| 主权项 |
1. A method of treating a disease or condition selected from the group consisting of chronic eosinophilic pneumonia, asthma, COPD, adult respiratory distress syndrome (ARDS), exacerbation of airways hyper-reactivity consequent to other drug therapy, and airways disease that is associated with pulmonary hypertension, comprising administering, to a subject in need thereof, an effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof:wherein
W is N substituted with —H; Y is —O—; R1 is a group (IIc): X2, X3, X4 and X5 are each independently a carbon atom, a nitrogen atom, a group —(CH)— or a group —NH—; such that each combination thereof forms an aromatic ring system; R11 is linked to X4 and is selected from the group consisting of —NRARB; —N(RC)(C2-C6alkylene)-NRARB; —N(RC)(C3-C7cycloalkylene)-NRARB; —(C1-C6alkylene)-NRARB; —(C3-C7cycloalkylene)-NRARB; and (C3-C7)heterocycloalkyl, wherein said (C3-C7)heterocycloalkyl may be optionally substituted with one, two, or three C1-C6 alkyl groups; RA and RB are at each occurrence independently —H, C1-C6 alkyl or C3-C7 cycloalkyl, said C1-C6 alkyl and C3-C7 cycloalkyl being optionally substituted by a group C1-C3 alkyl C3-C7cycloalkyl, —ORD, —CN or halo; alternatively, RA and RB, may form together with the nitrogen atom to which they are attached an azetidine or a 4-11-membered saturated heterocyclic monocyclic or bicyclic ring system which is optionally substituted by one or more groups —ORD, —CN, halo, C1-C6 alkyl, (C1-C6)hydroxyalkyl or C3-C7 cycloalkyl, said C1-C6 alkyl and C3-C7 cycloalkyl being optionally substituted by a group C1-C3 alkyl, C3-C7cycloalkyl, —ORD, —CN or halo; and which 4-11-membered saturated heterocyclic monocyclic or bicyclic ring optionally contains a further heteroatom which is oxygen or nitrogen, said nitrogen atom optionally substituted by C1-C6 alkyl or C3-C6 cycloalkyl, wherein any of said C1-C6 alkyl or C3-C6 cycloalkyl may be optionally substituted by a group C1-C6 alkyl, C3-C7 cycloalkyl, —ORD, —CN, or halo; or RA and RB may be linked to one carbon atom of the —(C1-C6alkylene)-, —(C2-C6alkylene)- or —(C3-C7cycloalkylene)- portion of the group linked to the nitrogen to which they are connected to form a saturated cycle of up to 6 ring atoms; RC is at each occurrence independently —H, C1-C6 alkyl, (C1-C4)hydroxyalkyl or C3-C6 cycloalkyl, said C1-C6 alkyl and C3-C6 cycloalkyl being optionally substituted by a group C1-C3 alkyl, —ORD, —CN or halo; alternatively RC may be linked to one carbon atom of the —(C2-C6alkylene)- or —(C3-C7cycloalkylene)- portion of the group linked to the nitrogen to which they are connected to form a saturated cycle of up to 6 ring atoms RD is at each occurrence independently —H, —CH3 or —C2H5; R13 is —H, C1-C6 alkyl, or halogen; A is a divalent cycloalkylene radical having 6 ring atoms; said cycloalkylene ring being attached to W and Y and fused to a phenyl ring; R2 is a radical of formula (IIIb): wherein R17 is a group of general formula (IV) wherein R20 is —CH3; R21 is —CH3; R18 is selected from the group consisting of aryl and heteroaryl, wherein any of said aryl or heteroaryl is substituted by two or more groups independently selected from the group consisting of —CN, —OH, ═O, halo, C1-C6 alkyl, —O—(C1-C6alkyl), —(C1-C6alkylene)-NRHRJ, and —O—(C2-C6alkylene)-NRHRJ, wherein any of said C1-C6alkyl portion in the above listed groups may be optionally substituted by a group —ORL; RH and RJ are each C1-C6 alkyl; alternatively, RH and RJ may form together with the nitrogen atom to which they are attached a 4-11-membered saturated monocyclic or bicyclic heterocyclic ring system which is optionally substituted by one or more groups —ORM or NRORP; and which 4-11-membered saturated monocyclic or bicyclic heterocyclic ring optionally contains a further heteroatom which is oxygen or nitrogen, said nitrogen atom optionally substituted by C1-C6 alkyl; RL is —H; RM is at each occurrence independently —H or C1-C6 alkyl; RO and RP are each C1-C6 alkyl; and z1 is CH, z2 is C, and z3 and z4 are N. |
