Novel Heterocyclic Derivatives and Their Use in the Treatment of Neurological Disorders

A compound of formula (IIa), or a salt thereof,

• in which
• Hal is halogen;
• PG is a protecting group;
• X1 is CR1 or N;
• X3 is CR3 or N;
• X4 is CR4 or N;
• X5 is CR5 or N;
• wherein at least one of X1, X3, X4 and X5 is N and not more than 2 of X1, X3, X4 and X5 are N;
• R1 is hydrogen, cyano, halogen, (C1-8)alkyl, halogen-(C1-8)alkyl, (C1-8)alkoxy, halogen-(C1-8)alkoxy, (C1-8)alkylthio, halogen-(C1-8)alkylthio, (C1-8)alkoxy-(C1-8)alkyl, (C1-8)alkoxy-(C1-8)alkoxy, (C1-8)alkoxy-(C1-8)alkylthio, (C1-8)alkylthio-(C1-8)alkyl, (C1-8)alkylthio-(C1-8)alkoxy, (C1-8)alkylthio-(C1-8)alkylthio, (C2-8)alkenyl, or (C2-8)alkynyl;
• R3 is hydrogen, cyano, halogen, (C1-8)alkyl, halogen-(C1-8)alkyl, (C1-8)alkoxy;
• halogen-(C1-8)alkoxy, (C1-8)alkylthio, halogen-(C1-8)alkylthio, (C1-8)alkoxy-(C1-8)alkyl, (C1-8)alkoxy-(C1-8)alkoxy, (C1-8)alkoxy-(C1-8)alkylthio, (C1-8)alkylthio-(C1-8)alkyl, (C1-8)alkylthio-(C1-8)alkoxy, (C1-8)alkylthio-(C1-8)alkylthio, (C2-8)alkenyl, or (C2-8)alkynyl;
• R4 is hydrogen, cyano, halogen, (C1-8)alkyl, halogen-(C1-8)alkyl, (C1-8)alkoxy, halogen-(C1-8)alkoxy, (C1-8)alkylthio, halogen-(C1-8)alkylthio, (C1-8)alkoxy-(C1-8)alkyl, (C1-8)alkoxy-(C1-8)alkoxy, (C1-8)alkoxy-(C1-8)alkylthio, (C1-8)alkylthio-(C1-8)alkyl, (C1-8)alkylthio-(C1-8)alkoxy, (C1-8)alkylthio-(C1-8)alkylthio, (C2-8)alkenyl, or (C2-8)alkynyl;
• R5 is hydrogen, cyano, halogen, (C1-8)alkyl, halogen-(C1-8)alkyl, (C1-8)alkoxy, halogen-(C1-8)alkoxy, (C1-8e)alkylthio, halogen-(C1-8)alkylthio, (C1-8)alkoxy-(C1-8)alkyl, (C1-8)alkoxy-(C1-8)alkoxy, (C1-8)alkoxy-(C1-8)alkylthio, (C1-8)alkylthio-(C1-8)alkyl, (C1-8)alkylthio-(C1-8)alkoxy, (C1-8)alkylthio-(C1-8)alkylthio, (C2-8)alkenyl, or (C2-8)alkynyl;
• or
• R4 and R5, taken together, are —C(H)═C(H)—C(H)═C(H)— or a (C1-8)alkylene group, in which (C1-8)alkylene group 1 or 2 —CH2— ring members are optionally replaced with hetero ring members independently selected from the group, consisting of —N(H)—, —[(C1-8)alkyl]-, —O—, —S—, —S(═O)— or —S(═O)2—;
• R6 is (C1-8)alkyl, halogen-(C1-8)alkyl, hydroxy-(C1-8)alkyl, (C1-8)alkoxy-(C1-8)alkyl, mercapto-(C1-8)alkyl, (C1-8)alkylthio-(C1-8)alkyl, amino-(C1-8)alkyl, N-(C1-4)alkyl-amino-(C1-8)alkyl, N,N-di(C1-4)alkyl-amino-(C1-8)alkyl, (C2-8)alkenyl, or (C2-8)alkynyl;
• or
• R5 and R6, taken together, are a (C1-4)alkylene group, in which (C1-4)alkylene group 1 -CH2— ring member is optionally replaced with a hetero ring member independently selected from the group, consisting of —N(H)—, —N[(C1-4)alkyl]-, —O—, —S—, —S(═O)— or —S(═O)2—;
• E1 is —C(R7)(R8)—, or —C(R7)(R8)—C(R9)(R10)—;
• E2 is —C(R11)(R12)—, or —C(R11)(R12)—C(R13)(R14)—;
• either
• each of R7 and R8 is independently selected from the group, consisting of hydrogen, cyano, halogen, (C1-8)alkyl, halogen-(C1-8)alkyl, (C1-8)alkoxy-(C1-8)alkyl and (C1-8)alkylthio-(C1-8)alkyl;
• or
• R7 and R8, taken together, are oxo or —CH2—CH2—;
• either
• each of R9 and R10 is independently selected from the group, consisting of hydrogen, cyano, halogen, (C1-8)alkyl, halogen-(C1-8)alkyl, (C1-8)alkoxy-(C1-8)alkyl and (C1-8)alkylthio-(C1-8)alkyl;
• or
• R9 and R10, taken together, are oxo or —CH2—CH2—;
• either
• each of R11 and R12 is independently selected from the group, consisting of hydrogen, cyano, halogen, (C1-8)alkyl, halogen-(C1-8)alkyl, (C1-8)alkoxy-(C1-8)alkyl and (C1-8)alkylthio-(C1-8)alkyl;
• or
• R11 and R12, taken together, are oxo or —CR15R16—CR17R18—
• wherein R15, R16, R17 and R18 are independently selected from hydrogen and fluoro;
• and
• either
• each of R13 and R14 is independently selected from the group, consisting of hydrogen, cyano, halogen, (C1-8)alkyl, halogen-(C1-8)alkyl, (C1-8)alkoxy-(C1-8)alkyl and (C1-8)alkylthio-(C1-8)alkyl;
• or
• R13 and R14, taken together, are oxo or —CH2—CH2—.