CA2405349A1 - Oxazolidinone derivatives with antibiotic activity - Google Patents

Oxazolidinone derivatives with antibiotic activity Download PDF

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CA2405349A1
CA2405349A1 CA002405349A CA2405349A CA2405349A1 CA 2405349 A1 CA2405349 A1 CA 2405349A1 CA 002405349 A CA002405349 A CA 002405349A CA 2405349 A CA2405349 A CA 2405349A CA 2405349 A1 CA2405349 A1 CA 2405349A1
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alkyl
ring
optionally substituted
alkoxy
ethenyl
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CA2405349C (en
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Michael Barry Gravestock
Michael John Betts
David Alan Griffin
Ian Richard Matthews
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AstraZeneca AB
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Astrazeneca Ab
Michael Barry Gravestock
Michael John Betts
David Alan Griffin
Ian Richard Matthews
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
    • C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
    • C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
    • C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
    • C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/10—Spiro-condensed systems

Abstract

Compounds of formula (I), or a pharmaceutically-acceptable salt, or an in-vivo-hydrolysable ester thereof, wherein HET is an N-linked 5-membered heteroaryl ring, optionally substituted on a C atom by an oxo or thioxo group; and/or by 1 or 2(1-4C) alkyl groups; and/or on an available nitrogen atom by (1-4C)alkyl; or HET is an N-linked 6-membered heteroaryl ring containing up to three nitrogen heteroatoms in total, optionally substituted on a C atom as above; Q is selected from, for example, (Q1), R2 and R3 are independently hydrogen or fluoro; T is selected from a range of groups, for example, 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.

Claims (13)

1. A compound of the formula (I), or a pharmaceutically-acceptable salt, or an in-vivo-hydrolysable ester thereof, wherein HET is an N-linked 5-membered heteroaryl ring, containing either (i) 1 to 3 further nitrogen heteroatoms or (ii) a further heteroatom selected from O and S together with an optional further nitrogen heteroatom; which ring is optionally substituted on a C atom by an oxo or thioxo group; and/or the ring is optionally substituted on a C atom by 1 or 2 (1-4C)alkyl groups; and/or on an available nitrogen atom (provided that the ring is not thereby quaternised) by (1-4C)alkyl; or HET is an N-linked 6-membered heteroaryl ring containing up to three nitrogen heteroatoms in total (including the linking heteroatom), which ring is substituted on a suitable C atom by oxo or thioxo and optionally substituted on any available C atom by 1 or 2 (1-4C)alkyl substituents;

Q is selected from Q1 to Q9 :- wherein R2 and R3 are independently hydrogen or fluoro;
wherein A, is carbon or nitrogen; B1, is O or S (or, in Q9 only, NH); Xq is O, S or N-R1 (wherein R1 is hydrogen, (1-4C)alkyl or hydroxy-(1-4C)alkyl); and wherein in Q7 each A, is independently selected from carbon or nitrogen, with a maximum of 2 nitrogen heteroatoms in the 6-membered ring, and Q7 is linked to T via any of the A1 atoms (when A1, is carbon), and linked in the 5-membered ring via the specified carbon atom, or via A1 when A1 is carbon; Q8 is linked to T via either of the specified carbon atoms in the 5-membered ring, and linked in the benzo-ring via either of the two specified carbon atoms on either side of the linking bond shown; and Q9 is linked via either of the two specified carbon atoms on either side of the linking bond shown;

wherein T is selected from the groups in (TA) to (TD) below (wherein AR1, AR2, AR2a, ARZb, AR3, AR3a, AR3b, AR4, AR4a, CY1 and CY2 are defined hereinbelow);
(TA) T is selected from the following groups :-(TAa) AR1, AR1-(1-4C)alkyl-, AR2 (carbon linked), AR3;
(TAb) AR1-CH(OH), AR2-CH(OH)-, AR3-CH(OH)-;
(TAc) AR1-CO-, AR2-CO-, AR3-CO-, AR4-CO-;
(TAd) AR1-O-, AR2-O-, AR3-O-;
(TAe) AR1-S(O)q- , AR2-S(O)q- , AR3-S(O)q- (q is 0, 1 or 2);

