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  Substituted isoxazolines and their use as antibacterial agentsUSPTO Application #: 20070281916Title: Substituted isoxazolines and their use as antibacterial agents Abstract: 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.
wherein R13 is, for example, optionally substituted (1-10C)alkyl or R14C(O)O(1-6C)alkyl
wherein Rc is, for example, R13CO—, R13SO2— or R13CS—;
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):
R2 and R3 are independently hydrogen or fluoro;
Q is selected from, for example, Q1 and Q2:
wherein, for example, X is O, S or NH; HET is an optionally substituted C-linked 5-membered heteroaryl ring containing 2 to 4 heteroatoms independently selected from N, O and S;
Compounds of the formula (I), or a pharmaceutically-acceptable salt, or an in-vivo-hydrolysable ester thereof, (end of abstract)
Agent: Astrazeneca R&d Boston - Waltham, MA, US Inventors: Michael Barry Gravestock, Michael John Betts USPTO Applicaton #: 20070281916 - Class: 514210200 (USPTO) Related Patent Categories: Drug, Bio-affecting And Body Treating Compositions, Designated Organic Active Ingredient Containing (doai), Heterocyclic Carbon Compounds Containing A Hetero Ring Having Chalcogen (i.e., O,s,se Or Te) Or Nitrogen As The Only Ring Hetero Atoms Doai, Hetero Ring Is Four-membered And Includes At Least One Ring Nitrogen, Additional Hetero Ring Attached Directly Or Indirectly To The Four-membered Hetero Ring By Nonionic Bonding, The Additional Hetero Ring Contains Ring Nitrogen The Patent Description & Claims data below is from USPTO Patent Application 20070281916. Brief Patent Description - Full Patent Description - Patent Application Claims
[0001] The present invention relates to antibiotic compounds and in particular to antibiotic compounds containing a substituted isoxazoline ring. This invention further relates to processes for their preparation, to intermediates useful in their preparation, to their use as therapeutic agents and to pharmaceutical compositions containing them. [0002] The international microbiological community continues to express serious concern that the evolution of antibiotic resistance could result in strains against which currently available antibacterial agents will be ineffective. In general, bacterial pathogens may be classified as either Gram-positive or Gram-negative pathogens. Antibiotic compounds with effective activity against both Gram-positive and Gram-negative pathogens are generally regarded as having a broad spectrum of activity. The compounds of the present invention are regarded primarily as effective against Gram-positive pathogens because of their particularly good activity against such pathogens. [0003] Gram-positive pathogens, for example Staphylococci, Enterococci, Streptococci and mycobacteria, are particularly important because of the development of resistant strains which are both difficult to treat and difficult to eradicate from the hospital environment once established. Examples of such strains are methicillin resistant staphylococcus (MRSA), methicillin resistant coagulase negative staphylococci (MRCNS), penicillin resistant Streptococcus pneumoniae and multiply resistant Enterococcus faecium. [0004] The major clinically effective antibiotic for treatment of such resistant Gram-positive pathogens is vancomycin. Vancomycin is a glycopeptide and is associated with nephrotoxicity and ototoxicity. Furthermore, and most importantly, antibacterial resistance to vancomycin and other glycopeptides is also appearing. This resistance is increasing at a steady rate rendering these agents less and less effective in the treatment of Gram-positive pathogens. [0005] Certain antibacterial compounds containing an oxazolidinone ring have been described in the art (for example, 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 sidechain may be subject to mammalian peptidase metabolism. [0006] Furthermore, bacterial resistance to known antibacterial agents may develop, for example, by (i) the evolution of active binding sites in the bacteria rendering a previously active pharmacophore less effective or redundant, and/or (ii) the evolution of means to chemically deactivate a given pharmacophore. Therefore, there remains an ongoing need to find new antibacterial agents with a favourable pharmacological profile, in particular for compounds containing new pharmacophores. [0007] We have discovered a class of antibiotic compounds containing a new class of substituted isoxazoline (4,5-dihydro-isoxazole) ring which has useful activity against Gram-positive pathogens including MRSA and MRCNS and, in particular, against various strains exhibiting resistance to vancomycin and against E. faecium strains resistant to both aminoglycosides and clinically used .beta.