1-phenyl-2-pyridinyl alkyl alcohol derivatives as phosphodiesterase inhibitors

A compound represented by formula (I):

• wherein:
• R1 and R2 are the same or different and are independently:
• H;
• linear or branched (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;
• linear or branched (C2-C6) alkenyl;
• or
• linear or branched (C2-C6) alkynyl.
• R3 is H, CN, NO2, CF3, or a halogen atom;
• Z is a group (CH2)m wherein m=0 or 1;
• A is a phenyl ring, which is optionally substituted by one or more substituents R4, which may be the same or different and are independently:
• linear or branched (C1-C6) alkyl optionally substituted by one or more (C3-C7) cycloalkyl or (C3-C7)heterocycloalkyl;
• (C1-C6) haloalkyl;
• (C1-C6) alkylthio;
• halogen;
• NH2;
• or
• OR7 wherein R7 is:
• H;
• (C1-C10) alkyl optionally substituted by a radical selected from the group consisting of (C3-C7) cycloalkyl, (C3-C7) heterocycloalkyl, aryl and heteroaryl;
• (C1-C10) alkyl substituted by one group OH;
• (C1-C6) haloalkyl;
• (C3-C7) cycloalkyl;
• (C1-C4)alkylaminocarbonyl;
• (C1-C4)alkyloxycarbonyl;
• (C3-C7) heterocycloalkyl optionally substituted by (C1-C4) alkyl;
• or
• R5R6N—(C1-C10)alkylene wherein R5 and R6 are independently H or linear or branched (C1-C6) alkyl, or, together with the nitrogen atom to which they are linked, R5 and R6 form a saturated, partially saturated or unsaturated ring, wherein said ring is optionally substituted by (C1-C4) alkyl, halogen atoms, or R7R8N—(C1-C4)alkylene wherein R7 and R8 are the same or different and are independently H or linear or branched (C1-C6) alkyl, or, together with the nitrogen atom to which they are linked, R7 and R8 form a saturated or partially saturated ring;
• W is:
• —NR9SO2R10 wherein
• R9 is:
• (C1-C10) alkyl optionally substituted by (C3-C7) cycloalkyl, (C3-C7) heterocycloalkyl, (C3-C7) heterocycloalkylcarbonyl, wherein any such ring may be optionally substituted by one or more (C1-C4) alkyl or OH;
• or
• R11R12N—(C1-C10)alkylene wherein R11 and R12 are independently H or (C1-C6) alkyl, each of which may optionally be substituted by a group OH;
• and
• R10 is:
• (C1-C4) alkyl optionally substituted by (C3-C7) cycloalkyl;
• (C3-C7)cycloalkyl;
• or
• phenyl, any of which may be optionally substituted with one or more halogen atoms or (C1-C4) alkyl group;
• —CH2NR13SO2R14 wherein
• R13:
• H;
• (C3-C7) cycloalkyl;
• (C1-C10) alkyl optionally substituted by (C3-C7) cycloalkyl, (C3-C7) heterocycloalkyl, where any such ring may be optionally substituted by (C1-C4) alkyl;
• or
• R11R12N—(C1-C10)alkylene wherein R11 and R12 are independently H or (C1-C6) alkyl, each of which may optionally be substituted by a group OH;
• R14 is:
• (C1-C4) alkyl;
• (C3-C7) heterocycloalkyl-(C1-C4)alkylene;
• or
• phenyl, any of which may be optionally substituted with one or more halogen atoms or (C1-C4) alkyl group;
• —(C1-C4)alkylene-(C3-C7)heterocycloalkyl, which may be optionally substituted by one or more groups selected from the group consisting of oxo, OH, SH, (C1-C4) alkyl, and hydroxy(C1-C6)alkylene;
• —(C3-C7) heterocycloalkyl ring, which may be optionally substituted by one or more groups selected from the group consisting of oxo, OH, SH, (C1-C4) alkyl, and hydroxy(C1-C6)alkylene;
• —(C1-C4)alkylene-amino-(C3-C7)heterocycloalkyl, which may be optionally substituted by one or more groups selected from the group consisting of oxo, OH, SH, (C1-C4) alkyl, and hydroxy(C1-C6)alkylene
• —SO2NR15R16 wherein
• R15 is H or (C1-C10) alkyl;
• and
• R16 is:
• (C1-C10) alkyl which is optionally substituted by (C3-C7) cycloalkyl or (C3-C7) heterocycloalkyl, where any such ring may be optionally substituted by (C1-C4) alkyl;
• or
• R11R12N—(C1-C10)alkylene wherein R11 and R12 are independently H or (C1-C6) alkyl, each of which may optionally be substituted by a group OH;
• or
• R15 and R16, together with the nitrogen atom to which they are linked, form a (C3-C7) heterocycloalkyl ring optionally substituted by one or more (C1-C4) alkyl;