(TAf) an optionally substituted N-linked (fully unsaturated) 5-membered heteroaryl ring system containing 1, 2 or 3 nitrogen atoms;
(TAg) a carbon linked tropol-3-one or tropol-4-one, optionally substituted in a position not adjacent to the linking position; or (TB) T is selected from the following groups :-(TBa) halo or (1-4C)alkyl {optionally substituted by one or more groups each independently selected from hydroxy, (1-4C)alkoxy, (1-4C)alkanoyl, cyano, halo, trifluoromethyl, (1-4C)alkoxycarbonyl, -NRvRw, (1-6C)alkanoylamino, (1-4C)alkoxycarbonylamino, N-(1-4C)alkyl-N-(1-6C)alkanoylamino, (1-4C)alky1S(O)q- (q is 0, 1 or 2), CY1, CY2 or AR1 };
(TBb) -NRv1Rw1 ;
(TBc) ethenyl, 2-(1-4C)alkylethenyl, 2-cyanoethenyl, 2-cyano-2-((1-4C)alkyl)ethenyl, 2-nitroethenyl, 2-nitro-2-((1-4C)alkyl)ethenyl, 2-((1-4C)alkylaminocarbonyl)ethenyl, 2-((1-4C)alkoxycarbonyl)ethenyl, 2-(AR1)ethenyl, 2-(AR2)ethenyl;
(TBd) R10-CO- , R10S(O)q (q is 0, 1 or 2) or R10CS-wherein R10 is selected from the following groups :-(TBda) CY1 or CY2;
(TBdb) hydrogen, (1-4C)alkoxycarbonyl, trifluoromethyl, -NRvRw, ethenyl, 2-(1-4C)alkylethenyl, 2-cyanoethenyl, 2-cyano-2-((1-4C)alkyl)ethenyl, 2-nitroethenyl, 2-nitro-2-((1-4C)alkyl)ethenyl, 2-((1-4C)alkylaminocarbonyl)ethenyl, 2-((1-4C)alkoxycarbonyl)ethenyl, 2-(AR1)ethenyl or 2-(AR2)ethenyl; or (TBdc) (1-4C)alkyl {optionally substituted as defined in (TBa) above, or by (1-4C)alkylS(O)p NH- or (1-4C)alkylS(O)p-((1-4C)alkyl)N- (p is 1 or 2)};
wherein Rv is hydrogen or (1-4C)alkyl; Rw is hydrogen or (1-4C)alkyl; Rv1 is hydrogen, (1-4C)alkyl or (3-8C)cycloalkyl; Rw1 is hydrogen, (1-4C)alkyl, (3-8C)cycloalkyl, (1-4C)alkyl-CO- or (1-4C)allcylS(O)q- (q is 1 or 2); or (TC) T is selected from the following groups :-(TCa) an optionally substituted, fully saturated 4-membered monocyclic ring containing 1 heteroatom selected from O, N and S (optionally oxidised), and linked via a ring nitrogen or sp3 carbon atom;
(TCb) an optionally substituted 5-membered monocyclic ring containing 1 heteroatom selected from O, N and S (optionally oxidised), and linked via a ring nitrogen atom or a ring sp3 or sp2 carbon atom, which monocyclic ring is fully saturated other than (where appropriate) at a linking sp2 carbon atom;
(TCc) an optionally substituted 6- or 7-membered monocyclic ring containing 1 or 2 heteroatoms independently selected from O, N and S (optionally oxidised), and linked via a ring nitrogen atom or a ring sp3 or sp2 carbon atom, which monocyclic ring is fully saturated other than (where appropriate) at a linking sp2 carbon atom; or (TD) T is selected from the following groups :-(TDa) a bicyclic spiro-ring system containing 0, 1 or 2 ring nitrogen atoms as the only ring heteroatoms, the structure consisting of a 5- or 6-membered ring system (linked via a ring nitrogen atom or a ring sp3 or sp2 carbon atom) substituted (but not adjacent to the linking position) by a 3-, 4- or 5-membered spiro-carbon-linked ring; which bicyclic ring system is (i) fully saturated other than (where appropriate) at a linking sp2 carbon atom;
(ii) contains one -N(Rc)- group in the ring system (at least two carbon atoms away from the linking position when the link is via a nitrogen atom or an sp2 carbon atom) or one -N(Rc)-group in an optional substituent (not adjacent to the linking position) and is (iii) optionally further substituted on an available ring carbon atom; or (TDb) a 7-, 8- or 9-membered bicyclic ring system (linked via a ring nitrogen atom or a ring sp3 or sp2 carbon atom) containing 0, 1 or 2 ring nitrogen atoms (and optionally a further O or S ring heteroatom), the structure containing a bridge of 1, 2 or 3 carbon atoms; which bicyclic ring system is (i) fully saturated other than (where appropriate) at a linking sp2 carbon atom;
(ii) contains one O or S heteroatom, or one -N(Rc)- group in the ring (at least two carbon atoms away from the linking position when the link is via a nitrogen atom or an sp2 carbon atom) or one -N(Rc)- group in an optional substituent (not adjacent to the linking position) and is (iii) optionally further substituted on an available ring carbon atom;

