Patent ID: 7087629
Filing Date: 2006-08-08
Classification: A61P,C07D,C07F

Abstract:
1. A compound of formula (I), or a pharmaceutically acceptable salt, or an in-vivo hydrolysable ester thereof, wherein 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 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; Q is Q3 wherein B 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); (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) (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) -(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) (TBb) —NRv (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) R wherein R (TBda) CY1 or CY2; (TBdb) hydrogen, (1–4C)alkoxycarbonyl, trifluoromethyl, 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) wherein Rv is hydrogen or (1–4C)alkyl; Rw is hydrogen or (1–4C)alkyl; Rv (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 sp (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 (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 (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 sp (i) fully saturated other than (where appropriate) at a linking sp (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 (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 sp (i) fully saturated other than (where appropriate) at a linking sp (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 (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 by up to three substituents independently selected from (1–4C)alkyl {optionally substituted by one substituent selected independently from hydroxy, trifluoromethyl, (1–4C)alkylS(O) (1–4C)alkylS(O) (Rc2) R (Rc2a) AR1, AR2, AR2a, AR2b, AR3, AR3a, AR3b, AR4, AR4a, CY1, CY2; (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; (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) (Rc2d) R (Rc2e) R (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 X wherein R (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; Rh 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 quatemised, 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.