-lactams. [0008] Accordingly the present invention provides a compound of the formula (I), or a pharmaceutically-acceptable salt, or an in-vivo-hydrolysable ester thereof, wherein [0009] X is O, NH, S, SO or SO.sub.2; [0010] HET is a C-linked 5-membered heteroaryl ring containing 2 to 4 heteroatoms independently selected from N, O and S, which ring is optionally substituted on an available carbon atom by 1 or 2 substituents independently selected from (1-4C)alkyl, amino, (1-4C)alkylamino, (1-4C)alkoxy, (1-4C)alkoxycarbonyl and halogen, and/or on an available nitrogen atom (provided that the ring is not thereby quaternised) by (1-4C)alkyl; or [0011] HET is a C-linked 6-membered heteroaryl ring containing 2 or 3 nitrogen heteroatoms, which ring is optionally substituted on any available C atom by 1, 2 or 3 substituents independently selected from (1-4C)alkyl, amino, (1-4C)alkylamino, (1-4C)alkoxy, (1-4C)alkoxycarbonyl and halogen; [0012] Q is selected from Q1 to Q9:- [0013] wherein R.sup.2 and R.sup.3 are independently hydrogen or fluoro; [0014] wherein A.sub.1 is carbon or nitrogen; B.sub.1 is O or S (or, in Q9 only, NH); X.sub.q is O, S or N--R.sup.1 (wherein R.sup.1 is hydrogen, (1-4C)alkyl or hydroxy-(1-4C)alkyl); and wherein in Q7 each A.sub.1 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 A.sub.1 atoms (when A.sub.1 is carbon), and linked in the 5-membered ring via the specified carbon atom, or via A.sub.1 when A.sub.1 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; [0015] wherein T is selected from the groups in (TA) to (TD) below (wherein AR1, AR2, AR2a, AR2b, AR3, AR3a, AR3b, AR4, AR4a, CY1 and CY2 are defined hereinbelow); [0016] (TA) T is selected from the following groups:- [0017] (TAa) AR1, AR1-(1-4C)alkyl-, AR2 (carbon linked), AR3; [0018] (TAb) AR1-CH(OH), AR2-CH(OH)--, AR3-CH(OH)--; [0019] (TAc) AR1-CO--, AR2-CO--, AR3-CO--, AR4-CO--; [0020] (TAd) AR1-O--, AR2-O--, AR3-O--; [0021] (TAe) AR1-S(O).sub.q--, AR2-S(O).sub.q--, AR3-S(O).sub.q-- (q is 0, 1 or 2); [0022] (TAf) an optionally substituted N-linked (fully unsaturated) 5-membered heteroaryl ring system containing 1, 2 or 3 nitrogen atoms; [0023] (TAg) a carbon linked tropol-3-one or tropol-4-one, optionally substituted in a position not adjacent to the linking position; or [0024] (TB) T is selected from the following groups:- [0025] (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)alkylS(O).sub.q-- (q is 0, 1 or 2), CY1, CY2 or AR1}; [0026] (TBb) --NRv.sup.1Rw.sup.1; [0027] (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; [0028] (TBd) R.sup.10CO--, R.sup.10S(O).sub.q-- (q is 0, 1 or 2) or R.sup.10CS-- [0029] wherein R.sup.10 is selected from the following groups:- [0030] (TBda) CY1 or CY2; [0031] (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 [0032] (TBdc) (1-4C)alkyl {optionally substituted as defined in (TBa) above, or by (1-4C)alkylS(O).sub.pNH-- or (1-4C)alkylS(O).sub.p-((1-4C)alkyl)N-- (p is 1 or 2)}; [0033] wherein Rv is hydrogen or (1-4C)alkyl; Rw is hydrogen or (1-4C)alkyl; Rv.sup.1 is hydrogen, (1-4C)alkyl or (3-8C)cycloalkyl; Rw.sup.1 is hydrogen, (1-4C)alkyl, (3-8C)cycloalkyl, (1-4C)alkyl-CO-- or (1-4C)alkylS(O).sub.q-- (q is 1 or 2); or [0034] (TC) T is selected from the following groups:- [0035] (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 sp.sup.3 carbon atom; [0036] (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 sp.sup.3 or sp.sup.2 carbon atom, which monocyclic ring is fully saturated other than (where appropriate) at a linking sp.sup.2 carbon atom; [0037] (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 sp.sup.3 or sp.sup.2 carbon atom, which monocyclic ring is fully saturated other than (where appropriate) at a linking sp.sup.2 carbon atom; or [0038] (TD) T is selected from the following groups:- [0039] (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 sp.sup.3 or sp.sup.2 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 [0040] (i) fully saturated other than (where appropriate) at a linking sp.sup.2 carbon atom; [0041] (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 sp.sup.2 carbon atom) or one --N(Rc)-group in an optional substituent (not adjacent to the linking position) and is [0042] (iii) optionally further substituted on an available ring carbon atom; or [0043] (TDb) a 7-, 8- or 9-membered bicyclic ring system (linked via a ring nitrogen atom or a ring sp.sup.3 or sp.sup.2 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 [0044] (i) fully saturated other than (where appropriate) at a linking sp.sup.2 carbon atom; [0045] (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 sp.sup.2 carbon atom) or one --N(Rc)-group in an optional substituent (not adjacent to the linking position) and is [0046] (iii) optionally further substituted on an available ring carbon atom; [0047] wherein Rc is selected from groups (Rc1) to (Rc5):- [0048] (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).sub.