1-[1-(hetero) aryl-1-perhydroxyalkylmethyl]-piperazine compounds, process for their preparation and pharmaceutical compositions containing them

A process for the preparation of a compound corresponding to formula I:

• 18
• wherein
• A is naphthyl, phenyl optionally substituted by hydroxy, mono- or bicyclic heteroaryl or C3-6-alkenyl optionally substituted by phenyl,
• Z is a subgroup corresponding to the formula
• 19
• wherein
• R1 is hydrogen or lower alkanoyl, or together with another substituent, selected from the group consisting of R2, R3, R4 and R5, may form a 5- or 6-member ring bridged by carbonyl, thiocarbonyl or by methylene optionally substituted by lower alkyl or C4-5-alkylene,
• R2 is hydrogen or lower alkanoyl, or together with another substituent, selected from the group consisting of R1, R3, R4 and R5, may form a 5- or 6-member ring bridged by carbonyl, thiocarbonyl or by methylene optionally substituted by lower alkyl or C4-5-alkylene,
• R3 is hydrogen or lower alkanoyl, or together with another substituent, selected from the group consisting of R1, R2, R4 and R5, may form a 5- or 6-member ring bridged by carbonyl, thiocarbonyl or by methylene optionally substituted by lower alkyl or C4-5-alkylene,
• R4 is hydrogen or lower alkanoyl, or together with another substituent, selected from the group consisting of R1, R2, R3 and R5, may form a 5- or 6-member ring bridged by carbonyl, thiocarbonyl or by methylene optionally substituted by lower alkyl or C4-5-alkylene,
• R5 is hydrogen or lower alkanoyl, or together with another substituent, selected from the group consisting of R1, R2, R3 and R4, may form a 5- or 6-member ring bridged by carbonyl, thiocarbonyl or by methylene optionally substituted by lower alkyl or C4-5-alkylene,
• k is 0 or 1,
• l is 0 or 1,
• m is 0 or 1 and
• n is 0 or 1,
• R6 is halogen or hydrogen, and
• R7 is halogen or hydrogen,
• or a physiologically compatible acid addition salt thereof, said process comprising reacting a compound of formula II:
• 20
• wherein R6 and R7 have the above meanings, with a compound of formula III:
• A—B(OH)2 III
• wherein A has the above meaning, and with a compound of formula IV:
• 21
• wherein R1, R2, R3, R4, R5, k, l, m und n have the above meanings, and
• optionally acylating a resulting compound of Formula I, wherein at least one substituent selected from R1, R2, R3, R4 and R5 is hydrogen, in the subgroup Z by reacting with a compound corresponding to formula VIII:
• R8—COOH (VIII)
• wherein R8 is a straight-chain or branched alkyl with 1 to 3 carbon atoms, or
• optionally carbonylating or thiocarbonylating a resulting compound of Formula I, wherein at least two substituents selected from R1, R2, R3, R4 and R5 are hydrogen, in the subgroup Z by reacting the compound of formula I with a reactive carbonyl- or thiocarbonyl synthesis equivalent, or optionally converting a resulting compound of Formula I, wherein at least two substituents, selected from R1, R2, R3, R4 and R5 are hydrogen, to a 5- or 6-member ring derivative bridged by methylene and optionally substituted by lower alkyl or C4-5-alkylene by reacting the compound of Formula I in the subgroup Z with a di-lower alkylketone or a C5-6-cycloalkylketone, and
• optionally converting compound of Formula I into a corresponding acid addition salt, or
• optionally converting an acid addition salt into a free compound of Formula I.

A compound corresponding to formula II:

• 22
• wherein
• R6 is halogen or hydrogen, and
• R7 is halogen or hydrogen.