) alkyl}; wherein Rv is hydrogen or C? _4 alkyl; Rw is hydrogen or C- alkyl; Rv1 is hydrogen, C? _4 alkyl or C3_8 cycloalkyl; Rw1 is hydrogen, C? _4 alkyl, C3_8 cycloalkyl, C? _4-CO alkyl or C? _S 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 1 heteroatom selected from 0, N, and S (optionally oxidized), and linked by a nitrogen ring or sp3 carbon atom; (TCb) an optionally substituted 5-membered monocyclic ring containing 1 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 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 different from [where appropriate) in a bonded 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 5 or 6 membered ring system (bonded via 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 3-, 4- or 5-linked spiro carbon ring - members; whose bicyclic ring system is (i) fully saturated other than (where appropriate) at a bond sp2 carbon atom; (ü) 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-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 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 an O or S heteroatom, or an -N (RC) group on 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) C? -6 alkyl. { optionally substituted by one or more alkanoyl groups of C- (including geminal disubstitution) and / or optionally monosubstituted by cyano, C? -4 alkoxy, trifluoromethyl, C? _4 alkoxycarbonyl, phenyl (optionally substituted as AR defined in the following) , alkyl of C_4S (O) 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 [ wherein Rv is hydrogen or C? _4 alkyl; Rw is hydrogen or C? -4 alkyl, C? _6 alkanoylamino, C? -4 alkoxycarbonylamino, C? _4-N-C3-4 alkanoylamino N-alkyl, C? _4S alkyl (0) ) pNH- or alkyl of C? _4S (O) p- (C? _4 alkyl) N- (p is 1 or 2)}; (Rc2) R13C0-, R13S02 or R13CS- wherein R13 are selected from (Rc2a) to (Rc2e): - (Rc2a) AR1, AR2, AR2a, AR2b, AR3, AR3a, AR3b, AR4, AR4a, CYl, CY2; (Rc2b) hydrogen, C? _4 alkoxycarbonyl, trifluoromethyl, -NRvRw [wherein Rv is hydrogen or C? -4 -4 alkyl, - Rw is hydrogen or C? _4 alkyl], ethenyl, 2-alkyletenyl of C? _4 , 2-cyanoethenyl, 2-cyano-2- (C 4 -4 alkyl) ethenyl, 2-nitro-ethenyl, 2-nitro-2- (C 1 -4 alkyl) ethenyl, 2- (C 1 -4 alkylaminocarbonyl) ethenyl, 2- (C 4 -4 alkoxy) ethenyl, 2- (AR 1) ethenyl, 2- (AR 2) ethenyl, 2- (AR 2a) ethenyl; (Rc2c) C? -? O alkyl. { optionally substituted by one or more groups (including geminal disubstitution) each independently selected from hydroxy, C? -? o alkoxy, C? -4 alkoxy from C? _, C? -4-alkoxy from C? ? -4 C-4 alkoxy?, C 1-4 alkanoyl, phosphoryl [-OP (O) (OH) 2, and C 1-4 mono- and di-alkoxy derivatives thereof], phosphoryl [-0-P (OH) 2 and mono derivatives - and di-C 1-4 alkyl thereof], and amino and / or optionally substituted by a group selected from phosphonate [phosphono, -P (0) (OH) 2, and mono- and di-alkoxy derivatives of C? _4 thereof], phosphinate [-P (OH) 2 and mono- and di-alkoxy derivatives of C? -4 thereof], cyano, halo, trifluoromethyl, alkoxycarbonyl of C? _4, alkoxy of C? _4-C4_4alkoxycarbonyl, C4_4alkoxy C1-4alkoxy-C4_4alkoxycarbonyl, C4_4alkylamino, di (C_4_4alkyl) amino, C_alkylaminoalkylamino; _6, C4_4alkoxycarbonylamino, C_4-N-C3_6alkanoylamino N-alkyl, C4_4alkylaminocarbonyl, di (C1_4alkyl) aminocarbonyl, C1-4S_alkynyl ) PNH-, C? -4S (0) p- (C? _4) N- alkyl, C? _4S (0) PNH-, fluoroalkyl of C? _4S (0) p- (alkyl) C? _4) N-, C? _4S alkyl (0) q-, [the C? -4 alkyl group of C? _4S (0) alkyl which is optionally substituted by a substituent selected from hydroxy, C? -4 alkoxy, C 1-4 alkanoyl, phosphonyl [-0-P (0) (0H) 2 and mono- and di-alkoxy derivatives of C ?