2-Pyridone Derivatives As Neutrophil Elastase Inhibitors And Their Use
First Claim
Patent Images
1. A compound of formula (I) wherein:
- Y represents CR3 or N;
R1 represents H or C1 to 6 alkyl;
R2 represents phenyl or a five- or six-membered heteroaromatic ring containing 1 to 4 heteroatoms independently selected from O, S and N;
said aromatic ring being optionally substituted by 1 to 3 substituents selected independently from OH, halogen, C1 to 6 alkyl, C1 to 6 alkoxy, NR58COR50, COOR51, COR52, CONR53R54 and NR47R48;
said alkyl being optionally further substituted by OH, C1 to 6 alkoxy, CN or CO2R49;
R47 and R48 independently represent H, C1 to 6 alkyl or C2 to 6 alkanoyl;
R3 represents H or F;
G1 represents phenyl or a five- or six-membered heteroaromatic ring containing 1 to 3 heteroatoms independently selected from O, S and N;
R5 represents H, halogen, C1 to 6 alkyl, CN, C1 to 6 alkoxy, NO2, NR14R15, C1 to 3 alkyl substituted by one or more F atoms or C1 to 3 alkoxy substituted by one or more F atoms;
R14 and R15 independently represent H or C1 to 3 alkyl;
said alkyl being optionally further substituted by one or more F atoms;
n represents an integer 1, 2 or 3 and when n represents 2 or 3, each R5 group is selected independently;
R4 represents H or C1 to 6 alkyl;
said alkyl being optionally further substituted by OH or C1 to 6 alkoxy;
or R4 and L are joined together such that the group —
NR4L represents a 5 to 7 membered azacyclic ring optionally incorporating one further heteroatom selected from O, S and NR16;
L represents a bond, O, S(O)p, NR29 or C1 to 6 alkyl;
said alkyl optionally incorporating a heteroatom selected from O, S and NR16; and
said alkyl being optionally further substituted by OH or OMe;
G2 represents a monocyclic ring system selected from;
i) phenyl or phenoxy, ii) a 5 or 6 membered heteroaromatic ring containing one to three heteroatoms independently selected from O, S and N, iii) a C3 to 6 saturated or partially unsaturated cycloalkyl, or iv) a C4 to 7 saturated or partially unsaturated heterocyclic ring containing one or two heteroatoms independently selected from O, S(O)p and NR17 and optionally further incorporating a carbonyl group;
or G2 represents a bicyclic ring system in which each of the two rings is independently selected from;
i) phenyl, ii) a 5 or 6 membered heteroaromatic ring containing one to three heteroatoms independently selected from O, S and N, iii) a C3 to 6 saturated or partially unsaturated cycloalkyl, or iv) a C4 to 7 saturated or partially unsaturated heterocyclic ring containing one or two heteroatoms independently selected from O, S(O)p and NR17 and optionally further incorporating a carbonyl group;
and the two rings are either fused together, or are bonded directly together or are separated by a linker group selected from O, S(O)q or CH2,
said monocyclic or bicyclic ring system being optionally further substituted by one to three substituents independently selected from CN, OH, C1 to 6 alkyl, C1 to 6 alkoxy, halogen, NR18R19, NO2, OSO2R38, CO2R20, C(═
NH)NH2, C(O)NR21R22, C(S)NR23R24, SC(═
NH)NH2, NR31C(═
NH)NH2, S(O)sR25, SO2NR26R27, C1 to 3 alkoxy substituted by one or more F atoms and C1 to 3 alkyl substituted by SO2R39, NR56R57 or by one or more F atoms;
or when L does not represents a bond, G2 may also represent H;
at each occurrence, p, q, s and t independently represent an integer 0, 1 or 2;
R18 and R19 independently represent H, C1 to 6 alkyl, formyl, C2 to 6 alkanoyl, S(O)tR32 or SO2NR33R34;
said alkyl group being optionally further substituted by halogen, CN, C1 to 4 alkoxy or CONR41R42;
R25 represents H, C1 to 6 alkyl or C3 to 6 cycloalkyl;
said alkyl group being optionally further substituted by one or more substituents selected independently from OH, CN, CONR35R36, CO2R37, OCOR40, C3 to 6 cycloalkyl, a C4 to 7 saturated heterocyclic ring containing one or two heteroatoms independently selected from O, S(O)p and NR43 and phenyl or a 5 or 6 membered heteroaromatic ring containing one to three heteroatoms independently selected from O, S and N;
said aromatic ring being optionally further substituted by one or more substituents selected independently from halogen, CN, C1 to 4 alkyl, C1 to 4 alkoxy, OH, CONR44R45, CO2R46, S(O)sR55 and NHCOCH3;
R32 represents H, C1 to 6 alkyl or C3 to 6 cycloalkyl;
R16, R17, R20, R21, R22, R23, R24, R26, R27, R29, R31, R33, R34, R35, R36, R37, R38, R39, R40, R41, R42, R43, R44, R45, R46, R49, R50, R51, R52, R53, R54, R55, R56, R57 and R58 independently represent H or C1 to 6 alkyl;
or a pharmaceutically acceptable salt thereof.
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Accused Products
Abstract
There are provided novel compounds of formula (I), wherein R1, R2, R4, R5, G1, G2, L, Y and n are as defined in the Specification and optical isomers, racemates and tautomers thereof, and pharmaceutically acceptable salts thereof; together with processes for their preparation, compositions containing them and their use in therapy. The compounds are inhibitors of neutrophil elastase.