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)alkoxycarbonylamino, N-(1-4C)alkyl-N-(1-6C)alkanoylamino, (1-4C)alkylS(O).sub.pNH-- or (1-4C)alkylS(O).sub.p-((1-4C)alkyl)N-- (p is 1 or 2)}; [0049] (Rc2) R.sup.13CO--, R.sup.13SO.sub.2-- or R.sup.13CS-- [0050] wherein R.sup.13 is selected from (Rc2a) to (Rc2e):- [0051] (Rc2a) AR1, AR2, AR2a, AR2b, AR3, AR3a, AR3b, AR4, AR4a, CY1, CY2; [0052] (Rc2b) hydrogen, (1-4C)alkoxycarbonyl, trifluoromethyl, --NRvRw [wherein Rv is hydrogen or (1-4C)alkyl; Rw is hydrogen or (1-4C)alkyl], 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, 2-(AR2a)ethenyl; [0053] (Rc2c) (1-10C)alkyl {optionally substituted by one or more groups (including geminal disubstitution) each independently selected from hydroxy, (1-10C)alkoxy, (1-4C)alkoxy-(1-4C)alkoxy, (1-4C)alkoxy-(1-4C)alkoxy-(1-4C)alkoxy, (1-4C)alkanoyl, phosphoryl [--O--P(O)(OH).sub.2, and mono- and di-(1-4C)alkoxy derivatives thereof], phosphiryl [--O--P(OH).sub.2 and mono- and di-(1-4C)alkoxy derivatives thereof], phosphiryl [--O--P(OH).sub.2and mono- and d-(1- 4C)alkoxy derivatives thereof], and amino; and/or optionally substituted by one group selected from phosphonate [phosphono, --P(O)(OH).sub.2, and mono- and di-(1-4C)alkoxy derivatives thereof], phosphinate [--P(OH).sub.2 and mono- and di-(1-4C)alkoxy derivatives thereof], cyano, halo, trifluoromethyl, (1-4C)alkoxycarbonyl, (1-4C)alkoxy-(1-4C)alkoxycarbonyl, (1-4C)alkoxy-(1-4C)alkoxy-(1-4C)alkoxycarbonyl, (1-4C)alkylamino, di((1-4C)alkyl)amino, (1-6C)alkanoylamino, (1-4C)alkoxycarbonylamino, N-(1-4C)alkyl-N-(1-6C)alkanoylamino, (1-4C)alkylaminocarbonyl, di((1-4C)alkyl)aminocarbonyl, (1-4C)alkylS(O).sub.pNH--, (1-4C)alkylS(O).sub.p-((1-4C)alkyl)N--, fluoro(1-4C)alkylS(O).sub.pNH--, fluoro(1-4C)alkylS(O).sub.p((1-4C)alkyl)N--, (1-4C)alkylS(O).sub.q-- [the (1-4C)alkyl group of (1-4C)alkylS(O).sub.q-- being optionally substituted by one substituent selected from hydroxy, (1-4C)alkoxy, (1-4C)alkanoyl, phosphoryl [--O--P(O)(OH).sub.2, and mono- and di-(1-4C)alkoxy derivatives thereof], phosphiryl [--O--P(OH).sub.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)alkoxycarbonyl, carboxy, (1-4C)alkylamino, di((1-4C)alkyl)amino, (1-6C)alkanoylamino, (1-4C)alkoxycarbonylamino, N-(1-4C)alkyl-N-(1-6C)alkanoylamino, (1-4C)alkylaminocarbonyl, di((1-4C)alkyl)aminocarbonyl, (1-4C)alkylS(O).sub.pN--, (1-4C)alkylS(O).sub.p-((1-4C)alkyl)N--, (1-4C)alkylS(O).sub.q--, AR1-S(O).sub.q--, AR2-S(O).sub.q--, AR3-S(O).sub.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).sub.q--, AR2-S(O).sub.q--, AR3-S(O).sub.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}; [0054] (Rc2d) R.sup.14C(O)O(1-6C)alkyl wherein R.sup.14 is 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)}; [0055] (Rc2e) R.sup.15O-- wherein R.sup.15 is benzyl, (1-6C)alkyl {optionally substituted as defined for [0056] (Rc2c)}, CY1, CY2 or AR2b; [0057] (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) [0058] wherein X.sup.00 is --OR.sup.17, --SR.sup.17, --NHR.sup.17 and --N(R.sup.17).sub.2; [0059] wherein R.sup.17 is hydrogen (when X.sup.00 is --NHR.sup.17 and --N(R.sup.17).sub.2), and R.sup.17 is (1-4C)alkyl, phenyl or AR2 (when X.sup.00 is --OR.sup.17, --SR.sup.17 and --NHR.sup.17); and R.sup.16 is cyano, nitro, (1-4C)alkylsulfonyl, (4-7C)cycloalkylsulfonyl, phenylsulfonyl, (1-4C)alkanoyl and (1-4C)alkoxycarbonyl; [0060] (Rc4) trityl, AR1, AR2, AR2a, AR2b, AR3, AR3a, AR3b; [0061] (Rc5) RdOC(Re)=CH(C.dbd.O)--, RfC(.dbd.O)C(.dbd.O)--, RgN.dbd.C(Rh)C(.dbd.O)-- or RiNHC(Rj)=CHC(.dbd.