- 4 of them], phosphoryl [-0-P (OH) 2 and mono- and di-alkoxy derivatives of C 1-4 thereof], amino, cyano, halo, trifluoromethyl, alkoxycarbonyl of C? _4, alkoxy of C 4 -4 alkoxycarbonyl of C 4 -C 4 alkoxy C 1 -4 alkoxy of C 4 -4 alkoxycarbonyl, carboxy, C 4 alkylamino, C 4 -4 dialkyl, amino, C 1 alkylamino ? 6, C? -4 alkoxycarbonylamino, C? -4-N-alkanoylamino of C? -6 alkyl, C? - alkylaminocarbonyl, dialkyl of C? _4, aminocarbonyl, C? -S alkyl (O ) NH-, alkyl of C? _4S (0) p- (C? -4 alkyl) N-, alkyl of C? -4S (0) q-, AR1-S (0) q, AR2-S (0 ) q-, AR3-S (0) q, and also versions AR2a, AR2b, AR3a and AR3b of groups containing AR2 and AR3}; CYl, CY2, ARl, AR2, AR3, ARl-O-, AR2-0-, AR3-0-, AR1-S (0) q-, AR3-S (0) q-, ARl-NH-, AR2- NH-, AR3-NH- (P is 1 or 2 and q is 0, 1, or 2), and also versions AR2a, AR2b, AR3a and AR3b of the groups containing AR2 and AR3}; (Rc2d) R14C (O) Oalkyl of C? _6 where R14 is ARl, AR2, C4_4 alkylamino (the C4_4 alkyl group which is optionally substituted by alkoxycarbonyl or by carboxy), benzyloxyC_4_alkyl or C_4_alkyl. { optionally substituted as defined by (Rc2c)}; (Rc2e) R150- wherein R15 is benzyl, C4 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- (C4-4) ethenyl alkoxycarbonyl, -nitroetenyl, 2-nitro-2- (C? _4 alkyl) ethenyl, 2- (Al) ethenyl, (AR2) eteni lo, or of the formula (Rc3a) (Rc3a) wherein X00 is -OR17, -SR17, -NHR17 and -N (R17) 2; wherein R17 is hydrogen (when X00 is -NHR17 and -N (R17) 2), and R17 is C? _4 alkyl, phenyl or AR2 (when X00 is -OR17, -SR17 and -NHR17); and R16 is cyano, nitro, C? -4 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; e is hydrogen or C? _6 alkyl, or Rd and Re together form an alkylene chain of C4; Rf is hydrogen, C6_6alkyl, C6_6 hydroxyalkyl, C6_6alkyl, C6_6alkyl, NRvRw [wherein Rv is hydrogen or C4_4alkyl; Rw is hydrogen or C? -4 ]alkyl], C alco _alkoxy, C? _6alkyl alkoxy, C2_6 hydroxyalkoxy, C2_6 alkylamino C 2 -C 6 alkoxy, C dial-C alco alkoxy dialkylamino; 6, "Rg is C alquilo-βalkyl, hydroxy or C?-6alkoxy, Rh is hydrogen or Ci-βalkyl," Ri is hydrogen, C? _6alkyl, ARl, 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 (ie with the maximum degree of unsaturation) containing up to four heteroatoms independently selected from 0, N, and S (but not containing any of the 0-0 bonds) , 0-S or SS), and linked by means of a ring of carbon atom or a ring of nitrogen 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 bicyclic heteroaryl ring of 8, 9 or 10 members, completely unsaturated (ie with the maximum degree of unsaturation) containing up to four heteroatoms independently selected from 0, N and S (but not containing any of the 0 bonds). -0, 0-S or SS), 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 completely, degree of unsaturation), bound by a ring of carbon atom, or linked by means of a nitrogen atom in the ring if the ring is therefore not 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 joined by means of 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 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. 