wherein Rc is selected from groups (Rc1) to (Rc5) :-(Rc1) (1-6C)alkyl {optionally substituted by one or more (1-4C)alkanoyl groups (including geminal disubstitution) and/or optionally monosubstituted by cyano, (1-4C)alkoxy, trifluoromethyl, (1-4C)alkoxycarbonyl, phenyl (optionally substituted as for AR defined hereinafter), (1-4C)alkylS(O)q- (q is 0, 1 or 2); or, on any but the first carbon atom of the (1-6C)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 (1-4C)alkyl; Rw is hydrogen or (1-4C)alkyl], (1-6C)alkanoylamino, (1-4C)allcoxycarbonylamino, N-(1-4C)allcyl-N-(1-6C)all~anoylamino, (1-4C)alkylS(O)pNH- or (1-4C)allcylS(O)p-((1-4C)allcyl)N-(p is 1 or 2));
(Rc2) R'3C0- , R'3SOZ- or R13CS-wherein R'3 is selected from (Rc2a) to (Rc2e) :-(Rc2a) AR1, AR2, ARZa, ARZb, AR3, AR3a, AR3b, AR4, AR4a, CYl, CY2;
(Rc2b) hydrogen, (1-4C)alkoxycarbonyl, trifluoromethyl, -NRvRw [wherein Rv is hydrogen or (1-4C)allcyl; Rw is hydrogen or (1-4C)allcyl], ethenyl, 2-(1-4C)allcylethenyl, 2-cyanoethenyl, 2-cyano-2-((1-4C)allcyl)ethenyl, 2-nitroethenyl, 2-nitro-2-((1-4C)alkyl)ethenyl,
2-((1-4C)allcylaminocarbonyl)ethenyl, 2-((1-4C)alkoxycarbonyl)ethenyl, 2-(ARl)ethenyl, 2-(AR2)ethenyl, 2-(AR2a)ethenyl;
(Rc2c) (1-lOC)alkyl f optionally substituted by one or more groups (including geminal disubstitution) each independently selected from hydroxy, (1-lOC)alkoxy, (1-4C)alkoxy-(1-4C)alkoxy, (1-4C)all~oxy-(1-4C)alkoxy-(1-4C)allcoxy, (1-4C)alkanoyl, phosphoryl [-O-P(O)(OH)z, and mono- and di-(1-4C)alkoxy derivatives thereofJ, phosphiryl [-O-P(OH)2 and mono-and di-(1-4C)alkoxy derivatives thereofJ, and amino; and/or optionally substituted by one group selected from phosphonate [phosphono, -P(O)(OH)2, and mono- and di-(1-4C)alkoxy derivatives thereof], phosphinate [-P(OH)z and mono- and di-(1-4C)all~oxy derivatives thereo f , cyano, halo, trifluoromethyl, (1-4C)allcoxycarbonyl, (1-4C)allcoxy-(1-4C)alkoxycarbonyl, (1-4C)alkoxy-(1-4C)alkoxy-(1-4C)alkoxycarbonyl, (1-4C)alkylamino, di((1-4C)alkyl)amino, (1-6C)alleanoylamino, (1-4C)all~oxycarbonylamino, N-(1-4C)allcyl-N-(1-6C)alkanoylamino, (1-4C)alkylaminocarbonyl, di((1-4C)allcyl)aminocarbonyl, (1-4C)alkylS(O)pNH-, (1-4C)alkylS(O)p-((1-4C)alkyl)N-, fluoro(1-4C)allcylS(O)pNH-, fluoro(1-4C)alkylS(O)p((1-4C)alkyl)N-, (1-4C)alkylS(O)q- [the (1-4C)alkyl group of (1-4C)alkylS(O)q- being optionally substituted by one substituent selected from hydroxy, (1-4C)alkoxy, (1-4C)alkanoyl, phosphoryl [-O-P(O)(OH)2, and mono- and di-(1-4C)allcoxy derivatives thereof], phosphiryl [-O-P(OH)2 and mono- and di-(1-4C)alkoxy derivatives thereof], amino, cyano, halo, trifluoromethyl, (1-4C)alkoxycarbonyl, (1-4C)alkoxy-(1-4C)alkoxycarbonyl, (1-4C)alkoxy-(1-4C)alkoxy-(1-4C)allcoxycarbonyl, carboxy, (1-4C)alkylamino, di((1-4C)alkyl)amino, (1-6C)alkanoylamino, (1-4C)alloxycarbonylamino, N-(1-4C)alkyl-N-(1-6C)alkanoylamino, (1-4C)alkylaxninocarbonyl, di((1-4C)alkyl)aminocarbonyl, (1-4C)alkylS(O)p NH-, (1-4C)alkylS(O)p-((1-4C)alkyl)N-, (1-4C)alkylS(O)q-, AR1-S(O)q-, AK2-S(O)q- , AR3-S(O)q- and also AR2a, AR2b, AR3a and AR3b versions of AR2 and AR3 containing groups], CY1, CY2, AR1, AR2, AR3, AR1-O-, AR2-O-, AR3-O-, AR1-S(O)q-, AR2-S(O)q-, AR3-S(O)q-, AR1-NH-, AR2-NH-, AR3-NH-(p is 1 or 2 and q is 0, 1 or 2), and also AR2a, AR2b, AR3a and AR3b versions of AR2 and AR3 containing groups;