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, [0062] AR2b and Rj is hydrogen or (1-6C)alkyl; wherein [0063] AR1 is an optionally substituted phenyl or optionally substituted naphthyl; [0064] 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; [0065] 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; [0066] 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; [0067] 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; [0068] 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; [0069] 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; [0070] 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; [0071] 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; [0072] CY1 is an optionally substituted cyclobutyl, cyclopentyl or cyclohexyl ring; [0073] CY2 is an optionally substituted cyclopentenyl or cyclohexenyl ring. [0074] In this specification, where it is stated that a ring may be linked via an sp.sup.2 carbon atom, which ring is fully saturated other than (where appropriate) at a linking sp.sup.2 carbon atom, it is to be understood that the ring is linked via one of the carbon atoms in a C.dbd.C double bond. [0075] In another embodiment, (Rc1) is as defined above other than the optional phenyl substituent on (1-6C)alkyl is optionally substituted as for AR1 defined hereinafter; and (Rc2c), is as defined above and further includes carboxy as an optional substituent on R.sup.13 as (1-10C)alkyl. [0076] (TAf) When T is an optionally substituted N-linked (fully unsaturated) 5-membered heteroaryl ring system containing 1, 2 or 3 nitrogen atoms, it is preferably selected from a group of formula (TAf1) to (TAf6) below (particularly (TAf1), (TAf2), (TAf4) and (TAf5), and especially (TAf1) and/or (TAf2)). The above preferred values of (TAf) are particularly preferred when present in Q1 or Q2, especially Q1. wherein: [0077] R.sup.6 is selected (independently where appropriate) from hydrogen, (1-4C)alkyl, (1-4C)alkoxycarbonyl, (1-4C)alkanoyl, carbamoyl and cyano; [0078] R.sup.4 and R.sup.5 are independently selected from hydrogen, halo, trifluoromethyl, cyano, nitro, (1-4C)alkoxy, (1-4C)alkylS(O).sub.q-- (q is 0, 1 or 2), (1-4C)alkanoyl, (1-4C)alkoxycarbonyl, (2-4C)alkanoyloxy-(1-4C)alkyl, benzoxy-(1-4C)alkyl, (2-4C)alkanoylamino, --CONRvRw, --NRvRw and (1-4C)alkyl {optionally substituted by hydroxy, trifluoromethyl, cyano, nitro, (1-4C)alkoxy, (1-4C)alkylS(O).sub.q-- (q is 0, 1 or 2), (1-4C)alkoxycarbonyl, (1-4C)alkanoylamino, --CONRvRw, --NRvRw; wherein RvRw is hydrogen or (1-4C)alkyl; Rw is hydrogen or (1-4C)alkyl}; or R.sup.4 is selected from one of the groups in (TAfa) to (TAfc) below, or (where appropriate) one of R.sup.4 and R.sup.5 is selected from the above list of R.sup.4 and R.sup.5 values, and the other is selected from one of the groups in (TAfa) to (TAfc) below:- [0079] (TAfa) a group of the formula (TAfa1) [0080] wherein Z.sup.0 is hydrogen or (1-4C)alkyl; [0081] X.sup.0 and Y.sup.0 are independently selected from hydrogen, (1-4C)alkyl, (1-4C)alkoxycarbonyl, halo, cyano, nitro, (1-4C)alkylS(O).sub.q-- (q is 0, 1 or 2), RvRwNSO.sub.2--, trifluoromethyl, pentafluoroethyl, (1-4C)alkanoyl and --CONRvRw [wherein Rv is hydrogen or (1-4C)alkyl; [0082] Rw is hydrogen or (1-4C)alkyl]; or [0083] one of X.sup.0 and Y.sup.0 is selected from the above list of X.sup.0 and Y.sup.0 values, and the other is selected from phenyl, phenylcarbonyl, --S(O).sub.q-phenyl (q is 0, 1 or 2), N-(phenyl)carbamoyl, phenylaminosulfonyl, AR2, (AR2)-CO--, (AR2)-S(O).sub.q-- (q is 0, 1 or 2), N-(AR2)carbamoyl and (AR2)aminosulfonyl; wherein any phenyl group in (TAfa) may be optionally substituted by up to three substituents independently selected from (1-4C)alkyl, cyano, trifluoromethyl, nitro, halo and (1-4C)alkylsulfonyl; [0084] (TAjb) an acetylene of the formula --.ident.--H or --.ident.-(1-4C)alkyl; [0085] (TAfc) --X.sup.1--Y.sup.1-AR2, --X.sup.1--Y.sup.1-AR2a, --X.sup.1--Y.sup.1-AR2b, --X.sup.1--Y-AR3, --X.sup.1-AR3a or --X.sup.1--Y.sup.1-AR3b; [0086] wherein X.sup.1 is a direct bond or --CH(OH)-- and [0087] Y.sup.1 is --(CH.sub.2).sub.m--, --(CH.sub.2).sub.n--NH--(CH.sub.2).sub.m, --CO--(CH.sub.2).sub.m--, --CONH--(CH.sub.2).sub.m--, --C(.dbd.S)NH--(CH.sub.2).sub.m-- or --C(.dbd.O)O--(CH.sub.2).sub.m--; [0088] or wherein X.sup.1 is --(CH.sub.2).sub.n-- or --CH(Me)-(CH.sub.2).sub.m-- and [0089] Y.sup.1 is --(CH.sub.2).sub.m--NH--(CH.sub.2).sub.m--, --CO--(CH.sub.2).sub.m--, --CONH--(CH.sub.2).sub.m--, --C(.dbd.S)NH--(CH.sub.2).sub.m--, --C(.dbd.O)O--(CH.sub.2).sub.m-- or --S(O).sub.q--(CH.sub.2).sub.m--; [0090] or wherein X.sup.1 is --CH.sub.2O--, --CH.sub.2NH-- or --CH.sub.2N((1-4C)alkyl)- and [0091] Y.sup.1 is --CO--(CH.sub.2).sub.m--, --CONH--(CH.sub.2).sub.m-- or --C(.dbd.S)NH--(CH.sub.2).sub.m--; and additionally Y.sup.1 is --SO.sub.2-- when X.sup.1 is --CH.sub.2NH-- or --CH.sub.2N((1-4C)alkyl)-, and Y.sup.1 is --(CH.sub.2).sub.m-- when X.sup.1 is --CH.sub.2O-- or -- CH.sub.2N((1-4C)alkyl)-; wherein n is 1, 2 or 3; m is 0, 1, 2 or 3 and q is 0, 1 or 2; and when Y.sup.1 is --(CH.sub.2).sub.m--NH--(CH.sub.2).sub.m-- each