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 T is an optionally substituted N-linked heteroaryl ring system (fully unsaturated) of 5 members containing 1, 2 or 3 nitrogen atoms, is preferably selected from a group of the formula. { TAfl) a (TAfß): (TAf4) (TAf5) (TAf6) where: R6 is selected (independently where appropriate) from hydrogen, C? _4alkyl, C? _4alkoxycarbonyl, C? _4alkanoyl, carbamoyl and cyano; R4 and R5 are independently selected from hydrogen, halo, trifluoromethyl, cyano, nitro, C4-4 alkoxy, C4-4S alkyl (0) q- (q is 0, 1 or 2), C1-4 alkanoyl, alkoxycarbonyl of C? -. 4, C2-4 alkanoyloxy-C? _4 alkyl, benzoxy-C? -alkyl, C2_4-alkanoylamino, -CONRvRw, -NRvRw and C? _ 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 1-4 alkyl; Rw is hydrogen or C1-4 alkyl}; or R4 is selected from one of the following groups in (TAfa) to (TAfc), 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 give the groups in (TAfa) to (TAfc) following: (TAfa) a group of the formula (TAf to) (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, C? _4S alkyl (O) q- (q is 0, 1 or 2), RvRwNS02- trifluoromethyl, pentafluoroethyl, C? _4 alkanoyl and -CONRvRw [wherein Rv is hydrogen or C? _ 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 with up to three substituents independently selected from C? _, cyano, trifluoromethyl, nitro, halo and alkylsulfonyl alkyl of Cl-4, "(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; where X1 is a direct link to. -CH (OH) - and Y1 is - (CH2) m-, - (CH2) n -NH- (CH2) m, -CO- (CH2) m-CONH- (CH2) m-, -C (= S ) NH- (CH2) m- or -C (= 0) 0- (CH2) m-; or wherein X1 is - (CH2) - or - CH (Me) - (CH2) m and Y1 is - (CH2) m -NH- (CH2) m-, -CO- (CH2) m-, CONH- (CH2) ) m-, -C (= S) NH- (CH2) m-, -C (= 0) 0- (CH2) m- O -S (O) q- (CH2) m-; or where X1 is -CH20-, -CH2NH- or -CH2N (alkyl C? -4) - 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 (C? _4 alkyl) - and Y1 is - (CH2) m- where X1 is -CH20- or -CH2N C? _4- alkyl; where n is 1, 2 or 3; m is 0, 1, 2 or 3 and q is 0, 1 or 2; and wherein Y1 is - (CH2) m- NH- (CH2) m- each m is independently selected from 0, 1, 2 or 3. 3. A compound of the formula (I), or a pharmaceutically acceptable salt, or a hydrolysable ester thereof, according to claim 1, wherein T is a bicyclic ring system of 7-, o- or 9-members containing a bridge of 1, 2 or 3 carbon atoms (group (TDb)) selected from a group defined by the ring skeletons shown in formula (TDbl) a (TDbl4): - 7-member ring skeletons [4,1,0] [3,2,0] [3,1,1] [

2.2 , 1] (TDbl) (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) (TDb8) (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 O or S ring heteroatom), and when the nitrogen ring is present, the heteroatom / heteroatoms O 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 carbon atoms in the ring at 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 one position] bridgehead], > C (H) -NHRc, > C (H) -NRc-C-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? _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 (in addition) substituted on a ring of carbon atom available by the bicyclic spiro ring systems described in (TDa); wherein Rc has any of the listed values according to claim 1.