(Rc2d) R14C(O)O(1-6C)alkyl wherein R14is AR1, AR2, (1-4C)alkylamino (the (1-4C)alkyl group being optionally substituted by (1-4C)alkoxycarbonyl or by carboxy), benzyloxy-(1-4C)alkyl or (1-10C)alkyl {optionally substituted as defined for (Rc2c)};
(Rc2e) R15O- wherein R15 is benzyl, (1-6C)alkyl {optionally substituted as defined for (Rc2c)}, CY1, CY2 or AR2b;

(Rc3) hydrogen, cyano, 2-cyanoethenyl, 2-cyano-2-((1-4C)alkyl)ethenyl, 2-((1-4C)alkylaminocarbonyl)ethenyl, 2-((1-4C)alkoxycarbonyl)ethenyl, 2-nitroethenyl, 2-nitro-2-((1-4C)alkyl)ethenyl, 2-(AR1)ethenyl, 2-(AR2)ethenyl, or of the formula (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 (1-4C)alkyl, phenyl or AR2 (when X00 is -OR17, -SR17 and -NHR17); and R16 is cyano, nitro, (1-4C)alkylsulfonyl, (4-7C)cycloalkylsulfonyl, phenylsulfonyl, (1-4C)alkanoyl and (1-4C)alkoxycarbonyl;

(Rc4) trityl, AR1, AR2, AR2a, AR2b, AR3, AR3a, AR3b;
(Rc5) RdOC(Re)=CH(C=O)-, RfC(=O)C(=O)-, RgN=C(Rh)C(=O)- or RiNHC(Rj)=CHC(=O)- wherein Rd is (1-6C)alkyl; Re is hydrogen or (1-6C)alkyl, or Rd and Re together form a (3-4C)alkylene chain; Rf is hydrogen, (1-6C)alkyl, hydroxy(1-6C)alkyl, (1-6C)alkoxy(1-6C)alkyl, -NRvRw [wherein Rv is hydrogen or (1-4C)alkyl; Rw is hydrogen or (1-4C)alkyl], (1-6C)alkoxy, (1-6C)alkoxy(1-6C)alkoxy, hydroxy(2-6C)alkoxy, (1-4C)alkylamino(2-6C)alkoxy, di-(1-4C)alkylamino(2-6C)alkoxy; Rg is (1-6C)alkyl, hydroxy or (1-6C)alkoxy; Rh is hydrogen or (1-6C)alkyl; Ri is hydrogen, (1-6C)alkyl, AR1, AR2, AR2a, AR2b and Rj is hydrogen or (1-6C)alkyl;

wherein AR1 is an optionally substituted phenyl or optionally substituted naphthyl;
AR2 is an optionally substituted 5- or 6-membered, fully unsaturated (i.e with the maximum degree of unsaturation) monocyclic heteroaryl ring containing up to four heteroatoms independently selected from O, N and S (but not containing any O-O, O-S or S-S
bonds), and linked via a ring carbon atom, or a ring nitrogen atom if the ring is not thereby quaternised;
AR2a is a partially hydrogenated version of AR2 (i.e. AR2 systems retaining some, but not the full, degree of unsaturation), linked via a ring carbon atom or linked via a ring nitrogen atom if the ring is not thereby quaternised;

