| 主权项 |
1: A method of treating a disease or condition in which HNE is implicated, comprising administering, to a subject in need thereof, an effective amount of a compound of formula (I): wherein A is CH or N; B is CH or N; D is CH or N; R1 is: hydrogen; (C1-C6)alkyl; NR7R8(C1-C6)alkyl; (C1-C4)alkenyl; phenyl(C1-C6)alkyl wherein said phenyl ring is optionally substituted by a NR15R16(C1-C6)alkyl or by N+R15R16R17(C1-C6)alkyl; a group —CH2(CH2)nOH; a group —(CH2)nCONR5R6; a group —(CH2)nSO2NR5R6; a group —CH2—(CH2)nNR5SO2R6; a group —(CH2)t—(C6H4)—SO2(C1-C4)alkyl; group —(CH2)rSO2(C1-C4)alkyl wherein the (C1-C4)alkyl is optionally substituted by —NR15R16 or —N+R15R16R17; a group —SO2-phenyl wherein the phenyl ring is optionally substituted by NR7R8(C1-C6)alkyl; or a group —(CH2)n—W wherein W is a 5-6-membered heteroaryl ring which is optionally substituted by —SO2(C1-C4)alkyl; n is 1, 2 or 3; t is zero, 1, 2 or 3; r is zero, 1, 2, 3 or 4; R5 is: hydrogen, (C1-C6)alkyl, NR16R15(C1-C6)alkyl or N+R17R15R16(C1-C6)alkyl; R6 is hydrogen or (C1-C6)alkyl; R7 is: hydrogen, (C1-C6)alkyl, (C1-C6)alkylcarbonyl, —SO2(C1-C4)alkyl, or NR16R15(C1-C6)alkyl; R8 is hydrogen or (C1-C6)alkyl; alternatively, R7 and R8 may form, together with the nitrogen atom to which they are attached, a (C5-C7)heterocycloalkyl ring system which is optionally substituted by one or more (C1-C6) alkyl groups or oxo; R16 is hydrogen or (C1-C6)alkyl; R15 is hydrogen or (C1-C6)alkyl; R17 is hydrogen or (C1-C6)alkyl; R3 is a group cyano or —C(O)—XR4; X is: —O—, —(CH2)—, or —NH—; R4 is: hydrogen; (C1-C6)alkyl; a group of formula -[Alk1]-Z wherein Alk1 represents a(C1-C4)alkylene radical and Z is:
(i) —NR9R10 wherein R9 and R10 are independently hydrogen, (C1-C6)alkyl or (C3-C6)cycloalkyl group, wherein the (C1-C6)alkyl or(C3-C6)cycloalkyl group are optionally substituted by one to four R35 groups which are at each occurrence independently selected from the group consisting of: (C1-C6)alkyl, (C1-C6)alkoxyl, hydroxyl, hydroxyl-C1-C6-alkyl, halo, trifluoromethyl, and trifluoromethoxy; or, taken together with the nitrogen to which they are attached, form a monocyclic (C5-C7)heterocyclic ring which may contain a further heteroatom selected from N, O, and S and which is optionally substituted by one to four R35 groups which are at each occurrence independently selected from the group consisting of: (C1-C6)alkyl, (C1-C6)alkoxyl, hydroxyl, hydroxyl-C1-C6-alkyl, halo, trifluoromethyl, and trifluoromethoxy;
or (ii) —N+R11R12R13 wherein R11, R12 and R13 are each independently (C1-C6)alkyl or (C3-C6)cycloalkyl group, wherein the (C1-C6)alkyl or (C3-C6)cycloalkyl group are optionally substituted by one to four R36 groups which are at each occurrence independently selected from the group consisting of: (C1-C6)alkyl, (C1-C6)alkoxyl, hydroxyl, hydroxyl-C1-C6-alkyl, halo, trifluoromethyl, and trifluoromethoxy; or any two of R11, R12 and R13 taken together with the nitrogen to which they are attached form a monocyclic (C5-C7)heterocyclic ring which may contain a further heteroatom selected from N, O, and S and the other of R11, R12 and R13 is a (C1-C6)alkyl or an optionally substituted (C3-C6)cycloalkyl group, wherein the monocyclic (C5-C7)heterocyclic, (C1-C6)alkyl or (C3-C6)cycloalkyl group are optionally substituted by one to four R36 groups which are at each occurrence independently selected from the group consisting of: (C1-C6)alkyl, (C1-C6)alkoxyl, hydroxyl, hydroxyl-C1-C6-alkyl, halo, trifluoromethyl, and trifluoromethoxy; a radical of formula —(CH2)q-[Q]-(CH2)p Z wherein Z is as above defined, q is