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Citations
14 Claims
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1. A compound of formula (I)
wherein: -
Y represents CR3 or N;
R1 represents H or C1 to 6 alkyl;
R2 represents phenyl or a five- or six-membered heteroaromatic ring containing 1 to 4 heteroatoms independently selected from O, S and N;
said aromatic ring being optionally substituted by 1 to 3 substituents selected independently from OH, halogen, C1 to 6 alkyl, C1 to 6 alkoxy, NR58COR50, COOR51, COR52, CONR53R54 and NR47R48;
said alkyl being optionally further substituted by OH, C1 to 6 alkoxy, CN or CO2R49;
R47 and R48 independently represent H, C1 to 6 alkyl or C2 to 6 alkanoyl;
R3 represents H or F;
G1 represents phenyl or a five- or six-membered heteroaromatic ring containing 1 to 3 heteroatoms independently selected from O, S and N;
R5 represents H, halogen, C1 to 6 alkyl, CN, C1 to 6 alkoxy, NO2, NR14R15, C1 to 3 alkyl substituted by one or more F atoms or C1 to 3 alkoxy substituted by one or more F atoms;
R14 and R15 independently represent H or C1 to 3 alkyl;
said alkyl being optionally further substituted by one or more F atoms;
n represents an integer 1, 2 or 3 and when n represents 2 or 3, each R5 group is selected independently;
R4 represents H or C1 to 6 alkyl;
said alkyl being optionally further substituted by OH or C1 to 6 alkoxy;
or R4 and L are joined together such that the group —
NR4L represents a 5 to 7 membered azacyclic ring optionally incorporating one further heteroatom selected from O, S and NR16;
L represents a bond, O, S(O)p, NR29 or C1 to 6 alkyl;
said alkyl optionally incorporating a heteroatom selected from O, S and NR16; and
said alkyl being optionally further substituted by OH or OMe;
G2 represents a monocyclic ring system selected from;
i) phenyl or phenoxy, ii) a 5 or 6 membered heteroaromatic ring containing one to three heteroatoms independently selected from O, S and N, iii) a C3 to 6 saturated or partially unsaturated cycloalkyl, or iv) a C4 to 7 saturated or partially unsaturated heterocyclic ring containing one or two heteroatoms independently selected from O, S(O)p and NR17 and optionally further incorporating a carbonyl group;
orG2 represents a bicyclic ring system in which each of the two rings is independently selected from;
i) phenyl, ii) a 5 or 6 membered heteroaromatic ring containing one to three heteroatoms independently selected from O, S and N, iii) a C3 to 6 saturated or partially unsaturated cycloalkyl, or iv) a C4 to 7 saturated or partially unsaturated heterocyclic ring containing one or two heteroatoms independently selected from O, S(O)p and NR17 and optionally further incorporating a carbonyl group;
and the two rings are either fused together, or are bonded directly together or are separated by a linker group selected from O, S(O)q or CH2,
said monocyclic or bicyclic ring system being optionally further substituted by one to three substituents independently selected from CN, OH, C1 to 6 alkyl, C1 to 6 alkoxy, halogen, NR18R19, NO2, OSO2R38, CO2R20, C(═
NH)NH2, C(O)NR21R22, C(S)NR23R24, SC(═
NH)NH2, NR31C(═
NH)NH2, S(O)sR25, SO2NR26R27, C1 to 3 alkoxy substituted by one or more F atoms and C1 to 3 alkyl substituted by SO2R39, NR56R57 or by one or more F atoms;
or when L does not represents a bond, G2 may also represent H;
at each occurrence, p, q, s and t independently represent an integer 0, 1 or 2;
R18 and R19 independently represent H, C1 to 6 alkyl, formyl, C2 to 6 alkanoyl, S(O)tR32 or SO2NR33R34;
said alkyl group being optionally further substituted by halogen, CN, C1 to 4 alkoxy or CONR41R42;
R25 represents H, C1 to 6 alkyl or C3 to 6 cycloalkyl;
said alkyl group being optionally further substituted by one or more substituents selected independently from OH, CN, CONR35R36, CO2R37, OCOR40, C3 to 6 cycloalkyl, a C4 to 7 saturated heterocyclic ring containing one or two heteroatoms independently selected from O, S(O)p and NR43 and phenyl or a 5 or 6 membered heteroaromatic ring containing one to three heteroatoms independently selected from O, S and N;
said aromatic ring being optionally further substituted by one or more substituents selected independently from halogen, CN, C1 to 4 alkyl, C1 to 4 alkoxy, OH, CONR44R45, CO2R46, S(O)sR55 and NHCOCH3;
R32 represents H, C1 to 6 alkyl or C3 to 6 cycloalkyl;
R16, R17, R20, R21, R22, R23, R24, R26, R27, R29, R31, R33, R34, R35, R36, R37, R38, R39, R40, R41, R42, R43, R44, R45, R46, R49, R50, R51, R52, R53, R54, R55, R56, R57 and R58 independently represent H or C1 to 6 alkyl;
or a pharmaceutically acceptable salt thereof. - View Dependent Claims (2, 3, 4, 6, 7, 10, 11, 12, 13, 14)
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5. (canceled)
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8-9. -9. (canceled)
Specification