Carbamate derivatives

摘要

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

主权项

1. A compound of formula (I):wherein:
each R1 is the same or different and is independently hydrogen, halogen, (C1-C4) alkyl, (C1-C4) alkoxy, (C1-C4) haloalkyl, hydroxy, —SO2NRIRII, —CN, —N(RI)SO2RIII, —NRIRII, —C(O)NRIRII, or —N(RI)C(O)RIII, and wherein each said (C1-C4) alkyl is optionally substituted by one or more groups selected from the group consisting of (C3-C7) cycloalkyl, hydroxyl, and —NRIRII and wherein each said (C1-C4) alkoxy is optionally substituted by one or more halogen atoms or (C3-C7) cycloalkyl groups, and wherein: RI is hydrogen or (C1-C6) alkyl; RII is hydrogen or (C1-C6) alkyl; RIII is hydrogen or (C1-C6) alkyl; n is an integer ranging from 1 to 3; each R2 and each R3 is the same or different and is hydrogen, halogen, (C1-C4) alkyl, (C1-C4) alkoxy, (C1-C4) haloalkyl, hydroxy, —SO2NRIRII, —CN, —N(RI)SO2RIII, —NRIRII, —C(O)NRIRII, or —N(RI)C(O)RIII and wherein each said (C1-C4) alkyl is optionally substituted by one or more groups selected from the group consisting of (C3-C7) cycloalkyl, hydroxyl, and —NRIRII and wherein each said (C1-C4) alkoxy is optionally substituted by one or more halogen atoms or (C3-C7) cycloalkyl groups and wherein: RI, RII, and RIII are as defined above; m and m′ are the same of different and are independently an integer ranging from 1 to 3; each R4 and each R5 is the same or different and is 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 such phenyl ring: each R6 is the same or different and is CN, NO2, CF3 or a halogen atom; k is 0 or an integer ranging from 1 to 3; L1 is a bond, —C(O)—, —SO2—, or —(CH2)—; the groupis a divalent saturated monocyclic heterocycloalkylene, which contains at least one nitrogen atom, and which is linked to the L1 residue by one of its nitrogen atom;
L2 is: a bond; [1]-(CH2)q-[2]; [1]-C(O)NH—(CH2)q—NH—C(O)-[2]; [1]-C(O)O—(CH2)q—O—C(O)-[2]; [1]-(CH2)qO-[2]; [1]-O(CH2)q-[2]; [1]-(CH2)q—O—C(O)-[2]; [1]-C(O)O—(CH2)q [2]-; [1]-(CH2)q—NH—C(O)-[2]; or [1]-C(O)NH—(CH2)q [2]-; wherein q is an integer ranging from 1 to 4; and wherein [1] and [2] represent, respectively, the point of attachment of group L2 to a carbon atom of the phenylene ring (1) and to a carbon atom of the phenylene ring (2); and A is a nitrogen containing group which is:
a group (a) which is —(CH2)s—NR8R9 wherein s is an integer ranging from 1 to 4 and R8 and R9 are independently hydrogen or (C1-C4) alkyl; anda group (b) which is a saturated monocyclic, bicyclic, or tricyclic heterocyclic ring system optionally substituted by one or two groups R10 which are at each occurrence independently (C1-C4) alkyl or benzyl, an N-oxide on the pyridine ring, a deuterated derivative, or a pharmaceutically acceptable salt thereof.