AR2b is a fully hydrogenated version of AR2 (i.e. AR2 systems having no unsaturation), linked via a ring carbon atom or linked via a ring nitrogen atom;
AR3 is an optionally substituted 8-, 9- or 10-membered, fully unsaturated (i.e with the maximum degree of unsaturation) bicyclic heteroaryl ring containing up to four heteroatoms independently selected from O, N and S (but not containing any O-O, O-S or S-S
bonds), and linked via a ring carbon atom in either of the rings comprising the bicyclic system;
AR3a is a partially hydrogenated version of AR3 (i.e. AR3 systems retaining some, but not the full, degree of unsaturation), linked via a ring carbon atom, or linked via a ring nitrogen atom if the ring is not thereby quaternised, in either of the rings comprising the bicyclic system;
AR3b is a fully hydrogenated version of AR3 (i.e. AR3 systems having no unsaturation), linked via a ring carbon atom, or linked via a ring nitrogen atom, in either of the rings comprising the bicyclic system;

AR4 is an optionally substituted 13- or 14-membered, fully unsaturated (i.e with the maximum degree of unsaturation) tricyclic heteroaryl ring containing up to four heteroatoms independently selected from O, N and S (but not containing any O-O, O-S or S-S
bonds), and linked via a ring carbon atom in any of the rings comprising the tricyclic system;
AR4a is a partially hydrogenated version of AR4 (i.e. AR4 systems retaining some, but not the full, degree of unsaturation), linked via a ring carbon atom, or linked via a ring nitrogen atom if the ring is not thereby quaternised, in any of the rings comprising the tricyclic system;
CY1 is an optionally substituted cyclobutyl, cyclopentyl or cyclohexyl ring;
CY2 is an optionally substituted cyclopentenyl or cyclohexenyl ring.

2. A compound of the formula (I), or a pharmaceutically-acceptable salt, or an in-vivo-hydrolysable ester thereof, as claimed in claim 1; wherein Q is Q1 wherein R2 and R3 are independently hydrogen or fluoro; and the groups defined in (TCa) to (TCc) are defined by formulae (TC1) to (TC4) :- wherein in (TC1) : >A3-B3- is >C(Rq)-CH(Rr)- and G is -O-, -S-, -SO-, -SO2- or >N(Rc);
wherein in (TC2) : m1 is 0, 1 or 2; >A3-B3- is >C=C(Rr)- or >C(Rq)-CH(Rr)- and G is -O-, -S-, -SO-, -SO2 or >N(Rc);
wherein in (TC3) : m1 is 0, 1 or 2; >A3-B3- is >C(Rq)-CH(Rr)- (other than when Rq and Rr are both together hydrogen) and G is -O-, -S-, -SO-, -SO2 or >N(Rc);
wherein in (TC4) : n1 is 1 or 2; o1 is 1 or 2 and n1 + ol = 2 or 3; >A3-B3- is >C=C(Rr)- or >C(Rq)-CH(Rr)- or >N-CH2 and G is -O-, -S-, -SO-, -SO2 or >N(Rc); Rp is hydrogen, (1-4C)alkyl (other than when such substitution is defined by >A3-B3-), hydroxy, (1-4C)alkoxy or (1-4C)alkanoyloxy;
wherein in (TC1), (TC2) and (TC4); m1, n1 and o1 are as defined hereinbefore:

