Derivatives of 1-phenyl-2-pyridinyl alkyl alcohols as phosphodiesterase inhibitors

A method of treating a disease of the respiratory tract characterized by airway obstruction, said method comprising administering to a subject in need thereof an effective amount of a compound of formula (I):

• wherein:
• Z is (CH2)m;
• (CH2)n;
• O(CH2)p;
• CH2SO2;
• CHNR6;
• CH2NR6;
• NR6;
• OCOR4R5;
• or CR4R5,
• wherein m=0, 1, or 2;
• n=1, 2, or 3;
• p=0, 1, 2 or 3;
• R4 is independently H or linear or branched (C1-C4) alkyl;
• R5 is independently selected from the group consisting of linear or branched (C1-C4) alkyl;
• phenyl;
• benzyl;
• NH2;
• and HNCOOR′, wherein R′ is linear or branched (C1-C4) alkyl;
• or R4 and R5, together with the carbon to which they are linked, form a ring having 3, 4, or 5 carbons
• R6 is H or a linear or branched (C1-C4) alkyl;
• R1 and R2 are the same or different and are each independently H;
• linear or branched (C1-C6) alkyl, optionally substituted by one or two substituents selected from the group consisting of a fluorine atom and a chlorine atom, or optionally substituted by one or more substituents selected from the group consisting of a (C3-C7) cycloalkyl and (C5-C7) cycloalkenyl;
• (C3-C7) cycloalkyl;
• (C5-C7) cycloalkenyl;
• linear or branched (C2-C6) alkenyl;
• or linear or branched (C2-C6) alkynyl;
• R3 is one or more substituents independently selected from the group consisting of H, CN, NO2, CF3 and a halogen atom;
• A is a mono- or bicyclic, saturated, partially unsaturated, or unsaturated ring system, having 5 to 10 ring atoms, which may be optionally substituted with one or more Rx groups, wherein each Rx may be the same or different and each Rx is independently:
• linear or branched (C1-C6) alkyl or (C3-C7) cycloalkyl;
• linear or branched (C2-C6) alkenyl optionally substituted by one or more (C3-C7) cycloalkyl;
• linear or branched (C2-C6) alkynyl optionally substituted by one or more (C3-C7) cycloalkyl;
• (C5-C7) cycloalkenyl;
• phenyl;
• (C3-C7) heterocycloalkyl;
• OR7, wherein R7 is:
• H;
• (C1-C10) alkyl optionally substituted by (C3-C7) cycloalkyl;
• (C3-C7) cycloalkyl;
• (C1-C4) alkylene-(C3-C7) heterocycloalkyl;
• CO(C1-C6) alkyl;
• COO(C1-C6) alkyl;
• phenyl;
• benzyl;
• or
• (C1-C10) alkylene-NR8R9, wherein R8 and R9 are each independently H or linear or branched (C1-C6) alkyl, or R8 and R9 together with the nitrogen atom to which they are linked form a saturated, partially saturated, or unsaturated ring, optionally substituted by (C1-C4) alkyl;
• a halogen atom;
• CN;
• NO2;
• NR10R11, wherein R10 and R11 may be the same or different and are each independently:
• H;
• linear or branched (C1-C6) alkyl, phenyl or (C3-C7) cycloalkyl;
• COC6H5
• CO—(C1-C4) alkyl;
• COO—(C1-C4) alkyl;
• CONH—(C1-C6) alkylene-R12, wherein R12 is selected from the group consisting of H;
• (C1-C4) alkyl;
• and OR4R5;
• or
• CONH(C1-C4) alkylene-N(C1-C4) alkyl;
• or R10 and R11 together with the nitrogen atom to which they are linked form a saturated or partially saturated ring;
• (C1-C4) alkylene-NR10R11;
• COR12, wherein R12 is phenyl or linear or branched (C1-C6) alkyl;
• oxo;
• HNSO2R13, wherein R13 is (C1-C4) alkyl or a phenyl optionally substituted with one or more halogen atoms or with a (C1-C4) alkyl group;
• SO2R14, wherein R14 is (C1-C4) alkyl, OH, or NR10R11 wherein R10 and R11 are as defined above;
• SOR15, wherein R15 is phenyl or (C1-C4) alkyl;
• SR16, wherein R16 is H, phenyl, or (C1-C4) alkyl;
• COOR17, wherein R17 is H, (C1-C4) alkyl, phenyl, or benzyl;
• or
• (CH2)qOR18, wherein q=1, 2, 3, or 4 and R18 is H, or a pharmaceutically acceptable salt thereof or a N-oxide of the pyridine ring thereof.