m is independently selected from 0, 1, 2 or 3. [0092] It is to be understood that when a value for --X.sup.1-- is a two-atom link and is written, for example, as --CH.sub.2NH-- it is the left hand part (--CH.sub.2-- here) which is bonded to the group of formula (TAf1) to (TAf6) and the right hand part (--NH-- here) which is bonded to --Y.sup.1-- in the definition in (TAfc). Similarly, when --Y.sup.1-- is a two-atom link and is written, for example, as --CONH-- it is the left hand part of --Y.sup.1-- (--CO-- here) which is bonded to the right hand part of --X.sup.1--, and the right hand part of --Y-- (--NH-- here) which is bonded to the AR2, AR2a, AR2b, AR3, AR3a or AR3b moiety in the definition in (TAfc). [0093] Preferably R.sup.6 is hydrogen or (1-4C)alkyl, and R.sup.4 and R.sup.5 are independently selected from hydrogen, (1-4C)alkyl or one of R.sup.4 and R.sup.5 is selected from group (TAfa). Other preferable substituents on the (TAf1) to (TAf6) are illustrated in the accompanying Examples. Most preferable is (TAf2) with such preferable substituents. [0094] (TAg) When T is a carbon linked tropol-3-one or tropol-4-one, optionally substituted in a position not adjacent to the linking position (TAg), it is preferably selected from a group of formula (TAg1), (TAg2) or (TAg3). The above preferred values of (TAg) are particularly preferred when present in Q1 or Q2, especially Q1. wherein R.sup.7 is selected from [0095] (TAga) hydrogen, (1-4C)alkyl {optionally substituted by one or two substituents (excluding geminal disubstitution) independently selected from fluoro, hydroxy, (1-4C)alkoxy and --NRvRw]}; or [0096] (TAgb) R.sup.8--O--, R.sup.8--S--, R.sup.8--NH-- or R.sup.8R.sup.8--N--; [0097] wherein R.sup.8 is selected (independently where appropriate) from hydrogen, (1-4C)alkyl or (3-8C)cycloalkyl {both optionally substituted by one or two substituents (excluding geminal disubstitution) independently selected from hydroxy, (1-4C)alkoxy, (1-4C)alkoxycarbonyl and --NRvRw}, (2-4C)alkenyl {optionally substituted by one or two --NRvRw substituents}, (1-4C)alkanoyl {optionally substituted by one or two substituents independently selected from --NRvRw and hydroxy}, phenyl-(1-4C)alkyl or pyridyl-(1-4C)alkyl {the phenyl and pyridyl (preferably pyridin-4-yl) rings being optionally substituted by one or two --NRvRw substituents}; or [0098] (TAgc) morpholino, thiomorpholino, pyrrolidino {optionally independently substituted in the 3- and/or 4-positions by (1-4C)alkyl}, piperidino substituted in the 4-position by R.sup.9--, R.sup.9--O--, R.sup.9--S--, R.sup.9--NH-- or R.sup.9R.sup.9--N--; wherein R.sup.9 is selected (independently where appropriate) from hydrogen, (1-4C)alkyl {optionally substituted by one or two (excluding geminal disubstitution) hydroxy, (1-4C)alkoxy, (1-4C)alkoxycarbonyl or --NRvRw} and piperazino {optionally substituted in the 4-position by (1-4C)alkyl, (3-8C)cycloalkyl, (1-4C)alkanoyl, (1-4C)alkoxycarbonyl or (1-4C)alkylsulfonyl, and optionally independently substituted in the 3- and/or 5-positions by (1-4C)alkyl}; wherein Rv is hydrogen or (1-4C)alkyl; Rw is hydrogen or (1-4C)alkyl. [0099] (TC) Preferred values for the optional substituents and groups defined in (TCa) to (TCc) are defined by formulae (TC1) to (TC4):- [0100] wherein in (TC1): >A.sub.3-B.sub.3-- is >C(Rq)-CH(Rr)- and G is --O--, --S--, --SO--, --SO.sub.2-- or >N(Rc); [0101] wherein in (TC2): m1 is 0, 1 or 2; >A.sub.3-B.sub.3-- is >C.dbd.C(Rr)- or >C(Rq)-CH(Rr)- and G is --O--, --S--, --SO--, --SO.sub.2-- or >N(Rc); [0102] wherein in (TC3): m1 is 0, 1 or 2; >A.sub.3-B.sub.3-- is >C(Rq)-CH(Rr)- (other than when Rq and Rr are both together hydrogen) and G is --O--, --S--, --SO--, --SO.sub.2-- or >N(Rc); [0103] wherein in (TC4): n1 is 1 or 2; o1 is 1 or 2 and n1+o1=2 or 3; >A.sub.3-B.sub.3-- is >C.dbd.C(Rr)- or >C(Rq)-CH(Rr)- or >N--CH.sub.2-- and G is --O--, --S--, --SO--, --SO.sub.2-- or >N(Rc); Rp is hydrogen, (1-4C)alkyl (other than when such substitution is defined by >A.sub.3-B.sub.3--), hydroxy, (1-4C)alkoxy or (1-4C)alkanoyloxy; [0104] wherein in (TC1), (TC2) and (TC4); m1, n1 and o1 are as defined hereinbefore: [0105] >A.sub.3-B.sub.3-- is >N--CH.sub.2-- and G is >C(R.sup.11)(R.sup.12), >C.dbd.O, >C--OH, >C-(1-4C)alkoxy, >C.dbd.N--OH, >C.dbd.N-(1-4C)alkoxy, >C.dbd.N--NH-(1-4C)alkyl, >C.dbd.N--N((1-4C)alkyl).sub.2 (the last two (1-4C)alkyl groups above in G being optionally substituted by hydroxy) or >C.dbd.N--N--CO-(1-4C)alkoxy; wherein >represents two single bonds; [0106] Rq is hydrogen, hydroxy, halo, (1-4C)alkyl or (1-4C)alkanoyloxy; [0107] Rr is (independently where appropriate) hydrogen or (1-4C)alkyl; [0108] R.sup.11 is hydrogen, (1-4C)alkyl, fluoro(1-4C)alkyl, (1-4C)alkyl-thio-(1-4C)alkyl or hydroxy-(1-4C)alkyl and R.sup.12 is --[C(Rr)(Rr)].sub.m2-N(Rr)(Rc) wherein m2 is 0, 1 or 2; [0109] and, other than the ring substitution defined by G, >A.sub.3-B.sub.3-- and Rp, each ring system may be optionally further substituted on a carbon atom not adjacent to the link at >A.sub.3- 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 (.dbd.