Compounds

摘要

Compounds of formula (I) defined herein are both inhibitors of the phosphodiesterase 4 (PDE4) enzyme and muscarinic M3 receptor antagonists and are useful for the prevention and/or treatment of a disease of the respiratory tract characterized by airway obstruction.

主权项

1. A compound represented by formula (I):wherein
R1 is hydrogen, (C1-C4) alkyl, or —SO2(C1-C4)alkyl; R2 is aryl or a 5 to 11 membered heteroaryl, wherein said aryl or heteroaryl is optionally substituted by 1 to 3 groups at each occurrence independently selected from the group consisting of halogen, (C1-C4)haloalkyl, hydroxy, —SO2NR8R9, —CN, —NR10SO2R11, (C1-C4) alkyl, and (C1-C4) alkoxy, wherein said (C1-C4) alkyl or (C1-C4) alkoxy are optionally substituted by one (C3-C7) cycloalkyl group, and wherein
R8 is hydrogen or (C1-C6) alkyl;R9 is hydrogen or (C1-C6) alkyl;R10 is hydrogen or (C1-C6) alkyl;R11 is hydrogen or (C1-C6) alkyl; Z is a bond or a divalent radical selected from the group consisting of -(CH2)m—, —S—, —S(O)—, —S(O2)—, a group —C(O)—, and a group [1]-(CH2)m, —OC(O)-[2] wherein [1] and [2] represent, respectively the point of attachment of group Z to phenyl ring and to the nitrogen atom, and m is an integer ranging from 1 to 4; L1 is:
a bond,—(CH2)p—,[3]-(CH2)p—O-[4][3]-(CH2)p—NR10—(CH2)t-[4][3]-(CH2)p—OC(O)-[4][3]-(CH2)p—NR10C(O)-[4][3]-(CH2)p—NR10S(O2)—[4] or[3]-(CH2)p—S(O2)—N(R10)—[4] wherein [3] and [4] represent, respectively the point of attachment of group L1 to the carbonyl group and to the phenyl ring, and wherein
R10 is as described above,p is an integer ranging from 1 to 4 andt is an integer ranging from 1 to 4 each R3 is independently hydrogen, halogen, (C1-C4) haloalkyl, hydroxy, aminocarbonyl, di-(C1-C4) alkylaminocarbonyl, —SO2NR12R13, —CN, —NR14SO2R15, —(CH2)m—NR14SO2R15—, (C1-C4) alkyl, or (C1-C4) alkoxy, wherein said (C1-C4) alkyl or (C1-C4) alkoxy are optionally substituted by one (C3-C7) cycloalkyl group, m is as described above and
R12 is hydrogen or (C1-C6) alkyl;R13 is hydrogen or (C1-C6) alkyl;R14 is hydrogen or (C1-C6) alkyl;R15 is hydrogen or (C1-C6) alkyl; q is an integer ranging from 1 to 3; R4 and R5 are the same of different and are independently:
H;(C3-C7) cycloalkylcarbonyl;(C1-C6) alkyl, optionally substituted by one or more substituents selected from (C3-C7) cycloalkyl and (C5-C7) cycloalkenyl;(C1-C6) haloalkyl;(C3-C7) cycloalkyl;(C5-C7) cycloalkenyl;(C2-C6) alkenyl; or(C2-C6) alkynyl; or R4 and R5, together with the interconnecting atoms, form a 2,2-difluoro-1,3-dioxolane ring of formula (r) fused to the phenyl moiety which bears groups —OR4 and —OR5, wherein asterisks indicate carbon atoms shared with said phenyl ring: each R6 is independently CN, NO2, CF3, or a halogen atom; n is 0 or an integer ranging from 1 to 3; A is a nitrogen containing group which is:
a group (a) which is —(CH2)s—NR16R17 wherein s is an integer ranging from 1 to 4 and R16 and R17 are independently hydrogen or (C1-C4) alkyl; ora group (b) which is a saturated monocyclic, bicyclic or tricyclic heterocyclic ring system optionally substituted by one or two groups R18 which are at each occurrence independently selected from (C1-C4) alkyl and benzyl,or an N-oxide on the pyridine ring, a deuterated derivative, or a pharmaceutically acceptable salt thereof.