>A3-B3- is >N-CH2- and G is >C(R11)(R12), >C=O, >C-OH, >C-(1-4C)alkoxy, >C=N-OH, >C=N-(1-4C)alkoxy, >C=N-NH-(1-4C)alkyl, >C=N-N((1-4C)alkyl)2 (the last two (1-4C)alkyl groups above in G being optionally substituted by hydroxy) or >C=N-N-CO-(1-4C)alkoxy; wherein > represents two single bonds;
Rq is hydrogen, hydroxy, halo, (1-4C)alkyl or (1-4C)alkanoyloxy;
Rr is (independently where appropriate) hydrogen or (1-4C)alkyl;
R11 is hydrogen, (1-4C)alkyl, fluoro(1-4C)alkyl, (1-4C)alkyl-thio-(1-4C)alkyl or hydroxy-(1-4C)alkyl and R12 is -[C(Rr)(Rr)]m2-N(Rr)(Rc) wherein m2 is 0, 1 or 2;
and, other than the ring substitution defined by G, >A3-B3- and Rp, each ring system may be optionally further substituted on a carbon atom not adjacent to the link at >A3- by up to two substituents independently selected from (1-4C)alkyl, fluoro(1-4C)alkyl (including trifluoromethyl), (1-4C)alkyl-thio-(1-4C)alkyl, hydroxy-(1-4C)alkyl, amino, amino-(1-4C)alkyl, (1-4C)alkanoylamino, (1-4C)alkanoylamino-(1-4C)alkyl, carboxy, (1-4C)alkoxycarbonyl, AR-oxymethyl, AR-thiomethyl, oxo (=O) (other than when G is >N-Rc and Rc is group (Rc2) defined hereinbefore) 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 phenyl(1-4C)alkyl, optionally substituted naphthyl, optionally substituted 5- or 6-membered heteroaryl;
an optionally substituted 5/6 or 6/6 bicyclic heteroaryl ring system, in which the bicyclic heteroaryl ring systems may be linked via an atom in either of the rings comprising the bicyclic system, and wherein both the mono- and bicyclic heteroaryl ring systems are linked via a ring carbon atom and may be (partially) hydrogenated; and Rc is selected from groups (Rc1) to (Rc5) defined in claim 1.
3. A compound of the formula (I), or a pharmaceutically-acceptable salt, or an in-vivo-hydrolysable ester thereof, as claimed in claims 1 and 2, in which the optional substituents in AR are independently selected from halo, (1-4C)alkyl , hydroxy, nitro, carbamoyl, (1-4C)alkylcarbamoyl, di-((1-4C)alkyl)carbamoyl, cyano, trifluoromethyl, trifluoromethoxy, amino, (1-4C)alkylamino, di((1-4C)alkyl)amino, (1-4C)alkyl S(O)q (q is 0, 1 or 2), carboxy, (1-4C)alkoxycarbonyl, (2-4C)alkenyl, (2-4C)alkynyl, (1-4C)alkanoyl, (1-4C)alkoxy, (1-4C)alkylS(O)2amino, (1-4C)alkanoylamino, benzoylamino, benzoyl, phenyl (optionally substituted by up to three substituents selected from halo, (1-4C)alkoxy or cyano), furan, pyrrole, pyrazole, imidazole, triazole, pyrimidine, pyridazine, pyridine, isoxazole, oxazole, isothiazole, thiazole, thiophene, hydroxyimino(1-4C)alkyl, (1-4C)alkoxyimino(1-4C)alkyl, hydroxy-(1-4C)alkyl, halo-(1-4C)alkyl, nitro(1-4C)alkyl, amino(1-4C)alkyl, cyano(1-4C)alkyl, (1-4C)alkanesulfonamido, aminosulfonyl, (1-4C)alkylaminosulfonyl and di-((1-4C)alkyl)aminosulfonyl.
4. A compound of the formula (I), or a pharmaceutically-acceptable salt, or an in-vivo-hydrolysable ester thereof, as claimed in any of claims 1-3, and the groups defined in (TCa) to (TCc), and (TC1) to (TC4) are defined by formulae (TC5) to (TC11):- Rc is as defined in claim 1.
5. A compound of the formula (IC), or a pharmaceutically-acceptable salt, or an in-vivo-hydrolysable ester thereof, as claimed in any of claims 1-4, wherein HET is as claimed in any of claims 1-4; R2 and R3 are independently hydrogen or fluoro; Rp1 and Rp2 are independently hydrogen, AR-oxymethyl or AR-thiomethyl [wherein AR is phenyl, phenyl-(1-4C)alkyl, naphthyl, furan, pyrrole, pyrazole, imidazole, triazole, pyrimidine, pyridazine, pyridine, isoxazole, oxazole, isothiazole, thiazole or thiophene], (1-4C)alkyl, carboxy, (1-4C)alkoxycarbonyl, hydroxymethyl, (1-4C)alkoxymethyl or carbamoyl and Rcp is cyano, pyrimidin-2-yl, 2-cyanoethenyl, 2-cyano-2-((1-4C)alkyl)ethenyl or Rcp is of the formula R10p CO-, R10p SO2- or R10p CS- {wherein R10p is hydrogen, (1-5C)alkyl [optionally substituted by one or more groups each independently selected from hydroxy and amino, or optionally monosubstituted by (1-4C)alkoxy, (1-4C)alkylS(O)q-, (1-4C)alkylamino, (1-4C)alkanoyl, naphthoxy, (2-6C)alkanoylamino or (1-4C)alkylS(O)p NH- wherein p is 1 or 2 and q is 0, 1 or 2], imidazole, triazole, pyrimidine, pyridazine, pyridine, isoxazole, oxazole, isothiazole, thiazole, pyridoimidazole, pyrimidoimidazole, quinoxaline, quinazoline, phthalazine, cinnoline or naphthyridine, or R10p is of the formula R10p C(O)O(1-6C)alkyl wherein R11p is (1-6C)alkyl}, or Rcp is of the formula RfC(=O)C(=O)- wherein Rf is (1-6C)alkoxy.
6. A compound of the formula (IC), or a pharmaceutically-acceptable salt, or an in-vivo-hydrolysable ester thereof, as claimed in any of claims 1-5, wherein HET is triazole or tetrazole.
7. A compound, as claimed in any of claims 1-6, being ((5R)-3-(4-(1-(2-Hydroxyacetyl)-1,2,5,6-tetrahydropyridin-4-yl)-3,5-difluorophenyl)-5-(1,2,3-triazol-1-ylmethyl)oxazolidin-2-one;
(5R)-3-(4-(1-((2S)-2,3-Dihydroxypropionyl)-1,2,5,6-tetrahydropyridin-4-yl)-3,5-difluoro-phenyl)-5-(1,2,3-triazol-1-ylmethyl)oxazolidin-2-one;
(5R)-3-(4-(1-(2-Hydroxyacetyl)-1,2,5,6-tetrahydropyridin-4-yl)-3-fluorophenyl)-5-(1,2,3-triazol-1-ylinethyl)oxazolidin-2-one;
(5R)-3-(4-(1-((2S)-2,3-Dihydroxypropionyl)-1,2,5,6-tetrahydropyridin-4-yl)-3-fluorophenyl)-5-(1,2,3-triazol-1-ylmethyl)oxazolidin-2-one; or a pharmaceutically-acceptable salt, or an in-vivo-hydrolysable ester thereof.
8. A compound, as claimed in claim 1, being (5R)-3-(3,5-Difluoro-4-(3,6-dihydro-1,1-dioxo-2H-thiopyran-4-yl)phenyl)-5-(1,2,3-triazol-1-ylmethyl)oxazolidin-2-one.
9. A process for the preparation of a compound of the formula (I) as claimed in claim 1, or pharmaceutically-acceptable salts or in vivo hydrolysable esters thereof, which comprises of (a) to (d):-(a) modification of a substituent in or introduction of a substituent into another compound of formula (I);
(b) reaction of a compound of formula (II):