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--); [0110] wherein AR (or ARp) is as defined for formula (IP) hereinafter; Rc is selected from groups (Rc1) to (Rc5) defined hereinbefore. [0111] For the avoidance of doubt, ( ).sub.m1, ( ).sub.n1 and ( ).sub.o1 indicate (--CH.sub.2--).sub.m1, (--CH.sub.2--).sub.n1 and (--CH.sub.2--).sub.o1 respectively (optionally substituted as described above). [0112] In the above definition of (TC1) to (TC4) and of the further optional substituents, AR is preferably AR2, and the further optional substituents are preferably not selected from the values listed for Rc. A preferred value for G is >N(Rc) or >C(R.sup.11)(R.sup.12). Also preferred is G as O or S, particularly in (TC4) when Rp is hydrogen. Preferred is (TC4) as piperazinyl, morpholino or thiomorpholino or as tetrahydropyridin-4-yl. [0113] Particularly preferred values for the optional substituents and groups defined in (TCa) to (TCc), and (TC1) to (TC4) are contained in the following definitions (TC5) to (TC11):- wherein Rc has any of the values listed hereinbefore or hereinafter. [0114] Especially preferred are (TC5), (TC6), (TC7) and (TC9), most especially (TC5) in which Rc has any of the values listed hereinbefore or hereinafter (especially R.sup.13CO-- with the preferable R.sup.13 values given hereinafter). In (TC5) Rc is preferably selected from the group (Rc2), especially R.sup.13CO-- with the preferable R.sup.13 values given hereinafter. In (TC7) Rc is preferably selected from group (Rc3) or (Rc4). [0115] The above preferred values of (TCa) to (TCc) are particularly preferred when present in Q1 or Q2, especially Q1 (especially when HET is isoxazole). X as O or NH is particularly preferred. [0116] (TDa) When T is a bicyclic spiro-ring system as defined in (TDa), it is preferably selected from a group of formula (TDa1) to (TDa9). The above preferred values of (TDa) are particularly preferred when present in Q1 or Q2, especially Q1. wherein; [0117] (i) the A.sub.4 linking group is a nitrogen atom or an sp.sup.3 or sp.sup.2 carbon atom (with the double bond, where appropriate, orientated in either direction); and [0118] (ii) one of the ring carbon atoms at positions marked * and ** is replaced by one of the following groups --NRc-, >CH--NHRc, >CH--NRc-(1-4C)alkyl, >CH--CH.sub.2--NHRc, >CH--CH.sub.2--NRc-(1-4C)alkyl [wherein a central --CH.sub.2-- chain link is optionally mono- or di-substituted by (1-4C)alkyl]; with the provisos that positions marked * are not replaced by --NH-- in the ring containing the A.sub.4 link when A.sub.4 is a nitrogen atom or an sp.sup.2 carbon atom, and that positions marked * are not replaced by --NH-- in the three membered ring in (TDa1), (TDa4) and (TDa5); and [0119] (iii) the ring system is optionally (further) substituted on an available ring carbon atom 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, AR2-oxymethyl, AR2-thiomethyl, oxo (.dbd.O) (other than when the ring contains an >N-Rc and Rc is group (Rc2)) and also hydroxy or halo; [0120] wherein Rc has any of the values listed hereinbefore or hereinafter. [0121] (TDb) When T is a 7-, 8- or 9-membered 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 the ring skeletons shown in formulae (TDb1) to (TDb14):- wherein; [0122] (i) the ring system contains 0, 1 or 2 ring nitrogen atoms (and optionally a further O or S ring heteroatom),and when present the ring nitrogen, O or S heteroatom/s are at any position other than as part of the 3-membered ring in (TDb1); [0123] (ii) the ring system is linked via a ring nitrogen atom or a ring sp.sup.3 or sp.sup.2 carbon atom (with the double bond, where appropriate, orientated in either direction) from any position in either ring [other than from a bridgehead position or from an sp.sup.2 carbon atom in the 4-membered ring in (TDb2), (TDb6) and (TDb11)]; [0124] (iii) one of the ring carbon atoms at a position not adjacent to the linking position, is replaced (other than when the ring contains an O or S heteroatom) by one of the following groups --NRc-[not at a bridgehead