Substituted 1,4,-di-piperidin-4-yl-piperazine derivatives and their use as neurokinin antagonists

A compound according to the general Formula (I)

• the pharmaceutically acceptable acid or base addition salts thereof, the stereochemically isomeric forms thereof, wherein:
• n is an integer equal to 1;
• m is an integer equal to 1;
• p is an integer equal to 1;
• Q is O or NR3;
• X is a covalent bond or a radical of formula —O—, —S— or —NR3—;
• each R3 independently from each other, is hydrogen or alkyl;
• each R1 independently from each other, is selected from the group consisting of Ar1, Ar1-alkyl and di(Ar1)-alkyl;
• q is an integer equal to 0 or 1;
• R2 is selected from the group consisting of alkyl, Ar2, Ar2-alkyl, Het1 or Het1-alkyl;
• Y is a covalent bond or a bivalent radical of formula —C(═O)— or —SO2—;
• each Alk represents, independently from each other, a covalent bond;
• a bivalent straight or branched, saturated or unsaturated hydrocarbon radical having from 1 to 6 carbon atoms;
• or a cyclic saturated or unsaturated hydrocarbon radical having from 3 to 6 carbon atoms;
• each radical optionally substituted on one or more carbon atoms with one or more alkyl, phenyl, halo, cyano, hydroxy, formyl and amino radicals;
• L is selected from the group of hydrogen, alkyloxy, Ar3-oxy, alkyloxycarbonyl, mono- and di(alkyl)amino, mono- and di(Ar3)amino, mono- and di(alkyloxycarbonyl)amino, Ar3, Ar3-carbonyl, Het2 and Het2-carbonyl;
• Ar1 is phenyl, optionally substituted with 1, 2 or 3 substituents each independently from each other selected from the group consisting of halo, alkyl, cyano, aminocarbonyl and alkyloxy;
• Ar2 is naphthalenyl or phenyl, each optionally substituted with 1, 2 or 3 substituents, each independently from each other, selected from the group consisting of halo, nitro, amino, mono- and di(alkyl)amino, cyano, alkyl, hydroxy, alkyloxy, carboxyl, alkyloxycarbonyl, aminocarbonyl and mono- and di(alkyl)aminocarbonyl;
• Ar3 is naphthalenyl or phenyl, optionally substituted with 1, 2 or 3 substituents each independently from each other selected from the group consisting of alkyloxy, alkyl, halo, hydroxy, pyridinyl, morpholinyl, pyrrolidinyl, imidazo[1,2-α]pyridinyl, morpholinylcarbonyl, pyrrolidinylcarbonyl, amino and cyano;
• Het1 is a monocyclic heterocyclic radical selected from the group consisting of pyrrolyl, pyrazolyl, imidazolyl, furanyl, thienyl, oxazolyl, isoxazolyl, thiazolyl, thiadiazolyl, isothiazolyl, pyridinyl, pyrimidinyl, pyrazinyl and pyridazinyl;
• or a bicyclic heterocyclic radical selected from the group of quinolinyl, quinoxalinyl, indolyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzothiazolyl, benzisothiazolyl, benzofuranyl and benzothienyl;
• each heterocyclic radical may optionally be substituted on any atom by a radical selected from the group consisting of halo and alkyl;
• Het2 is a monocyclic heterocyclic radical selected from the group consisting of pyrrolidinyl, dioxolyl, imidazolidinyl, pyrrazolidinyl, piperidinyl, morpholinyl, dithianyl, thiomorpholinyl, piperazinyl, imidazolidinyl, tetrahydrofuranyl, 2H-pyrrolyl, pyrrolinyl, imidazolinyl, pyrrazolinyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, furanyl, thienyl, oxazolyl, isoxazolyl, thiazolyl, thiadiazolyl, isothiazolyl, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl and triazinyl;
• or a bicyclic heterocyclic radical selected from the group consisting of benzopiperidinyl, quinolinyl, quinoxalinyl, indolyl, isoindolyl, chromenyl, benzimidazolyl, imidazo[1,2-α]pyridinyl, benzoxazolyl, benzisoxazolyl, benzothiazolyl, benzisothiazolyl, benzofuranyl and benzothienyl;
• each radical optionally substituted with one or more radicals selected from the group consisting of Ar1, Ar1alkyl, halo, hydroxy, alkyl, piperidinyl, pyrrolyl, thienyl, oxo, alkyloxy, alkyloxyalkyl and alkyloxycarbonyl;
• and
• alkyl is a straight or branched saturated hydrocarbon radical having from 1 to 6 carbon atoms or a cyclic saturated hydrocarbon radicals having from 3 to 6 carbon atoms;
• optionally substituted on one or more carbon atoms with one or more radicals selected from the group consisting of phenyl, halo, cyano, oxo, hydroxy, formyl and amino radicals.