Substituted diaza-spiro-[4.5]-decane derivatives and their use as neurokinin antagonists

A process for preparing a compound according to Formula (I):

• the pharmaceutically acceptable acid or base addition salts thereof, the stereochemic ally isomeric forms thereof, or the N-oxide forms thereof wherein:
• R2 is Ar2;
• X is a covalent bond;
• Q is O;
• R1 is Ar1-alkyl;
• n is an integer, equal to 1 ;
• m is an integer, equal to 1 ;
• Z is a covalent bond;
• j, k, p, q are integers, independently from each other, equal to 0, 1, 2, 3 or 4;
• provided that (j+k) and (p+q) are each equal to 3 or 4 and provided that when (j+k) is equal to 3, then (p+q) is equal to 4;
• or when (j+k) is equal to 4 then (p+q) is equal to 3;
• t=0 or 2;
• and if t=2, each T is taken together to form a radical of formula ═CH—CH═CH—CH═;
• each Alk represents, independently from each other, a covalent bond;
• a bivalent straight saturated hydrocarbon radical having from 1 to 6 carbon atoms;
• Y is a bivalent radical of formula —C(═O)— or —SO2—;
• L is alkyl, alkyloxy, Ar3, or Het2;
• Ar1 is phenyl;
• Ar2 is phenyl substituted with 2 alkyl substituents;
• Ar3 is phenyl, optionally substituted with 1 substituent that is alkyl or halo;
• Het2 is a monocyclic heterocyclic radical that is tetrahydrofuranyl;
• furanyl, or thienyl;
• and
• alkyl is a straight saturated hydrocarbon radical having from 1 to 6 carbon atoms or a cyclic saturated hydrocarbon radical having from 3 to 6 carbon atoms;
• each hydrocarbon radical optionally substituted on one or more carbon atoms with at least one halo;
• comprising
• a) reductively N-alkylating an intermediate compound of Formula (II) with an intermediate compound of Formula (III) to obtain a final compound according to Formula (Ia), in a reaction-inert solvent and optionally in the presence of a reducing agent;
• or b) reductively N-alkylating an intermediate compound of Formula (IV) with an intermediate compound of Formula (III) to obtain a final compound according to Formula (Ib), in a reaction-inert solvent and optionally in the presence of a reducing agent;
• or c) reacting an intermediate compound of Formula (III) with a carboxylic acid compound of Formula (V) to obtain a final compound according to Formula (Ic), in a reaction-inert solvent and optionally in the presence of a base;
• and (d) optionally, converting compounds of Formula (I), into each other following transformation, and optionally, converting the compounds of Formula (I), into a therapeutically active non-toxic acid addition salt by treatment with an acid, or into a therapeutically active non-toxic base addition salt by treatment with a base, or conversely, converting the acid addition salt form into the free base by treatment with alkali, or converting the base addition salt into the free acid by treatment with acid;
• and, optionally, preparing stereochemically isomeric forms or N-oxide forms thereof.