position], >C(H)--NHRc, >C(H)--NRc-(1-4C)alkyl, >C(H)--CH.sub.2--NHRc, >C(H)--CH.sub.2--NRc-(1-4C)alkyl [wherein the hydrogen atom shown in brackets is not present when the replacement is made at a bridgehead position and wherein a central --CH.sub.2-- chain link is optionally mono- or di-substituted by (1-4C)alkyl]; with the proviso that when the ring system is linked via a ring nitrogen atom or an sp.sup.2 carbon atom any replacement of a ring carbon atom by --NRc-, O or S is at least two carbon atoms away from the linking position; and [0125] (iv) the ring system is optionally (further) substituted on an available ring carbon atom as for the bicyclic spiro-ring systems described in (TDa); wherein Rc has any of the values listed hereinbefore or hereinafter. [0126] It will be appreciated that unstable anti-Bredt compounds are not contemplated in this definition (i.e. compounds with structures (TDb3), (TDb4), (TDb7), (TDb8), (TDb9), (TDb12), (TDb13) and (TDb14) in which an sp.sup.2 carbon atom is directed towards a bridgehead position). [0127] Particularly preferred values of (TDb) are the following structures of formula (TDb4), (TDb8) and/or (TDb9); wherein Rc has any of the values listed hereinbefore or hereinafter. The above preferred values of (TDb) are particularly preferred when present in Q1 or Q2, especially Q1. [0128] In another embodiment there is provided a compound of formula (I) as defined by formula (IP) below: wherein [0129] T.sup.1 is a C-linked isoxazole ring which is optionally substituted on any available C atom by 1 or 2 substituents independently selected from (1-4C)alkyl, amino, (1-4C)alkylamino, (1-4C)alkoxy and halogen; [0130] Q is wherein: [0131] R.sup.2 and R.sup.3 are independently hydrogen or fluoro; [0132] R.sup.6p is hydrogen, (1-4C)alkyl, hydroxy, (1-4C)alkoxy or (2-4C)alkanoyloxy; [0133] >A-B-- is of the formula >C.dbd.C(R.sup.a)--, >CHCHR.sup.a--, >C(OH)CHR.sup.a-- or >N--CH.sub.2-- (>represents two single bonds) wherein R.sup.a is hydrogen or (1-4C)alkyl; [0134] D is O, S, SO, SO.sub.2 or NR.sup.7p; [0135] R.sup.4p and R.sup.5p are independently oxo (.dbd.O) [but not when R.sup.7p is group (PC) below], (1-4C)alkyl, (1-4C)alkanoylamino-(1-4C)alkyl, hydroxy-(1-4C)alkyl, carboxy, (1-4C)alkoxycarbonyl, ARp-oxymethyl, ARp-thiomethyl (wherein ARp is as defined hereinbelow) or independently as defined for R.sup.7p hereinbelow with the proviso that R.sup.4p and R.sup.5p are not phenyl, benzyl, ARp (as defined hereinbelow), a tetrazole ring system, cyclopentyl or cyclohexyl; and when D is O or S, R.sup.4p and R.sup.5p are additionally independently hydroxy or bromo; [0136] wherein R.sup.7p is selected from (PA) to (PE):- [0137] (PA) hydrogen, cyano, 2-((1-4C)alkoxycarbonyl)ethenyl, 2-cyanoethenyl, 2-cyano-2-((1-4C)alkyl)ethenyl, 2-((1-4C)alkylaminocarbonyl)ethenyl; [0138] (PB) phenyl, benzyl, ARp (as defined hereinbelow) or a tetrazole ring system [optionally mono-substituted in the 1- or 2-position of the tetrazole ring by (1-4C)alkyl, (2-4C)alkenyl, (2-4C)alkynyl or (1-4C)alkanoyl] wherein the tetrazole ring system is joined to the nitrogen in NR.sup.7p by a ring carbon atom; [0139] (PC) R.sup.10pCO--, R.sup.10pSO.sub.2-- or R.sup.10pCS-- [0140] wherein R.sup.10p is selected from (PCa) to (PCf):- [0141] (PCa) ARp (as defined hereinbelow); [0142] (PCb) cyclopentyl or cyclohexyl or 1,3-dioxolan-4-yl or 1,4-dioxan-2-yl or 1,3-dioxan-4-yl [optionally mono- or disubstituted by substituents independently selected from (1-4C)alkyl (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), (1-4C)alkoxy, (1-4C)alkylthio, acetamido, (1-4C)alkanoyl, cyano and trifluoromethyl]; [0143] (PCc) hydrogen, (1-4C)alkoxycarbonyl, trifluoromethyl, amino, (1-4C)alkylamino, di((1-4C)alkyl)amino, 2-(5- or 6-membered heteroaryl)ethenyl, 2-(5- or 6-membered (partially) hydrogenated heteroaryl)ethenyl, 2-phenylethenyl [wherein the heteroaryl or phenyl substituent is optionally substituted on an available carbon atom by up to three substituents independently selected from (1-4C)alkoxy, halo, cyano and (for the phenyl substituent only) (1-4C)alkylsulfonyl]; [0144] (PCd) (1-10C)alkyl [optionally substituted by one or more groups (including geminal disubstitution) each independently selected from hydroxy and amino, or optionally monosubstituted by