wherein Y is a displaceable group (which may be preformed, such as chloro or mesylate, or generated in-situ, for example under Mitsunobu conditions) with a compound of the formula (III):

HET

(III) wherein HET is HET-H free-base form or HET- anion formed from the free base form; or (c) by reaction of 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) for HET as 1,2,3-triazole by cycloaddition via the azide (wherein Y in (II) is azide);
and thereafter if necessary: (i) removing any protecting groups; (ii) forming a pharmaceutically-acceptable salt; (iii) forming an in-vivo hydrolysable ester.
10. A method for producing an antibacterial effect in a warm blooded animal which comprises administering to said animal an effective amount of a compound of the formula (I) as claimed in any one of claims 1 to 8, or a pharmaceutically-acceptable salt, or in-vivo hydrolysable ester thereof.
11. A compound of the formula (I) as claimed in any one of claims 1 to 8, or a pharmaceutically-acceptable salt, or in-vivo hydrolysable ester thereof, for use as a medicament.
12. The use of a compound of the formula (I) as claimed in any one of claims 1 to 8, 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.
13. A pharmaceutical composition which comprises a compound of the formula (I) as claimed in any one of claims 1 to 8, or a pharmaceutically-acceptable salt or an in-vivo hydrolysable ester thereof, and a pharmaceutically-acceptable diluent or carrier.
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