4. A compound of the formula (I), or a pharmaceutically acceptable salt, or a hydrolysable ester thereof, according to claim 1, characterized in that is (TC) (groups (TCa) a (TCc)) and is defined by the formula (TC1) to (TC4): - (TC1) (TC2) (TC3) (TC4) where in (TC1): > A3-B3- es > C (Rq) -CH (Rr) - and G is -0-, -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 -O-, -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 -O-, -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 -O-, -S-, -SO-, -S02- or > N (Rc); R p is hydrogen, C 4 -4 alkyl (different when such substitution is defined by > A3-B 3 -), hydroxy, C 4 alkoxy or C 4 alkanoyloxy; where in (TC1.), (TC2) and (TC4); ml, ni and ol are as defined in the above: > A -B3- is > N-CH2- and G is > C (R1: l) (R12), > C = 0, > C-OH, > C-4 C-alkoxy, > C = N-OH, > C = N-alkoxy of C? -4, > C = N-NH-alkyl of C? _4, > C = NN ((C 1 4 alkyl) 2 (the latter two C 4 -alkyl groups above in G being optionally substituted by hydroxy) or > C = NN-C0-C alco alkoxy; where > represents two single bonds: Rq is hydrogen, hydroxy, halo, C? -4 alquiloalkyl or C alca _ alca alkanoyloxy, Rr is (independently where appropriate) hydrogen or C alquilo _alkyl; R11 is hydrogen, alkyl of C? _4, fluoroalkyl of C? -4, alkyl of C? _4-thio-alkyl of C? - or hydroxy-alkyl of C? _4 and R12 is - [C (Rr) (Rr)] m2-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 link in >A3- up to two substituents independently selected from C? _4 alkyl, C? _4 fluoroalkyl (including trifluoromethyl), C? _4-thiol-C? _4 alkyl, hydroxy-C? -4 alkyl, amino, amino-C de- alkyl, C?-alkanoylamino, C? _4-alkanoylamino-C alquilo -4-alkyl, carboxy, C? -4 alco 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 -O- or -S-); wherein AR is optionally substituted phenyl, optionally substituted C 4 _4 phenylalkyl, optionally substituted naphthyl, optionally substituted 5- or 6-membered heteroaryl; optionally substituted 5/6 or 6/6 bicyclic heteroaryl ring system, in which the bicyclic heteroaryl ring systems can be attached via an atom in either of the rings comprising the bicyclic system, and wherein the systems of bicyclic heteroaryl ring are attached by means of a carbon atom in the ring and can be (partially hydrogenated); and wherein Rc is as defined in claim 1.

5. The compound of the formula (I), or a pharmaceutically acceptable salt, or an in vivo hydrolysable ester according to claim 1 and 4, characterized in that T is ( in the groups in (TCa) to (TCc) defined by the formulas (TC5) to (TC11): - (TC5) (TC6) (TC7) (TC8) (TC9) (TOO) (TC11) wherein Rc is as defined in accordance with claim 1.

6. The compound of the formula (I) according to claim 1, characterized in that it is a compound of the formula (IC), or a pharmaceutically acceptable salt, or an in vivo hydrolysable ester thereof (CI) where TSH is isoxazol-3-yl, isoxazol-5-yl, 1,2-oxadiazol-3-yl, isothiazol-3-yl, 1,2-thiadiazol-3-yl or 1,2 , 5- thiadiazol-3-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, naphthyl, furan, pyrrole, pyrazole, imidazole, triazole, pyrimidine, pyridazine, pyridine, isoxazole, oxazole, isothiazole, thiazole or thiophene), C? _4 alkyl, carboxy, C? _4 alkoxycarbonyl, hydroxymethyl, C? _4 alkoxymethyl or carbamoyl and Rep is cyano, pyrimidin-2-yl, 2-cyanohetenyl, 2-cyano-2-alkyl of C? _-ethenyl or Rep is of the formula R10pCO-, R10pSO2- or R10pCS- (wherein R10p is hydrogen, C1-5 alkyl [optionally substituted