cyano, halo, (1-10C)alkoxy, trifluoromethyl, (1-4C)alkoxy-(1-4C)alkoxy, (1-4C)alkoxy-(1-4C)alkoxy-(1-4C)alkoxy, (1-4C)alkanoyl, (1-4C)alkoxycarbonyl, (1-4C)alkylamino, di((1-4C)alkyl)amino, (1-6C)alkanoylamino, (1-4C)alkoxycarbonylamino, N-(1-4C)alkyl-N-(2-6C)alkanoylamino, (1-4C)alkylS(O).sub.pNH--, (1-4C)alkylS(O).sub.p((1-4C)alkyl)N--, fluoro(1-4C)alkylS(O).sub.pNH--, fluoro(1-4C)alkylS(O).sub.p((1-4C)alkyl)N--, phosphono, (1-4C)alkoxy(hydroxy)phosphoryl, di-(1-4C)alkoxyphosphoryl, (1-4C)alkylS(O).sub.q--, phenyl, naphthyl, phenoxy, naphthoxy, phenylamino, naphthylamino, phenylS(O).sub.q--, naphthylS(O).sub.q-- [wherein said phenyl and naphthyl groups are optionally substituted by up to three substituents independently selected from (1-4C)alkoxy, halo and cyano], or CYp (as defined hereinbelow), wherein (where appropriate) p is 1 or 2 and q is 0, 1 or 2]; [0145] (PCe) R.sup.11pC(O)O(1-6C)alkyl wherein R.sup.11p is an optionally substituted 5- or 6-membered heteroaryl, optionally substituted phenyl, (1-4C)alkylamino, benzyloxy-(1-4C)alkyl or optionally substituted (1-10C)alkyl; [0146] (PCf) R.sup.12pO-- wherein R.sup.12p is benzyl or optionally substituted (1-6C)alkyl; [0147] (PD) R.sup.dOC(R.sup.e).dbd.CH(C.dbd.O)--, R.sup.fC(.dbd.O)C(.dbd.O)--, R.sup.gN.dbd.C(R.sup.h)C(.dbd.O)-- or R.sup.iNHC(R.sup.j).dbd.CHC(.dbd.O)-- wherein R.sup.d is (1-6C)alkyl, R.sup.e is hydrogen or (1-6C)alkyl, or R.sup.d and R.sup.e together form a (3-4C)alkylene chain, R.sup.f is hydrogen, (1-6C)alkyl, hydroxy(1-6C)alkyl, (1-6C)alkoxy(1-6C)alkyl, amino, (1-4C)alkylamino, di-(1-4C)alkylamino, (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, R.sup.g is (1-6C)alkyl, hydroxy or (1-6C)alkoxy, R.sup.h is hydrogen or (1-6C)alkyl, R.sup.i is hydrogen, (1-6C)alkyl, optionally substituted phenyl or an optionally substituted 5- or 6-membered heteroaryl [and (partially) hydrogenated versions thereof] and R.sup.i is hydrogen or (1-6C)alkyl; [0148] (PE) R.sup.14pCH(R.sup.13p)(CH.sub.2).sub.m-- wherein m is 0 or 1, R.sup.13p is fluoro, cyano, (1-4C)alkoxy, (1-4C)alkylsulfonyl, (1-4C)alkoxycarbonyl or hydroxy, (provided that when m is 0, R.sup.13p is not fluoro or hydroxy) and R.sup.14p is hydrogen or (1-4C)alkyl; [0149] wherein ARp is optionally substituted phenyl, optionally substituted phenyl(1-4C)alkyl, optionally substituted naphthyl, optionally substituted 5- or 6-membered heteroaryl; [0150] wherein ARp is also 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; [0151] wherein CYp is selected from:- [0152] (i) 4-, 5- or 6-membered cycloalkyl ring; [0153] (ii) 5- or 6-membered cycloalkenyl ring; [0154] (iii) 5- or 6-membered heteroaryl, 5- or 6-membered heteroaryloxy, 5- or 6-membered heteroaryl-S(O).sub.q--, 5- or 6-membered heteroarylamino [and (partially) hydrogenated versions thereof] and [0155] (iv) 5/6 or 6/6 bicyclic heteroaryl, 5/6 or 6/6 bicyclic heteroaryloxy, 5/6 or 6/6 bicyclic heteroaryl-S(O).sub.q--, 5/6 or 6/6 bicyclic heteroarylamino [and (partially) hydrogenated versions thereof]; [0156] wherein q is 0, 1 or 2 and any of the aforementioned ring systems in CYp may be optionally substituted by up to three substituents independently selected from halo, (1-4C)alkyl [including geminal disubstitution when CYp is a cycloalkyl or cycloalkenyl ring], acyl, oxo and nitro-(1-4C)alkyl; and pharmaceutically-acceptable salts thereof. [0157] In this embodiment (IP) of the specification the term `alkyl` includes straight chained and branched structures. For example, (1-6C)alkyl includes propyl, isopropyl and tert-butyl. However, references to individual alkyl groups such as "propyl" are specific for the straight chained version only, and references to individual branched chain alkyl groups such as "isopropyl" are specific for the branched chain version only. A similar convention applies to other radicals, for example halo(1-4C)alkyl includes 1-bromoethyl and 2-bromoethyl. [0158] In this embodiment (IP) of the specification a `5- or 6-membered heteroaryl` and `heteroaryl (monocyclic) ring` means a 5- or 6-membered aryl ring wherein (unless stated otherwise) 1, 2 or 3 of the ring atoms are selected from nitrogen, oxygen and sulfur. Unless stated otherwise, such rings are fully 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. Continue reading... Full patent description for Substituted isoxazolines and their use as antibacterial agents Brief Patent Description - Full Patent Description - Patent Application Claims Click on the above for other options relating to this Substituted isoxazolines and their use as antibacterial agents patent application. ###  How KEYWORD MONITOR works... a FREE service from FreshPatents1. Sign up (takes 30 seconds). 2. Fill in the keywords to be monitored. 3. Each week you receive an email with patent applications related to your keywords. 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