Substituted oxa-diaza-spiro-[5.5]-undecanone derivatives and their use as neurokinin antagonists

A compound according to Formula (I)

• pharmaceutically acceptable acid or base addition salts thereof, stereochemically isomeric forms thereof, N-oxide form thereof, or prodrug thereof, wherein:
• R2 is Ar2, Ar2-alkyl, di(Ar2)alkyl;
• X is a covalent bond or a bivalent radical of formula —O—, —S— or —NR3—;
• Q is O or NR3;
• each R3 is independently hydrogen or alkyl;
• R1 is Ar1, Ar1-alkyl or di(Ar1)-alkyl;
• n is an integer, equal to 0, 1 or 2;
• m is an integer, equal to 1 or 2, provided that if m is 2, then n is 1;
• Z is a covalent bond or a bivalent radical of formula —CH2— or >C(═O);
• A1, A2, A3 and A4 are each independently CH2CH2—, —C(═O)O— or —OC(═O)—, provided that at least one of —C(═O)O— or —OC(═O)— is selected and that ═O is in an alpha-position relative to the N-atom;
• each Alk is independently 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 at least one carbon atom with at least one phenyl, halo, cyano, hydroxy, formyl or amino radical;
• Y is a covalent bond or a bivalent radical of formula —C(═O)—, —SO2—, —C(═CH—R)— or —C(═N—R)—, wherein R is H, CN or nitro;
• L is hydrogen, alkyl, alkenyl, alkyloxy, alkyloxyalkyloxy, alkylcarbonyloxy, alkyloxycarbonyl, mono- or di(alkyl)amino, mono- or di(alkyloxycarbonyl)amino, mono- or di(alkylcarbonyl)amino, mono- or di(Ar3)amino, mono- or di(Ar3alkyl)amino, mono- or di(Het2)amino, mono- or di(Het2alkyl)amino, alkylsulfonyl, norbornyl, adamantyl, tricycloundecyl, Ar3, Ar3-oxy, Ar3-carbonyl, Het2, Het-oxy, Het2-carbonyl or mono- or di(Het2-carbonyl)amino;
• Ar1 is phenyl, optionally substituted with 1, 2 or 3 substituents, each independently halo, alkyl, cyano, aminocarbonyl or alkyloxy;
• Ar2 is naphthalenyl or phenyl, each optionally substituted with 1, 2 or 3 substituents, each independently halo, nitro, amino, mono- or di(alkyl)amino, cyano, alkyl, hydroxy, alkyloxy, carboxyl, alkyloxycarbonyl, aminocarbonyl or mono- or di(alkyl)aminocarbonyl;
• Ar3 is naphthalenyl or phenyl, optionally substituted with 1, 2 or 3 substituents, each independently alkyloxy, alkylcarbonylamino, methanesulfonyl, Ar1carbonyloxyalkyl, Ar1alkyloxycarbonyl, Ar1alkyloxyalkyl, alkyl, halo, hydroxy, pyridinyl, morpholinyl, pyrrolyl, pyrrolidinyl, imidazo[1,2-a]pyridinyl, morpholinylcarbonyl, pyrrolidinylcarbonyl, amino or cyano;
• Het2 is a monocyclic heterocyclic radical that is pyrrolidinyl, dihydro-2H-pyranyl, pyranyl, dioxolyl, imidazolidinyl, tetrahydropyridinyl, tetrahydropyrimidinyl, pyrazolidinyl, piperidinyl, morpholinyl, dithianyl, thiomorpholinyl, piperazinyl, imidazolidinyl, tetrahydrofuranyl, 2H-pyrrolyl, pyrrolinyl, imidazolinyl, pyrazolinyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, furanyl, thienyl, oxazolyl, dioxazolyl, oxazolidinyl, isoxazolyl, thiazolyl, thiadiazolyl, isothiazolyl, pyridinyl, 1H-pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, triazinyl or tetrazolyl;
• or a bicyclic heterocyclic radical that is 2,3-dihydro-benzo[1,4]dioxine, octahydro-benzo[1,4]dioxine, octabicycloheptyl, benzopiperidinyl, quinolinyl, quinoxalinyl, indolyl, isoindolyl, chromanyl, benzimidazolyl, imidazo[1,2-a]pyridinyl, benzoxazolyl, benzodioxolyl, benzisoxazolyl, benzoxadiazolyl, benzothiazolyl, benzisothiazolyl, benzofuranyl, dihydroisobenzofuranyl, or benzothienyl;
• wherein each mono-, or bicyclic heterocyclic radical is optionally substituted on any atom with at least one radical that is Ar1, Ar1alkyl, Ar1alkyloxyalkyl, halo, hydroxy, alkyl, piperidinyl, pyrrolyl, thienyl, oxo, alkyloxy, alkylcarbonyl, Ar1carbonyl, mono- or di(alkyl)aminoalkyl, alkyloxyalkyl or alkyloxycarbonyl;
• alkyl is a straight or a branched 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 at least one carbon atom with at least one radical that is phenyl, halo, trihalomethyl, aminocarbonyl, methyl, ethyl, propyl, isopropyl, t-butyl, cyano, oxo, hydroxy, formyl or amino;
• and
• alkenyl is a straight or branched unsaturated hydrocarbon radical having from 1 to 6 carbon atoms and having at least one unsaturated bond;
• or a cyclic unsaturated hydrocarbon radical having from 3 to 6 carbon atoms and having at least one unsaturated bond;
• each hydrocarbon radical optionally substituted on at least one carbon atom with at least one radical that is phenyl, halo, cyano, oxo, hydroxy, formyl or amino.