by one or more groups each independently selected from hydroxy and amino, optionally monosubstituted by C? -4 alkoxy, C? _4S (0) q- alkyl, C? _4 alkylamino, C? _4 alkanoyl, naphthoxy, C 2-6 alkanoylamino or C? -4S (0) pNH- alkyl wherein 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, talazine, cinnoline naphidine, or R 10p is of the formula RllpC (O) Oalkyl of C? -6 wherein Rllp is C? _6 alkyl, or Rep is of the formula RfC (= 0) C (= 0) - wherein Rf is C? _g alkoxy; or pharmaceutically acceptable salts thereof. The compound according to claim 1, characterized in that: 5 (S) -Isoxazol-3-ylaminomethyl-3- (3-fluoro-4- (3,6-dihydro- (2H) -piran-4-yl) Phenyl) oxazolidin-2-one; 5 (S) -Isoxazol-3-ylaminomethyl-3- (3-fluoro-4-morpholinophenyl) -oxazolidin-2-one; 5 (S) -Isoxazol-3-ylaminomethyl-3- [3-fluoro-4- (1-hydroxyacetyl-1,2,5,6-tetrahydropyrid-4-yl) phenyl] oxazolidin-2-one; 5 (S) -Isoxazol-3-ylaminomethyl-3- [3-fluoro-4- (1- (2 (S), 3-dihydroxypropanoyl) -1,2,5,6-tetrahydropyrid-4-yl) phenyl] oxazolidin-2-one; 5 (S) -Isoxazol-3-ylaminomethyl-3- (3,5-difluoro-4- (1-hydroxyacetyl-1, 2,5,6-tetrahydropyrid-4-yl) phenyl) oxazolidin-2-one; 5 (S) -Isoxazol-3-ylaminomethyl-3- (3, 5-difluoro-4- (1- (2 (S), 3-dihydroxypropanoyl) -1,2,5,6-tetrahydropyrid-4-yl) phenyl] oxazolidin-2-one; 5 (S) -Isoxazol-3-ylaminomethyl-3- (1-hydroxyacetyl-1,2,5,6-tetrahydropyrid-4-yl) phenyl] oxazolidin-2-one; S) -Isoxazol-3-ylaminomethyl-3- (1- (2 (S), 3-dihydroxypropanoyl) -1,2,5,6-tetrahydropyrid-4-yl) phenyl] oxazolidin-2-one; or a salt pharmaceutically acceptable or an in vivo hydrolysable ester thereof 8. A process for the preparation of a compound of the formula (I) according to claim 1, or pharmaceutically acceptable salts or in vivo hydrolysable esters thereof, wherein the process of (a) to (d); - (a) modifying a substituent on or introducing a substituent into other compound of the formula (I); (b) by the reaction of a compound of the formula (II) if) where Y is either (i) hydroxy; or (ii) a dispersible group with a compound of the formula (III): HN (Pg) -HET (III) wherein Pg is a suitable protecting group; or (c) by reacting a compound of the formula (IV): Q-Z (IV) wherein Z is an isocyanate, amine or urethane group with an epoxide of the formula (V): (V) (d) by reacting a compound of the formula (II) wherein Y is an amino group with a compound of the formula (IIIA): Lg-HET (IIIA) wherein Lg is a leaving group; ~ and therefore if necessary: (i) eliminate any protective groups; (ii) forming a pharmaceutically acceptable salt; (iii) forming a hydrolysable ester in vivo. 9. The method for producing an antibacterial effect in a warm-blooded animal which comprises administering to the animal an effective amount of a compound of the formula (I) according to claims 1 to 7, or a pharmaceutically acceptable salt, or a in-vivo hydrolysable ester thereof. The method of formula (I) according to claims 1 to 7, or a pharmaceutically acceptable salt, or an in-vivo hydrolysable ester thereof, for one as a medicament. 11. The use of a compound of the formula (I) according to claims 1 to 7, or a pharmaceutically acceptable salt, or an 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. 12. The pharmaceutical composition comprising a compound of the formula (I) according to claims 1 to 7, or a pharmaceutically acceptable salt, or an in-vivo hydrolysable ester thereof, and a pharmaceutically acceptable diluent or carrier.