an integer ranging from zero to 3, p is an integer ranging from zero to 3 and Q represents a divalent group selected from: —O—, phenylene, (C5-C7)heterocycloalkylene, (C3-C6)cycloalkyl, and pyridinylene, wherein the phenylene, (C5-C7)heterocycloalkylene, (C3-C6)cycloalkyl and pyridinylene are optionally substituted by one to four R37 groups which are at each occurrence independently selected from the group consisting of: (C1-C6)alkyl, (C1-C6)alkoxyl, hydroxyl, hydroxyl-C1-C6-alkyl, halo, trifluoromethyl, and trifluoromethoxy; R2 is: R14O(C1-C6)alkyl; NR18R19(C1-C6)alkyl; —CONR21R20; C2-C6-alkenyl which may be optionally substituted by —OH or —NR18R19; C2-C6-alkynyl which may be optionally substituted by —OH or —NR18R19; or a group —[CH2]y-G-[CH2]j—CH2—N+R22R23R24 or R2 is a group: or R2 is a group: R14 is hydrogen or (C1-C6)alkyl which may be optionally substituted by a (C1-C4)alkoxyl group; R18 is hydrogen or (C1-C6)alkyl; R19 is hydrogen or (C1-C6)alkyl; R20 is: hydrogen, (C1-C6)alkyl, or (C1-C6)alkylNR18R19; R21 is hydrogen or (C1-C6)alkyl; j is an integer ranging from zero to 4; y is an integer ranging from zero to 4; G is a divalent linker selected from the group consisting of: —O—, —(SO2)—, NR25, a bond, C2-C6-alkenylene, C2-C6-alkynylene, (C3-C6)cycloalkylene, monocyclic heterocycloalkylene, bicyclic heterocycloalkylene, —[CONR25]— and —[NR25CO]—; R25 is hydrogen or (C1-C6)alkyl; R22 is: (C1-C6)alkyl, which is optionally substituted by one or more of (C3-C6)cycloalkyl, phenyl, benzyl, CN, —OR26, —SO2R26, —CO2R26, —CONR26R27 or —SO2NR26R27; (C3-C10)cycloalkyl which is optionally substituted by one or more of —OR26, —SO2R26, —CO2R26, —CONR26R27 or —SO2NR26R27; or (C4-C7)heterocycloalkyl which is optionally substituted by one or more of —OR26, —SO2R26, —CO2R26, —CONR26R27 or —SO2NR26R27; R26 is hydrogen or (C1-C6)alkyl; R27 is hydrogen or (C1-C6)alkyl; R23 is hydrogen or (C1-C6)alkyl, which (C1-C6)alkyl is optionally substituted by one or more of —OR29, —SO2R29, —CO2R29, —CONR29R30 or —SO2NR29R30; R24 is hydrogen or (C1-C6)alkyl, which (C1-C6)alkyl is optionally substituted by one or more of —OR31, —SO2R31, —CO2R31, —CONR31R32 or —SO2NR31R32; alternatively, R23 and R24 may form, together with the nitrogen atom to which they are attached, a 5-11-membered saturated monocyclic or bicyclic heterocyclic ring system which is optionally substituted by one or more of —OR28, halo, C1-C6 alkyl, —SO2R33, —CO2R33, —CONR33R34 or —SO2NR33R34; and which 5-11-membered saturated monocyclic or bicyclic ring optionally contains a further heteroatom which is oxygen or nitrogen or a —SO2— group; or R22 together with R23, R24 and the nitrogen atom to which they are attached, may form a bridged bicyclic heterocyclic ring; R28 is hydrogen or (C1-C6)alkyl; R29 is hydrogen or (C1-C6)alkyl; R30 is hydrogen or (C1-C6)alkyl; R31 is hydrogen or (C1-C6)alkyl; R32 is hydrogen or (C1-C6)alkyl; R33 is hydrogen or (C1-C6)alkyl; R34 is hydrogen or (C1-C6)alkyl; R38 represents one or two optional substituents at each occurrence independently selected from the group consisting of: (C1-C6)alkyl, (C1-C6)alkoxyl, hydroxyl, hydroxyl-C1-C6-alkyl, halo, trifluoromethyl, and trifluoromethoxy; wherein only two of A, B and D may be at the same time a nitrogen atom; wherein if one or more groups N+R11R12R13— or N+R15R16R17— are present, they form a quaternary salt with a pharmaceutically acceptable counter ion; and wherein groups R5 to R38, and n may have the same or different meanings at each occurrence, if present in more than one group, or a pharmaceutically acceptable salt thereof. |