• —NHSO2R17 wherein
• R17 is:
• (C1-C10) alkyl which is optionally substituted by (C3-C7)cycloalkyl, (C3-C7) heterocycloalkyl, aryl, or heteroaryl ring, where any such ring may be optionally substituted by (C1-C4) alkyl;
• or
• R11R12N—(C1-C10)alkylene wherein R11 and R12 are independently H or (C1-C6) alkyl, each of which may optionally be substituted by a group OH;
• —OSO2R18 wherein
• R18 is:
• (C1-C10) alkyl which is optionally substituted by halogen, OH, (C1-C4) alkoxyl, (C3-C7) cycloalkyl, (C3-C7) heterocycloalkyl, aryl, or heteroaryl, where any such ring may be optionally substituted by (C1-C4) alkyl;
• or
• R11R12N—(C1-C10)alkylene wherein R11 and R12 are independently H or (C1-C6) alkyl, each of which may optionally be substituted by a group OH;
• —OC(O)R19 wherein
• R19 is:
• (C3-C7) cycloalkyl, (C3-C7) heterocycloalkyl, where any such ring may be optionally substituted by (C1-C4) alkyl;
• (C1-C10) alkyl which is optionally substituted by one or more of halogen, OH, NH2, (C3-C7) cycloalkyl, or (C3-C7) heterocycloalkyl, where any such ring may be optionally substituted by (C1-C4) alkyl;
• or
• R11R12N—(C1-C10)alkylene wherein R11 and R12 are independently H or (C1-C6) alkyl, each of which may optionally be substituted by a group OH;
• —C(O)R20 wherein
• R20 is:
• —NR21R22 wherein R21 and R22 are independently H, (C1-C6) alkyl, (C3-C7) cycloalkyl, or (C3-C7)heterocycloalkyl(C1-C4)alkylene, each of which may optionally be substituted by (C1-C4) alkyl, OH, or NH2, or, together with the nitrogen atom to which they are linked, R21 and R22 form a saturated or partially saturated heterocyclic ring which may be optionally substituted by (C1-C4) alkyl, OH, or NH2;
• —OR23 wherein R23 is (C1-C10) alkyl which is substituted by one or more of halogen, OH, (C3-C7)cycloalkyl, or (C3-C7)heterocycloalkyl, where any such ring may be optionally substituted by (C1-C4) alkyl;
• —NH—(C1-C4)alkylene-NR24R25 wherein
• R24 and R25, the same or different, are independently H or (C1-C6) alkyl, or, together with the nitrogen atom to which they are linked, R24 and R25 form a saturated or partially saturated ring, which is optionally substituted by one ore more (C1-C4) alkyl groups;
• —NHCOR26 wherein
• R26 is:
• R27R28N—(C1-C6)alkylene wherein R27 and R28 are the same or different and are independently H or (C1-C6) alkyl optionally substituted by OH or NH2, or, together with the nitrogen atom to which they are linked, R27 and R28 form a saturated or partially saturated ring, which is optionally substituted by one or more (C1-C4) alkyl, OH, or NH2 groups;
• R27R28N-carbonyl-(C1-C6)alkylene wherein R27 and R28 are the same or different and are independently H or (C1-C6) alkyl optionally substituted by OH or NH2, or, together with the nitrogen atom to which they are linked, R27 and R28 form a saturated or partially saturated ring, which is optionally substituted by one or more (C1-C4) alkyl, OH, or NH2 groups;
• or
• (C3-C7) heterocycloalkyl ring, which may be optionally substituted by one or more groups selected from the group consisting of oxo, OH, SH, and hydroxy(C1-C6)alkylene;
• —NH—(C1-C4)alkylene-OR29 wherein R29 is H or (C1-C6) alkyl;
• —CH2OC(O)R30 wherein R30 is selected from a (C1-C10) alkyl which is substituted by one or more halogen, OH, (C3-C7) heterocycloalkyl optionally substituted by OH or (C1-C4) alkyl
• —CH2OC(O)R30 wherein
• R30 is:
• (C3-C7) cycloalkyl,
• (C3-C7) heterocycloalkyl where any such ring may be optionally substituted by (C1-C4) alkyl;
• (C1-C10) alkyl which is substituted by one or more halogen, OH, (C3-C7) cycloalkyl, (C3-C7) heterocycloalkyl where any such ring may be optionally substituted by OH or (C1-C4) alkyl;
• or
• R11R12N—(C1-C10)alkylene wherein R11 and R12 are independently H or (C1-C6) alkyl, each of which may optionally be substituted by a group OH
• or an N-oxide on the pyridine ring, or a pharmaceutically acceptable salt thereof.